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Sample records for sustained release d-amphetamine

  1. Cannabinoids negatively modulate striatal glutamate and dopamine release and behavioural output of acute D-amphetamine.

    Science.gov (United States)

    Polissidis, A; Chouliara, O; Galanopoulos, A; Naxakis, G; Papahatjis, D; Papadopoulou-Daifoti, Z; Antoniou, K

    2014-08-15

    The cannabinoid system plays a regulatory role in neurotransmission and is involved in the central actions of psychostimulants. This complex interaction between the cannabinoid system and psychostimulants represents a potential pharmacological target for psychosis and addiction. However, most studies have focused on cocaine, therefore, it is unclear whether these findings can be extended to other psychostimulants such as the amphetamines. The present study investigated the effects of WIN55,212-2, a synthetic cannabinoid and SR141716A, a CB1 receptor antagonist, on D-amphetamine-induced locomotor activity and extracellular dopamine and glutamate release in the striatum. Rats were either observed for locomotor activity or glutamate and dopamine neurotransmitter release in the striatum using in vivo microdialysis following intraperitoneal co-administration of D-amphetamine with WIN55,212-2 or SR141716A. Our results demonstrated that d-amphetamine per se induced hyperlocomotion and enhanced dopamine and glutamate release, as expected. WIN55,212-2 dampened these effects when co-administered with d-amphetamine, while alone it displayed its characteristic biphasic motor profile coupled with increases in dopamine and decreases in glutamate release. SR141716A at high doses reduced D-amphetamine-induced hyperlocomotion and completely reversed enhanced dopamine and glutamate release but alone had no effect. These findings validate the capacity of the cannabinoid system to modulate amphetamine-induced behaviour and its neurochemical output, in a state-dependent manner, providing insight into aspects of the neurobiological substrate that underlies amphetamines' psychotogenic and addictive properties. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Modafinil, d-amphetamine and placebo during 64 hours of sustained mental work. I. Effects on mood, fatigue, cognitive performance and body temperature.

    Science.gov (United States)

    Pigeau; Naitoh; Buguet; McCann; Baranski; Taylor; Thompson; MacK

    1995-12-01

    Modafinil is an alerting substance that is considered safer than amphetamine with fewer side effects. Although modafinil has been used successfully to treat narcolepsy, relatively little is known about its ability to ameliorate fatigue and declines in mental performance due to sleep deprivation (SD) in a normal population. Forty-one military subjects received either 300 mg of modafinil, 20 mg of d-amphetamine, or placebo on 3 separate occasions during 64 hours of continuous cognitive work and sleep loss. Three drug treatments were given: at 23.30 hours and 05.30 hours during the first and second SD nights, respectively, and once at 15.30 hours during the third day of continuous work. Subjective estimates of mood, fatigue and sleepiness, as well as objective measures of reaction time, logical reasoning and short-term memory clearly showed better performance with both modafinil and amphetamine relative to placebo. Both modafinil and amphetamine maintained or increased body temperature compared to the natural circadian cycle observed in the placebo group. Also, from subject debriefs at the end of the study, modafinil elicited fewer side-effects than amphetamine, although more than the placebo group. Modafinil appears to be a good alternative to amphetamine for counteracting the debilitating mood and cognitive effects of sleep loss during sustained operations.

  3. Preclinical pharmacokinetics, pharmacology and toxicology of lisdexamfetamine: a novel d-amphetamine pro-drug.

    Science.gov (United States)

    Hutson, Peter H; Pennick, Michael; Secker, Roger

    2014-12-01

    Lisdexamfetamine dimesylate (LDX) is a novel pro-drug of d-amphetamine that is currently used for the treatment of attention-deficit/hyperactivity disorder in children aged ≥ 6 years and adults. LDX is enzymatically cleaved to form d-amphetamine following contact with red blood cells, which reduces the rate of appearance and magnitude of d-amphetamine concentration in the blood and hence the brain when compared with immediate-release d-amphetamine at equimolar doses. Thus, the increase of striatal dopamine efflux and subsequent increase of locomotor activity following d-amphetamine is less prominent and slower to attain maximal effect following an equimolar dose of LDX. Furthermore, unlike d-amphetamine, the pharmacodynamic effects of LDX are independent of the route of administration underlining the requirement to be hydrolyzed by contact with red blood cells. It is conceivable that these pharmacokinetic and pharmacodynamic differences may impact the psychostimulant properties of LDX in the clinic. This article reviews the preclinical pharmacokinetics, pharmacology, and toxicology of LDX. This article is part of the Special Issue entitled 'CNS Stimulants'. Copyright © 2014. Published by Elsevier Ltd.

  4. Female rats that rapidly acquire a d-amphetamine discrimination generalize more to d-amphetamine.

    Science.gov (United States)

    Tomie, A; Mosakowski, E M

    1996-08-01

    Female Long-Evans rats were trained to discriminate d-amphetamine (0.8 mg/kg) vs. saline in a food-reinforced two-lever operant task. Fifteen rats (fast group) acquired the discrimination rapidly, achieving criterion (eight correct choices within ten sessions) during the first 10 sessions (mean sessions to criterion = 10.0). The remaining eight rats (slow group) made at least three errors during the first 10 sessions and required additional drug discrimination training to achieve criterion (mean sessions to criterion = 15.9). When a rat had completed a minimum of 30 two-lever discrimination training sessions and, in addition, provided 10 correct choices within 10 sessions, generalization testing with lower doses of d-amphetamine was initiated. The fast group made more d-amphetamine-appropriate choices during the generalization test and generalized more to the 0.2 mg/kg d-amphetamine test dose than did the slow group, though the number of training sessions prior to generalization testing was comparable across groups. Results suggest that when the training drug is easily discriminated, fast learners generalize more, even when groups receive comparable amounts of training prior to generalization testing, and this effect is observed in female rats.

  5. Individual differences in timing of peak positive subjective responses to d-amphetamine: Relationship to pharmacokinetics and physiology.

    Science.gov (United States)

    Smith, Christopher T; Weafer, Jessica; Cowan, Ronald L; Kessler, Robert M; Palmer, Abraham A; de Wit, Harriet; Zald, David H

    2016-04-01

    Rate of delivery of psychostimulants has been associated with their positive euphoric effects and potential addiction liability. However, information on individual differences in onset of d-amphetamine's effects remains scarce. We examined individual differences in the time to peak subjective and physiological effects and the pharmacokinetics/pharmacodynamics of oral d-amphetamine. We considered two independent studies that used different dosing regimens where subjects completed the drug effects questionnaire at multiple time points post d-amphetamine. Based on the observation of distinct individual differences in time course of drug effects questionnaire "feel", "high", and "like" ratings (DEQH+L+F) in Study 1, subjects in both studies were categorized as early peak responders (peak within 60 minutes), late peak responders (peak > 60 minutes) or nonresponders; 20-25% of participants were categorized as early peak responders, 50-55% as late peak responders and 20-30% as nonresponders. Physiological (both studies) and plasma d-amphetamine (Study 1) were compared among these groups. Early peak responders exhibited an earlier rise in plasma d-amphetamine levels and more sustained elevation in heart rate compared to late peak responders. The present data illustrate the presence of significant individual differences in the temporal pattern of responses to oral d-amphetamine, which may contribute to heightened abuse potential. © The Author(s) 2016.

  6. Combined effects of modafinil and d-amphetamine in male Sprague-Dawley rats trained to discriminate d-amphetamine.

    Science.gov (United States)

    Quisenberry, Amanda J; Prisinzano, Thomas; Baker, Lisa E

    2013-09-01

    Modafinil is a novel wake-promoting drug with FDA approval for the treatment of sleep-related disorders that has recently been investigated as a potential agonist replacement therapy for psychostimulant dependence. Previous research in animals and humans indicates modafinil has a lower abuse liability than traditional psychostimulants, although few studies have carefully assessed modafinil's stimulus properties in combination with other psychostimulants. The current study trained male Sprague-Dawley rats to discriminate subcutaneous injections of 0.3 mg/kg (n=8) or 1.0 mg/kg d-amphetamine (n=8) from saline under an FR 20 schedule of food reinforcement and substitution tests were administered with d-amphetamine (0.03-1.0 mg/kg, s.c.), modafinil (32-256 mg/kg, i.g.), and a low modafinil dose (32 mg/kg, i.g.) in combination with d-amphetamine (0.03-1.0 mg/kg, s.c.) to determine if these drugs have additive effects. The selective D2 dopamine agonist, PNU-91356A, was also tested as a positive control and ethanol and morphine were tested as negative controls. Results indicate that modafinil produced dose-dependent and statistically significant d-amphetamine-lever responding in both groups and nearly complete substitution in animals trained to discriminate 1.0 mg/kg d-amphetamine. Modafinil pretreatment slightly increased the discrimination of low d-amphetamine doses in animals trained to discriminate 0.3 mg/kg d-amphetamine. These results support previous findings that modafinil and d-amphetamine may have additive effects. In consideration of recent interests in modafinil as an agonist treatment for psychostimulant dependence, additional preclinical investigations utilizing other methodologies to examine modafinil in combination with other stimulants, such as behavioral sensitization paradigms or drug self-administration, may be of interest. © 2013.

  7. Early Ontogeny of D-Amphetamine-Induced One-Trial Behavioral Sensitization

    Science.gov (United States)

    McDougall, Sanders A.; Nuqui, Charlotte M.; Quiroz, Anthony T.; Martinez, Carrissa M.

    2013-01-01

    The early ontogeny of D-amphetamine-induced one-trial behavioral sensitization was characterized using male and female preweanling and preadolescent rats. In Experiment 1, rats were injected with saline or D-amphetamine (1, 4, or 8 mg/kg) in activity chambers or the home cage on postnatal day (PD) 12, PD 16, PD 20, or PD 24. One day later, rats were challenged with either 0.5 or 2 mg/kg D-amphetamine and distance traveled was measured in activity chambers for 120 min. In Experiment 2, saline or D-amphetamine was administered in activity chambers on PD 24, while a challenge injection of D-amphetamine (0.25–4 mg/kg) was given on PD 25. At younger ages (PD 13 and PD 17), a strong sensitized response was evident on the test day regardless of whether rats were pretreated with D-amphetamine (4 or 8 mg/kg) before being placed in the activity chamber or 30 min after being returned to the home cage. Rats did not display D-amphetamine-induced behavioral sensitization on PD 21, nor was context-dependent sensitization apparent on PD 25 even when a broad dose range of D-amphetamine was used. When low doses of D-amphetamine were administered on the pretreatment and test days (1 and 0.5 mg/kg, respectively), sensitized responding was not evident at any age. In summary, D-amphetamine-induced one-trial behavioral sensitization was only apparent within a narrow developmental window during early ontogeny. This ontogenetic pattern of sensitized responding is similar to the one produced by methamphetamine and distinct from the pattern produced by cocaine. The unique sensitization profiles resulting from repeated D-amphetamine and cocaine treatment may be a consequence of their different mechanisms of action. PMID:23360956

  8. Effects of d-amphetamine upon psychosocial stress responses.

    Science.gov (United States)

    Childs, Emma; Bershad, Anya K; de Wit, Harriet

    2016-07-01

    Psychostimulant drugs alter the salience of stimuli in both laboratory animals and humans. In animals, stimulants increase rates of responding to conditioned incentive stimuli, and in humans, amphetamine increases positive ratings of emotional images. However, the effects of stimulants on real-life emotional events have not been studied in humans. In this study, we examined the effect of d-amphetamine on responses to acute psychosocial stress using a public speaking task. Healthy volunteers (N=56) participated in two experimental sessions, one with a psychosocial stressor (the Trier Social Stress Test) and one with a non-stressful control task. They were randomly assigned to receive d-amphetamine (5 mg n=18, 10 mg n=20) or placebo (n=18) on both sessions under double blind conditions. Salivary cortisol, subjective mood, and vital signs were measured at regular intervals during the session. Subjects also provided cognitive appraisals of the tasks before and after their performances. Amphetamine produced its expected mood and physiological effects, and the Trier Social Stress Test produced its expected effects on cortisol and mood. Although neither dose of amphetamine altered cardiovascular or hormonal responses to stress, amphetamine (10 mg) increased participants' pre-task appraisals of how challenging the task would be, and it increased post-task ratings of self-efficacy. Paradoxically, it also increased ratings of how stressful the task was, and prolonged aversive emotional responses. These findings suggest that amphetamine differentially affects stress response components: it may increase participants' appraisals of self-efficacy without dampening the direct emotional or physiological responses to the stress. © The Author(s) 2016.

  9. Effect of D-amphetamine on inhibition and motor planning as a function of baseline performance.

    Science.gov (United States)

    Allman, Ava-Ann; Benkelfat, Chawki; Durand, France; Sibon, Igor; Dagher, Alain; Leyton, Marco; Baker, Glen B; O'Driscoll, Gillian A

    2010-09-01

    Baseline performance has been reported to predict dopamine (DA) effects on working memory, following an inverted-U pattern. This pattern may hold true for other executive functions that are DA-sensitive. The objective of this study is to investigate the effect of D: -amphetamine, an indirect DA agonist, on two other putatively DA-sensitive executive functions, inhibition and motor planning, as a function of baseline performance. Participants with no prior stimulant exposure participated in a double-blind crossover study of a single dose of 0.3 mg/kg, p.o. of D: -amphetamine and placebo. Participants were divided into high and low groups, based on their performance on the antisaccade and predictive saccade tasks on the baseline day. Executive functions, mood states, heart rate and blood pressure were assessed before (T0) and after drug administration, at 1.5 (T1), 2.5 (T2) and 3.5 h (T3) post-drug. Antisaccade errors decreased with D: -amphetamine irrespective of baseline performance (p = 0.025). For antisaccade latency, participants who generated short-latency antisaccades at baseline had longer latencies on D: -amphetamine than placebo, while those with long-latency antisaccades at baseline had shorter latencies on D: -amphetamine than placebo (drug x group, p = 0.04). D: -amphetamine did not affect motor planning. Ratings of mood improved on D: -amphetamine (p < 0.001). Magnitude of D: -amphetamine-induced changes in elation was related to baseline reaction time variability. D: -amphetamine reduced antisaccade error rates in healthy controls, replicating and extending findings with DA agonists in clinical populations. D: -amphetamine had baseline-dependent effects on antisaccade latency, consistent with an inverted-U relationship between performance and DA activity.

  10. Pharmacokinetics and Pharmacodynamics of Lisdexamfetamine Compared with D-Amphetamine in Healthy Subjects

    Directory of Open Access Journals (Sweden)

    Patrick C. Dolder

    2017-09-01

    Full Text Available Rationale: Lisdexamfetamine is a prodrug of D-amphetamine used for the treatment of attention-deficit/hyperactivity disorder (ADHD. Lisdexamfetamine is thought to have a prolonged pharmacokinetic profile compared with oral D-amphetamine, possibly associated with lower drug liking and a lower risk of oral misuse. However, differences in the pharmacokinetics and pharmacodynamics of lisdexamfetamine and D-amphetamine have not been directly compared.Methods: Equimolar doses of D-amphetamine (40 mg and lisdexamfetamine (100 mg, and placebo were administered in 24 healthy subjects in a randomized, double-blind, placebo-controlled, cross-over study. Plasma concentrations of amphetamine, subjective effects, and vital signs were repeatedly assessed. The pharmacokinetic parameters were determined using compartmental modeling.Results: The increase in plasma concentrations of amphetamine had a 0.6 ± 0.6 h (mean ± SD longer lag time and reached peak levels 1.1 ± 1.5 h later after lisdexamfetamine administration compared with D-amphetamine administration, but no differences in maximal concentrations or total exposure (AUC were found between the two treatments. Consistent with the pharmacokinetics, the subjective and cardiovascular stimulant effects of lisdexamfetamine also occurred later compared with D-amphetamine. However, no differences in peak ratings of potentially abuse-related subjective drug effects (e.g., drug liking, drug high, stimulation, happy, well-being, and self-confidence were observed after lisdexamfetamine administration compared with D-amphetamine administration. Lisdexamfetamine and D-amphetamine also produced similar peak increases in mean arterial blood pressure, heart rate, body temperature, pupil size, and adverse effects.Conclusion: The pharmacokinetics and pharmacodynamics of lisdexamfetamine are similar to D-amphetamine administered 1h later. Lisdexamfetamine is likely associated with a similar risk of oral abuse as D-amphetamine

  11. Formulation and Characterization of Sustained Release Floating ...

    African Journals Online (AJOL)

    Conclusion: Microballoons is a potential suitable delivery system for sustained release of metformin hydrochloride with improved bioavailability when compared with conventional dosage forms of the drug. Keywords: Gastroretentive drug delivery system (GDDS), Solvent evaporation and diffusion method, Higuchi, ...

  12. Preparation and Characterization of Sustained Release Matrix ...

    African Journals Online (AJOL)

    Purpose: To formulate matrix type sustained-release (SR) tablets of tizanidine hydrochloride (TH) for prolonged drug release and improvement in motor activity after spinal injuries. Methods: Matrix tablets were prepared by the wet granulation method using four polymers (hydroxyl propyl methyl cellulose [HPMC] K 100, ethyl ...

  13. Development of sustained release tablets containing solid ...

    African Journals Online (AJOL)

    Sustained release tablets containing solid dispersions granules of a poorly water soluble drug were prepared to investigate the controlled release of the drug. Baclofen was chosen because of its poor water solubility and short elimination half-life. Poloxamer 188 and PEG 6000 were used as solid dispersion carrier.

  14. Methamphetamine self-administration in humans during D-amphetamine maintenance.

    Science.gov (United States)

    Pike, Erika; Stoops, William W; Hays, Lon R; Glaser, Paul E A; Rush, Craig R

    2014-12-01

    Agonist replacement may be a viable treatment approach for managing stimulant use disorders. This study sought to determine the effects of D-amphetamine maintenance on methamphetamine self-administration in stimulant using human participants. We predicted that D-amphetamine maintenance would reduce methamphetamine self-administration. Eight participants completed the protocol, which tested 2 D-amphetamine maintenance conditions in counterbalanced order (0 and 40 mg/d). Participants completed 4 experimental sessions under each maintenance condition in which they first sampled 1 of 4 doses of intranasal methamphetamine (0, 10, 20, or 30 mg). Participants then had the opportunity to respond on a computerized progressive-ratio task to earn portions of the sampled methamphetamine dose. Subject-rated drug effect and physiological measures were completed at regular intervals prior to and after sampling methamphetamine. Methamphetamine was self-administered as an orderly function of dose regardless of the maintenance condition. Methamphetamine produced prototypical subject-rated effects on 12 items of the drug-effects questionnaires, 8 of which were attenuated by D-amphetamine maintenance (eg, increased ratings were attenuated on items such as Any Effect, Like Drug, and Willing to Take Again on the Drug Effect Questionnaire). Methamphetamine produced significant increases in systolic blood pressure, which were attenuated by D-amphetamine maintenance compared to placebo maintenance. Methamphetamine was well tolerated during D-amphetamine maintenance and no adverse events occurred. Although D-amphetamine attenuated some subject-rated effects of methamphetamine, the self-administration results are concordant with those of clinical trials showing that D-amphetamine did not reduce methamphetamine use. Unique pharmacological approaches may be needed for treating amphetamine use disorders.

  15. Contextual conditioning enhances the psychostimulant and incentive properties of d-amphetamine in humans.

    Science.gov (United States)

    Childs, Emma; de Wit, Harriet

    2013-11-01

    Learned associations between drugs and the places they are used are critical to the development of drug addiction. Contextual conditioning has long been studied in animals as an indirect measure of drug reward, but little is known about the process in humans. Here, we investigated de novo contextual conditioning with d-amphetamine in healthy humans (n = 34). Volunteers underwent four conditioning sessions conducted in two testing rooms with double-blind, alternating d-amphetamine (20 mg) and placebo administration. Before conditioning procedures began, they rated the two rooms to examine pre-existing preferences. One group (Paired, n = 19) always received d-amphetamine in their least preferred room and placebo in the other during conditioning sessions. Another group (Unpaired, n = 15) received d-amphetamine and placebo in both rooms. Subjective drug effects were monitored at repeated times. At a separate re-exposure test, preference ratings for the drug-associated room were increased among the Paired group only, and more subjects in the Paired than the Unpaired group switched their preference to their initially least preferred room. Also, ratings of d-amphetamine drug liking independently predicted room liking at test among the Paired group only. Further, Paired group subjects reported greater stimulation and drug craving after d-amphetamine on the second administration, relative to the first. This study supports preliminary findings that humans, like animals, develop a preference for a place associated with d-amphetamine that is related to its subjective effects. These findings also suggest that experiencing d-amphetamine in a consistent environment produces context-dependent changes in its subjective effects, including an enhanced rewarding efficacy and abuse potential. © 2011 The Authors, Addiction Biology © 2011 Society for the Study of Addiction.

  16. Combination of modafinil and d-Amphetamine for the treatment of cocaine dependence: A preliminary investigation

    Directory of Open Access Journals (Sweden)

    Joy M Schmitz

    2012-08-01

    Full Text Available Background: Two stimulant medications, modafinil and d-amphetamine, when tested individually, have shown safety and efficacy for treatment of cocaine addiction. We hypothesized that the combination of modafinil and d-amphetamine, at low doses, would show equivalent or greater benefit in reducing cocaine use compared to higher doses of each individual medication or placebo. Methods: Sixteen week, randomized, parallel-group design with four treatment arms comparing placebo to modafinil 400 mg; d-amphetamine 60 mg; modafinil 200 mg plus d-amphetamine 30 mg. Primary outcome variables, retention and cocaine use, were analyzed on the sample of 73 participants who received the first dose of the study medication. Results: Retention rates did not differ between groups and were generally low, with 40% remaining in treatment at week 12 and 20% at week 16. Participants receiving the combination of modafinil and d-amphetamine showed a trend of increased cocaine use over time with a corresponding low Bayesian probability of benefit (33%. Relatively better cocaine outcomes were observed in the placebo and d-amphetamine only groups. The study medications were generally well-tolerated with few adverse effects, yet rates of adherence were suboptimal (≤ 80%. Conclusion: Data from this preliminary investigation fail to provide evidential support for conducting a larger study of this dual-agonist medication combination for treatment of cocaine dependence.

  17. Effects of 7-day continuous D-amphetamine, methylphenidate, and cocaine treatment on choice between methamphetamine and food in male rhesus monkeys.

    Science.gov (United States)

    Schwienteck, Kathryn L; Banks, Matthew L

    2015-10-01

    Methamphetamine addiction is a significant public health problem for which no Food and Drug Administration-approved pharmacotherapies exist. Preclinical drug vs. food choice procedures have been predictive of clinical medication efficacy in the treatment of opioid and cocaine addiction. Whether preclinical choice procedures are predictive of candidate medication effects for other abused drugs, such as methamphetamine, remains unclear. The present study aim was to determine continuous 7-day treatment effects with the monoamine releaser d-amphetamine and the monoamine uptake inhibitor methylphenidate on methamphetamine vs. food choice. In addition, 7-day cocaine treatment effects were also examined. Behavior was maintained under a concurrent schedule of food delivery (1-g pellets, fixed-ratio 100 schedule) and methamphetamine injections (0-0.32mg/kg/injection, fixed-ratio 10 schedule) in male rhesus monkeys (n=4). Methamphetamine choice dose-effect functions were determined daily before and during 7-day periods of continuous intravenous treatment with d-amphetamine (0.01-0.1mg/kg/h), methylphenidate (0.032-0.32mg/kg/h), or cocaine (0.1-0.32mg/kg/h). During saline treatment, increasing methamphetamine doses resulted in a corresponding increase in methamphetamine vs. food choice. Continuous 7-day treatments with d-amphetamine, methylphenidate or cocaine did not significantly attenuate methamphetamine vs. food choice up to doses that decreased rates of operant responding. However, 0.1mg/kg/h d-amphetamine did eliminate methamphetamine choice in two monkeys. The present subchronic treatment results support the utility of preclinical methamphetamine choice to evaluate candidate medications for methamphetamine addiction. Furthermore, these results confirm and extend previous results demonstrating differential pharmacological mechanisms between cocaine choice and methamphetamine choice. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  18. Effects of 7-day continuous d-amphetamine, methylphenidate, and cocaine treatment on choice between methamphetamine and food in male rhesus monkeys*

    Science.gov (United States)

    Schwienteck, Kathryn L.; Banks, Matthew L.

    2015-01-01

    Background Methamphetamine addiction is a significant public health problem for which no Food and Drug Administration-approved pharmacotherapies exist. Preclinical drug vs. food choice procedures have been predictive of clinical medication efficacy in the treatment of opioid and cocaine addiction. Whether preclinical choice procedures are predictive of candidate medication effects for other abused drugs, such as methamphetamine, remains unclear. The present study aim was to determine continuous 7-day treatment effects with the monoamine releaser d-amphetamine and the monoamine uptake inhibitor methylphenidate on methamphetamine vs. food choice.In addition, 7-day cocaine treatment effects were also examined. Methods Behavior was maintained under a concurrent schedule of food delivery (1-g pellets, fixed-ratio 100 schedule) and methamphetamine injections (0-0.32 mg/kg/injection, fixed-ratio 10 schedule) in male rhesus monkeys (n=4). Methamphetamine choice dose-effect functions were determined daily before and during 7-day periods of continuous intravenous treatment with d-amphetamine (0.01-0.1 mg/kg/h), methylphenidate (0.032-0.32 mg/kg/h), or cocaine (0.1-0.32 mg/kg/h). Results During saline treatment, increasing methamphetamine doses resulted in a corresponding increase in methamphetamine vs. food choice. Continuous 7-day treatments with d-amphetamine, methylphenidate or cocaine did not significantly attenuate methamphetamine vs. food choice up to doses that decreased rates of operant responding. However, 0.1 mg/kg/h d-amphetamine did eliminate methamphetamine choice in two monkeys. Conclusions The present subchronic treatment resultssupport the utility of preclinical methamphetamine choice to evaluate candidate medications for methamphetamine addiction. Furthermore, these results confirm and extend previous results demonstrating differential pharmacological mechanisms between cocaine choice and methamphetamine choice. PMID:26361713

  19. Reinforcer magnitude affects delay discounting and influences effects of d-amphetamine in rats.

    Science.gov (United States)

    Krebs, Christopher A; Reilly, William J; Anderson, Karen G

    2016-09-01

    Impulsive choice in humans can be altered by changing reinforcer magnitude; however, this effect has not been found in rats. Current levels of impulsive choice can also influence effects of d-amphetamine. This study used a within-subject assessment to determine if impulsive choice is sensitive to changes in reinforcer magnitude, and whether effects of d-amphetamine are related to current levels of impulsive choice. A discounting procedure in which choice was for a smaller reinforcer available immediately or a larger reinforcer available after a delay that increased within session was used. Reinforcer magnitude was manipulated between conditions and impulsive choice was quantified using area under the curve (AUC). In the Smaller-Magnitude (SM) Condition, choice was between one food pellet and three food pellets. In the Larger-Magnitude (LM) Condition, choice was between two food pellets and six food pellets. Impulsive choice was greater in the SM Condition compared to the LM Condition. Further, effects of d-amphetamine (0.1-1.8mg/kg) were related to differences in impulsive choice. d-Amphetamine increased impulsive choice in the LM Condition, but had no effect on impulsive choice in the SM Condition. Overall, these results show that impulsive choice in rats is sensitive to changes in reinforcer magnitude, and that effects of d-amphetamine are influenced by current levels of impulsive choice. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. The effects of d-amphetamine on extrastriatal dopamine D{sub 2}/D{sub 3} receptors: a randomized, double-blind, placebo-controlled PET study with [{sup 11}C]FLB 457 in healthy subjects

    Energy Technology Data Exchange (ETDEWEB)

    Aalto, Sargo [University of Turku, Turku PET Centre, Turku (Finland); Aabo Akademi University, Department of Psychology, Turku (Finland); Hirvonen, Jussi; Kajander, Jaana; Naagren, Kjell; Rinne, Juha O. [University of Turku, Turku PET Centre, Turku (Finland); Kaasinen, Valtteri [University of Turku, Department of Neurology, P.O. Box 52, Turku (Finland); Hagelberg, Nora [University of Turku, Turku PET Centre, Turku (Finland); Turku University Central Hospital, Department of Anaesthesiology, Intensive Care, Emergency Care and Pain Medicine, Turku (Finland); Seppaelae, Timo [Drug Research Unit, National Public Health Institute, Helsinki (Finland); Scheinin, Harry [University of Turku, Turku PET Centre, Turku (Finland); University of Turku, Department of Pharmacology, Drug Development and Therapeutics, Turku (Finland); Hietala, Jarmo [University of Turku, Turku PET Centre, Turku (Finland); University of Turku, Department of Psychiatry, Turku (Finland)

    2009-03-15

    The dopamine D{sub 2}/D{sub 3} receptor ligand [{sup 11}C]FLB 457 and PET enable quantification of low-density extrastriatal D{sub 2}/D{sub 3} receptors, but it is uncertain whether [{sup 11}C]FLB 457 can be used for measuring extrastriatal dopamine release. We studied the effects of d-amphetamine (0.3 mg/kg i.v.) on extrastriatal [{sup 11}C]FLB 457 binding potential (BP{sub ND}) in a randomized, double-blind, placebo-controlled study including 24 healthy volunteers. The effects of d-amphetamine on [{sup 11}C]FLB 457 BP{sub ND} and distribution volume (V{sub T}) in the frontal cortex were not different from those of placebo. Small decreases in [{sup 11}C]FLB 457 BP{sub ND} were observed only in the posterior cingulate and hippocampus. The regional changes in [{sup 11}C]FLB 457 BP{sub ND} did not correlate with d-amphetamine-induced changes in subjective ratings of euphoria. This placebo-controlled study showed that d-amphetamine does not induce marked changes in measures of extrastriatal dopamine D{sub 2}/D{sub 3} receptor binding. Our results indicate that [{sup 11}C]FLB 457 PET is not a useful method for measuring extrastriatal dopamine release in humans. (orig.)

  1. Prepulse inhibition of the acoustic startle reflex in pigs and its disruption by d-amphetamine

    DEFF Research Database (Denmark)

    Lind, Nanna Marie; Arnfred, Sidse M; Hemmingsen, Ralf P

    2004-01-01

    for validation of a pig model of psychosis, we wished to verify the existence of PPI in landrace pigs and investigate the potential disruption of PPI by d-amphetamine (AMPH) in these animals. PPI of the acoustic startle reflex and its potential disruption by AMPH were investigated using three doses 0.5-1.5mg...... and, in spite of only the 0.5mg/kg dose proved statistically significant, the results indicate this to be dose-related. We have demonstrated the phenomenon of PPI of the startle reflex in landrace pigs and its disruption by d-amphetamine. Studies of sensorimotor gating defects could be a valuable...

  2. [Sustained-release Opioids: Morphine, Oxycodone and Tapentadol].

    Science.gov (United States)

    Takahashi, Yoshika; Iseki, Masako

    2015-11-01

    Opioid analgesics are widely used for managing moderate to severe pain. In cancer pain management sustained-release opioids are used for continuous pain as well as immediate-release opioids for breakthrough pain. Sustained-release drugs have the advantage of stabilizing the blood concentration, although it takes some time to exert their effects. In Japan, the currently available oral sustained-release opioids include six types of sustained-release morphine (three are once-a-day formulations, while the rest are twice-a-day), one type of oxycodone and tapentadol. In this article, we will discuss the pharmacokinetic properties of MS Contin, Morphes, Kadian, P guard and Pacif as sustained-release morphine, Oxycontin as sustained-release oxycodone and Tapenta as sustained-release tapentadol.

  3. Development of enteric coated sustained release minitablets containing mesalamine

    National Research Council Canada - National Science Library

    Souza, Dayse Fernanda de; Goebel, Karin; Andreazza, Itamar Francisco

    2013-01-01

    The aim of this study was to develop and evaluate a multiparticulate modified release system, composed of minitablets with a sustained release matrix system coated with a pH-dependent release polymer...

  4. Altered response evaluation: Monitoring of late responses after administration of D-amphetamine

    NARCIS (Netherlands)

    Bruijn, E.R.A. de; Hulstijn, W.; Verkes, R.J.; Ruigt, G.S.F.; Sabbe, B.G.C.

    2005-01-01

    Recently, D-amphetamine was shown to increase the error negativity, the so-called "response Ne/ERN," after incorrect choices of hand. We investigated whether this stimulation of action monitoring would also be present in the monitoring of late responses, reflected in the "late Ne/ERN." Twelve

  5. Effects of environmental enrichment on d-amphetamine self-administration following nicotine exposure.

    Science.gov (United States)

    Stairs, Dustin J; Ewin, Sarah E; Kangiser, Megan M; Pfaff, Markus N

    2017-10-01

    Adolescent nicotine exposure has been shown to lead to further psychostimulant use in adulthood. Previous preclinical research in rats has shown that environmental enrichment may protect against drug abuse vulnerability. The current study was designed to examine whether environmental enrichment can block the ability of adolescent nicotine exposure to increase d-amphetamine self-administration in adulthood. Male Sprague-Dawley rats were raised in either enriched conditions (ECs) or isolated conditions (ICs) and then injected with saline or nicotine (0.4 mg/kg, sc) for 7 days during adolescence. In adulthood rats were allowed to self-administer d-amphetamine under a fixed ratio (FR; 0, 0.006, 0.01, 0.02, 0.06, and 0.1 mg/kg/infusion) and progressive ratio (PR; 0, 0.006, 0.06, and 0.1 mg/kg/infusion) schedule of reinforcement. Nicotine-treated IC rats self-administered more d-amphetamine at 0.006, 0.01, and 0.02 mg/kg/infusion doses compared with their saline-treated IC counterparts regardless of the schedule maintaining behavior. This effect of nicotine was reversed in EC rats on a fixed ratio schedule. These findings indicate that environmental enrichment can limit the ability of adolescent nicotine exposure to increase vulnerability to other psychostimulant drugs, such as d-amphetamine. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  6. [Study on sustained release preparations of Epimedium component].

    Science.gov (United States)

    Yan, Hong-mei; Ding, Dong-mei; Zhang, Zhen-hai; Sun, E; Song, Jie; Jia, Xiao-bin

    2015-04-01

    The formulation for sustained release tablet of Epinedium component was selected and the evaluation equation of in vitro release was established. The liquidity of component was improved with the help of colloidal silica aided by spray drying, which would be the main drug in the sustained release tablets. Dissolution was selected as an evaluation index to investigate skeletal material type, fillers, impact porogen, lubricants and other materials on the quality of sustained release tablet. The sustained release tablets were prepared by dry compression. Formulation of sustained release preparations was main drug 35%, HPMC K(4M) 20% and HPMC K(15M) 10% as skeleton material, MCC 31% as filler, PEG6000 2% as porogen and magnesium stearate 2% as lubricant. The sustained release tablets released up to 80% in 8 h. The zero order equation, primary equation and Higuchi equation could simulate the release characteristics of sustained release tablets in vitro, the correlation coefficients r were larger than 0.96. The primary equation was most similar in vitro release characteristics and its correlation coefficient r was 0.9950. The preparation method is simple and the results of formulation selection are reliable. It can be used to guide the production of Epimedium component sustained release preparations.

  7. Effects of artemisinin sustained-release granules on mixed alga growth and microcystins production and release.

    Science.gov (United States)

    Ni, Lixiao; Li, Danye; Hu, Shuzhen; Wang, Peifang; Li, Shiyin; Li, Yiping; Li, Yong; Acharya, Kumud

    2015-12-01

    To safely and effectively apply artemisinin sustained-release granules to control and prevent algal water-blooms, the effects of artemisinin and its sustained-release granules on freshwater alga (Scenedesmus obliquus (S. obliquus) and Microcystis aeruginosa (M. aeruginosa)), as well as the production and release of microcystins (MCs) were studied. The results showed that artemisinin sustained-release granules inhibited the growth of M. aeruginosa (above 95% IR) and S. obliquus (about 90% IR), with M. aeruginosa more sensitive. The artemisinin sustained-release granules had a longer inhibition effect on growth of pure algae and algal coexistence than direct artemisinin dosing. The artemisinin sustained-release granules could decrease the production and release of algal toxins due to the continued stress of artemisinin released from artemisinin sustained-release granules. There was no increase in the total amount of MC-LR in the algal cell culture medium.

  8. Involvement of nucleus accumbens AMPA receptor trafficking in augmentation of D- amphetamine reward in food-restricted rats.

    Science.gov (United States)

    Peng, Xing-Xiang; Cabeza de Vaca, Soledad; Ziff, Edward B; Carr, Kenneth D

    2014-08-01

    Chronic food restriction (FR) increases behavioral responsiveness to drugs of abuse and associated environments. Pre- and postsynaptic neuroadaptations have been identified in the mesoaccumbens dopamine pathway of FR subjects but the mechanistic basis of increased drug reward magnitude remains unclear. Effects of FR on basal and D-amphetamine-induced trafficking of AMPA receptor subunits to the nucleus accumbens (NAc) postsynaptic density (PSD) were examined, and AMPA receptor involvement in augmentation of D-amphetamine reward was tested. FR and ad libitum fed (AL) rats were injected with D-amphetamine (2.5 mg/kg, i.p.) or vehicle. Brains were harvested and subcellular fractionation and Western analyses were used to assess AMPA receptor abundance in NAc homogenate and PSD fractions. A follow-up experiment used a curve-shift protocol of intracranial self-stimulation to assess the effect of 1-naphthylacetyl spermine (1-NASPM), a blocker of Ca(2+)-permeable AMPA receptors, on rewarding effects of D-amphetamine microinjected in NAc shell. FR increased GluA1 in the PSD, and D-amphetamine increased p-Ser845-GluA1, GluA1, GluA2, but not GluA3, with a greater effect in FR than AL rats. D-amphetamine lowered reward thresholds, with greater effects in FR than AL rats, and 1-NASPM selectively reversed the enhancing effect of FR. Results suggest that FR leads to increased synaptic incorporation of GluA1 homomers to potentiate rewarding effects of appetitive stimuli and, as a maladaptive byproduct, D-amphetamine. The D-amphetamine-induced increase in synaptic p-Ser845-GluA1, GluA1, and GluA2 may contribute to the rewarding effect of D-amphetamine, but may also be a mechanism of synaptic strengthening and behavior modification.

  9. Effects of 21-day d-amphetamine and risperidone treatment on cocaine vs food choice and extended-access cocaine intake in male rhesus monkeys.

    Science.gov (United States)

    Hutsell, Blake A; Negus, S Stevens; Banks, Matthew L

    2016-11-01

    Clinical trial data suggest amphetamine treatment is most efficacious in moderate to high frequency cocaine users. However, preclinical studies have examined amphetamine treatment effects under relatively limited cocaine access conditions with low to moderate cocaine intakes. This study determined d-amphetamine treatment effects on cocaine self-administration in rhesus monkeys under cocaine access conditions allowing for high daily cocaine intake. For comparison and as a negative control, treatment effects with the antipsychotic risperidone were also examined. Continuous 21-day treatments with ramping doses of d-amphetamine (days 1-7: 0.032mg/kg/h; days 8-21: 0.1mg/kg/h, i.v.) or risperidone (days 1-7: 0.001mg/kg/h; days 8-14: 0.0032mg/kg/h; days 15-21: 0.0056mg/kg/h, i.v.) were administered to rhesus monkeys (n=4) with daily access to two types of cocaine self-administration sessions: (1) a 2-h 'choice' session with concurrent availability of 1-g food pellets and intravenous cocaine injections (0-0.1mg/kg per injection) and (2) a 20-h 'extended-access' session with 0.1mg/kg per injection cocaine availability. Total daily cocaine intake increased >6-fold during extended cocaine access. d-Amphetamine significantly decreased total cocaine intake, but not cocaine vs food choice. In contrast, risperidone did not significantly alter either total cocaine intake or cocaine vs. food choice. These results confirm and extend previous results supporting treatment effectiveness for monoamine releasers, but not dopamine antagonists, to reduce cocaine self-administration. Moreover, these results suggest amphetamine treatment efficacy to decrease preclinical cocaine vs. food choice may depend upon cocaine access conditions. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  10. Personality and the acute subjective effects of d-amphetamine in humans

    OpenAIRE

    Kirkpatrick, Matthew G; Johanson, Chris-Ellyn; de Wit, Harriet

    2013-01-01

    There is evidence that subjective responses to psychoactive drugs are related to personality traits. Here, we extend previous findings by examining personality measures in relation to acute responses to d-amphetamine (AMPH) in a large sample of healthy volunteers. Healthy adults (n=286) completed the Multidimensional Personality Questionnaire Brief Form (MPQ-BF) and participated in four sessions during which they received oral AMPH (0, 5,10, 20 mg), under double-blind conditions. Subjective r...

  11. Behavioral effects of bidirectional modulation of brain monoamines by reserpine and d-amphetamine in zebrafish

    OpenAIRE

    Kyzar, Evan; Stewart, Adam Michael; Landsman, Samuel; Collins, Christopher; Gebhardt, Michael; Robinson, Kyle; Kalueff, Allan V.

    2013-01-01

    Brain monoamines play a key role in the regulation of behavior. Reserpine depletes monoamines, and causes depression and hypoactivity in humans and rodents. In contrast, d-amphetamine increases brain monoamines’ levels, and evokes hyperactivity and anxiety. However, the effects of these agents on behavior and in relation to monoamine levels remain poorly understood, necessitating further experimental studies to understand their psychotropic action. Zebrafish (Danio rerio) are rapidly emerging...

  12. D-Amphetamine remediates attentional performance in rats with dorsal prefrontal lesions.

    Science.gov (United States)

    Chudasama, Y; Nathwani, F; Robbins, T W

    2005-03-07

    Although amphetamine treatment has been shown to promote recovery of motor function in animals with cortical ablations, the potential therapeutic effect of amphetamine on processes other than motor control, such as attention and working memory, has been relatively unexplored. Accordingly, we investigated the beneficial effect of D-amphetamine treatment in animals with dorsal prefrontal cortex lesions (dPFC) compared with sham controls on a novel combined attention-memory task (CAM) that simultaneously measures attention to a visual stimulus and memory for that stimulus. The dPFC group was impaired in their ability to correctly detect the visual stimulus. Although this deficit occurred together with increased omissions and slow response latencies, these associated deficits largely recovered within the 10 post-operative baseline sessions revealing a selective attentional deficit in this group of animals. Nonetheless, the dPFC lesion did not substantially affect the working memory component of the task. The systemic administration of d-amphetamine served to ameliorate the attentional deficit in the dPFC group at the low dose only (0.2 mg/kg). By contrast, the dPFC group were less sensitive to the detrimental effects of the high dose (0.8 mg/kg) on any aspect of task performance. However, despite improving attention to the visual stimulus, D-amphetamine did not improve memory for that stimulus which instead appeared to deteriorate. The results provide apparently the first demonstration that low doses of D-amphetamine can ameliorate an attentional deficit in animals with selective dPFC lesions and may be a useful model of cognitive deficit in ADHD, schizophrenia or frontal brain injury.

  13. Design and development of sustained-release glyburide-loaded ...

    Indian Academy of Sciences (India)

    Home; Journals; Bulletin of Materials Science; Volume 40; Issue 2. Design and development of sustained-release ... Keywords. Silica nanoparticles; glyburide; sustained release; sol–gel method. ... Silica nanoparticles were synthesized by the sol–gel method using tetra-ethyl ortho-silane as a precursor. Glyburide was ...

  14. Effect of D-amphetamine on dopaminergic neurons of substantia nigra and expression of tyrosine hydroxylase in striatum and pre-frontal cortex of D-amphetamine treated Wistar rats

    Directory of Open Access Journals (Sweden)

    Sarun Koirala

    2014-10-01

    Full Text Available Dopaminergic neurons of the midbrain are the main source of dopamine in the mammalian central nervous system. Dopamine is a chemical messenger active in mesolimbic and mesocortical reward pathways. Dopamine is manufactured in nerve cell bodies in the ventral tegmental area (VTA and is released in the nucleus accumbens and the prefrontal cortex. The objective was to compare dopaminergic neurons of substantia nigra and level of tyrosine hydroxylase (TH in the striatum and pre-frontal cortex of D-amphetamine treated wistar mice. 15 Wistar rats were injected subcutaneously with amphetamine 10 mg/kg body weight till 7 days while the controls groups (15 wistar rats were injected with normal saline in the same dose. One way-ANOVA test and Post-hoc tests was applied and decreased level of tyrosine hydroxylase was present in striatum (65% and pre-frontal cortex (71%. The percentage of tyrosine hydroxylase in all these areas were highly significant (p<0.001. D-AMPH affects the neuronal cell morphology and decreases expression level of Tyrosine hydroxylase. Degeneration of dopaminergic neurons and damaged synaptic connection in substantia nigra were observed leading to a reduction of stratial dopamine levels.

  15. Preparation and Dissolution Characteristics of Sustained Release ...

    African Journals Online (AJOL)

    In the present study, the applicability of Eudragit to produce matrix tablet by a wet granulation technique was evaluated. The effect of various formulation variables on the release of drug from these tablets was examined. Release profiles of diltiazem hydrochloride were investigated using the rotating basket method ...

  16. Comparison of intranasal methamphetamine and d-amphetamine self-administration by humans

    Science.gov (United States)

    Kirkpatrick, Matthew G.; Gunderson, Erik W.; Johanson, Chris-Ellyn; Levin, Frances R.; Foltin, Richard W.; Hart, Carl L.

    2012-01-01

    Aims Anecdotally, methamphetamine is considered to have a greater abuse potential compared to d-amphetamine, but there are no studies directly comparing self-administration of these drugs. This study characterized and compared self-administration as well as the mood, performance, and physiological effects of intranasal methamphetamine- and d-amphetamine. Design A randomized, double-blind, placebo-controlled, cross-over study. Setting An outpatient research unit at the New York State Psychiatric Institute. Participants Male recreational methamphetamine users (n = 13). Measurements Five 2-day blocks of sessions were conducted. On the first day of each block, participants “sampled” a single methamphetamine or d-amphetamine dose (0, 12, 50 mg/70 kg) and a monetary reinforcer ($5 or $20). Amphetamines plasma levels, cardiovascular, mood, and psychomotor performance effects were assessed before drug administration and repeatedly thereafter. On the second day of each block, participants chose between the sampled reinforcers (drug or money). Findings There were no significant differences between the drugs on the majority of measures. Under the $5 condition, both amphetamines dose-dependently increased self-administration, whereas under the $20 condition, few drug options were selected. Overall, participants selected more drug choices under the $5 condition compared with the $20 condition (41% versus 17%). Both drugs increased cardiovascular activity and “positive” mood, although methamphetamine produced more prominent effects on some measures (e.g., heart rate and ratings of ‘high’). Conclusions These data are consistent with previous findings suggesting that the two amphetamines produce a similar dose-related profile of acute effects in humans, with methamphetamine producing greater effects on some mood and cardiovascular measures. The amphetamines were self-administered equally indicating their equivalence for abuse potential. PMID:22050030

  17. Multivariate analysis of subjective responses to d-amphetamine in healthy volunteers finds novel genetic pathway associations.

    Science.gov (United States)

    Yarosh, Haley L; Meda, Shashwath A; de Wit, Harriet; Hart, Amy B; Pearlson, Godfrey D

    2015-08-01

    Researchers studying behavioral and physiologic effects of d-amphetamine have explored individual response differences to the drug. Concurrently, genome-wide analyses have identified several single-nucleotide polymorphisms (SNPs) associated with these traits. Univariate methods can identify SNPs associated with behavioral and physiological traits, but multivariate analyses allow identification of clusters of related biologically relevant SNPs and behavioral components. The aim of the study was to identify clusters of related biologically relevant SNPs and behavioral components in the responses of healthy individuals to d-amphetamine using multivariate analysis. Individuals (N = 375) without substance abuse histories completed surveys and detailed cardiovascular monitoring during randomized, blinded sessions: d-amphetamine (10 and 20 mg) and placebo. We applied parallel independent component analysis (Para-ICA) to data previously analyzed with univariate approaches, revealing new associations between genes and behavioral responses to d-amphetamine. Three significantly associated (p amphetamine addiction appear to mediate common behavioral and cardiovascular responses to d-amphetamine.

  18. Preparation and Evaluation of Sustained Release Matrix Tablets of ...

    African Journals Online (AJOL)

    Erah

    Purpose: To prepare oral sustained release matrix tablets of a highly water soluble drug, tramadol hydrochloride, and to evaluate the effect of .... (IRAffinity-1, Shimadzu). Their spectra were obtained over the wave number range of ... square root kinetic model describes a time- dependent release process. The value of n.

  19. Role of d-amphetamine and d-methamphetamine as active metabolites of benzphetamine: Evidence from drug discrimination and pharmacokinetic studies in male rhesus monkeys.

    Science.gov (United States)

    Banks, Matthew L; Snyder, Rodney W; Fennell, Timothy R; Negus, S Stevens

    2017-05-01

    Benzphetamine is a Schedule III anorectic agent that is a prodrug for d-amphetamine and d-methamphetamine and may have utility as an "agonist" medication for cocaine use disorder treatment. This study evaluated the pharmacokinetic-pharmacodynamic profile of benzphetamine using a drug discrimination procedure in rhesus monkeys. The potency and time course of cocaine-like discriminative stimulus effects were compared for benzphetamine (10-18mg/kg, intramuscular (IM)) and d-amphetamine (0.032-0.32mg/kg, IM) in monkeys (n=3-4) trained to discriminate IM cocaine (0.32mg/kg) from saline in a two-key food-reinforced discrimination procedure. Parallel pharmacokinetic studies in the same monkeys determined plasma benzphetamine, d-methamphetamine and/or d-amphetamine levels for correlation with behavioral effects. d-Amphetamine produced dose-dependent, time-dependent, and full cocaine-like effects, i.e. ≥90% cocaine-appropriate responding, in all monkeys without altering response rates. The time course of d-amphetamine's cocaine-like discriminative stimulus effects correlated with plasma d-amphetamine levels. Benzphetamine was 180-fold less potent than d-amphetamine and produced full cocaine-like effects in only 2 of 4 monkeys while significantly decreasing response rates. Benzphetamine administration increased plasma d-methamphetamine (peak at 100min) and d-amphetamine (peak at 24h) levels, but the time course of behavioral effects did not correlate with increased levels of benzphetamine, d-methamphetamine or d-amphetamine. These results suggest that benzphetamine yields d-amphetamine and d-methamphetamine as active metabolites in rhesus monkeys, but generation of these metabolites is not sufficient to account for benzphetamine behavioral effects. The incomplete cocaine substitution profile and protracted d-amphetamine plasma levels suggest that benzphetamine may still warrant further evaluation as a candidate pharmacotherapy for cocaine use disorder treatment. Copyright

  20. DEVELOPMENT OF SUSTAINED RELEASE TABLETS CONTAINING SOLID DISPERSIONS OF BACLOFEN

    Directory of Open Access Journals (Sweden)

    K. H. Janardhana

    2015-07-01

    Full Text Available Sustained release tablets containing solid dispersions granules of a poorly water soluble drug were prepared to investigate the controlled release of the drug. Baclofen was chosen because of its poor water solubility and short elimination half-life. Poloxamer 188 and PEG 6000 were used as solid dispersion carrier. Free flowing solid dispersion granules were prepared by adsorbing the melt of the drug and carriers onto the surface of an adsorbent, Carbopol 934P followed by direct compression with HPMC K4M and HPMC K100 to obtain an solid dispersion loaded sustained release tablets. FTIR studies confirmed that the compatibility of drug and carriers. Differential scanning calorimetry (DSC and X-ray diffraction (XRD revealed partially amorphous structures of the drug in solid dispersion granules. The solid dispersion granules dissolved completely within 30 min, which was much faster than that of pure drug baclofen. The sustained release of baclofen from the solid dispersion containing tablet was achieved for 2 h in gastric fluid (pH 1.2 and for up to 10 h in intestinal fluid (pH 6.8. A combination of solid dispersion techniques using adsorption and sustained release concepts is a promising approach to control the release rate of poorly water-soluble drugs.

  1. Naproxen release from sustained release matrix system and effect of cellulose derivatives.

    Science.gov (United States)

    Sarfraz, Muhammad Khan; Rehman, Nisar Ur; Mohsin, Sabeeh

    2006-07-01

    The present study was conducted to investigate the low viscosity grades of hydroxypropylmethyl cellulose (HPMC) and ethyl cellulose (EC) in sustaining the release of water insoluble drug, naproxen from the matrix tablets. Both HPMC and EC were incorporated in the matrix system separately or in combinations by wet granulation technique. In vitro dissolution studies indicated that EC significantly reduced the rate of drug release compared to HPMC in 12 hour testing time. But, no significant difference was observed in the release profiles of matrix tablets made by higher percentages of EC. The tablets prepared with various combinations of HPMC and EC also failed to produce produce the desired release profiles. However, comparatively linear and desirable sustained release was obtained from EC-based matrix tablets prepared by slightly modifying the granulation method. Moreover, two different compression forces used in tableting had no remarkable effect on the release profile of naproxen.

  2. Molecularly imprinted polymer nanocarriers for sustained release of erythromycin.

    Science.gov (United States)

    Kempe, Henrik; Parareda Pujolràs, Anna; Kempe, Maria

    2015-02-01

    To develop and evaluate molecularly imprinted nanocarriers for sustained release of erythromycin in physiological buffer media. Erythromycin-imprinted poly(methacrylic acid-co-trimethylolpropane trimethacrylate) nanocarriers and corresponding control nanocarriers were prepared by free-radical precipitation polymerization. The nanocarriers were characterized by transmission electron microscopy, dynamic light scattering, and nitrogen sorption analysis. Binding studies were carried out with erythromycin and five structurally unrelated drugs. Molecular descriptors of the drugs were computed and correlated to measured binding data by multivariate data analysis. Loading with erythromycin and in vitro release studies were carried out in physiological buffer media. Kinetic models were fitted to drug release data. The template affected the size and morphology of the nanocarriers. Binding isotherms showed that erythromycin-imprinted nanocarriers had a higher erythromycin binding capacity than corresponding control nanocarriers. Multivariate data analysis, correlating binding to molecular descriptors of the drugs, indicated a molecular imprinting effect. Erythromycin loading capacity was 76 mg/g with a loading efficiency of 87%. Release studies in physiological buffer showed an initial burst release of a quarter of loaded erythromycin during the first day and an 82% release after a week. The release was best described by the Korsmeyer-Peppas model. Sustained release of erythromycin in physiological buffer was demonstrated.

  3. The d-amphetamine-treated Göttingen miniature pig: an animal model for assessing behavioral effects of antipsychotics

    NARCIS (Netherlands)

    Staay, van der F.J.; Pouzet, B.; Mahieu, M.; Nordquist, R.E.; Schuurman, T.

    2009-01-01

    Rationale Rodents are usually used to assess the ability of antipsychotic drugs to antagonize hyperlocomotion induced by dopamine agonists, such as the psychostimulant d-amphetamine. However, the substantial differences between rodents and humans may hinder extrapolation of experimental results to

  4. Sustained release from a metal - Analgesics entrapped within biocidal silver.

    Science.gov (United States)

    Menagen, Barak; Pedahzur, Rami; Avnir, David

    2017-06-23

    Matrices for sustained release of drugs have been based on polymers, biomaterials and oxides. The use of the major family of metals as matrices for sustained release is, to the best of our knowledge, unknown. In this context we describe a new family of bio-composites for sustained release of drugs, namely analgesic drugs entrapped within metallic silver. Synthetic methodologies were developed for the preparation of ibuprofen@Ag, naproxen@Ag, tramadol@Ag and bupivacaine@Ag composites. Detailed kinetic analysis of the release of the drugs from within the metal, is provided, demonstrating that metals can indeed serve as reservoirs for drug release. The metal in our case acts not only as a drug releasing source, but also as an antibacterial agent and this property of the composites was studied. Unexpectedly, it was found that the entrapment of the analgesics within silver, dramatically enhances the growth inhibition activity of wild type Pseudomonas aeruginosa, exceeding by far the inhibition activity of the separate components. A mechanism for this interesting observation is provided. The strong antimicrobial activity combined with the analgesic activity open the road for future applications of these materials as dual-purpose components in wound treatment.

  5. Formulation of Sustained-Release Matrix Tablets Using Cross ...

    African Journals Online (AJOL)

    HP

    2012-02-23

    Feb 23, 2012 ... appears simple, but in reality, the release pattern is a complex phenomenon. At the molecular level, it ... The drug is thus a suitable model candidate for sustained drug delivery [12]. The objective of the .... anomalous transport (non-Fickian) refers to a combination of both diffusion and erosion controlled-drug ...

  6. Formulation of Sustained-Release Matrix Tablets Using Cross ...

    African Journals Online (AJOL)

    Erah

    characterized by scanning electron microscopy (SEM), Fourier transform infra-red spectroscopy (FTIR) and differential scanning calorimetry (DSC). Results: Tablets with MK showed higher mean ..... Park CR, Munday DL. Evaluation of selected polysaccharide excipients in buccoadhesive tablets for sustained release of ...

  7. Lyophilized Oral Sustained Release Polymeric Nanoparticles of Nateglinide

    OpenAIRE

    Kaleemuddin, Mohammad; Srinivas, Prathima

    2012-01-01

    The objective of this study is to formulate lyophilized oral sustained release polymeric nanoparticles of nateglinide in order to decrease dosing frequency, minimize side effects, and increase bioavailability. Nateglinide-loaded poly Ɛ-caprolactone nanoparticles were prepared by emulsion solvent evaporation with ultrasonication technique and subjected to various studies for characterization including scanning electron microscopy (SEM), Fourier transform infrared spectroscopy, photon correlati...

  8. daily, sustained-release theophylline on sleep in nocturnal asthmatics

    African Journals Online (AJOL)

    To examine the effects of once-daily, sustained- release theophylline on sleep patterns in nocturnal asthmatics. Design. Double-blind, randomised, cross-over, placebo- controlled trial ... 22-day trial, 3 patients having withdrawn due to adverse events. During the initial 7 days of the stUdy, serum was obtained at 07hOO and ...

  9. Development of Sustained-Release Microbeads of Nifedipine and In ...

    African Journals Online (AJOL)

    Purpose: To formulate and evaluate sustained-release microbeads of nifedipine for prolonged delivery. Methods: Nifedipine microbeads were prepared using sodium alginate and pectin in different ratios by ionic-gelation method. The microbeads were evaluated for surface morphology and shape by scanning electron ...

  10. daily, sustained-release theophylline on sleep in nocturnal asthmatics

    African Journals Online (AJOL)

    during the early hours of the morning and nocturnal asthma attacks are therefore not always prevented.2 However, improved control of nocturnal asthma has been reported with the use of once-daily, sustained-release, evening- administered theophylline.1. The influence of theophylline on sleep is not clear and.

  11. Formulation of Sustained-Release Matrix Tablets Using Cross ...

    African Journals Online (AJOL)

    SEM images of the tablets before and after dissolution showed some morphological changes on the tablet surface while FTIR and DSC thermogram studies confirmed ... Conclusion: The results of the study demonstrate that modified karaya gum is a potential matrix material for formulating suitable sustained-release matrix ...

  12. [Preparation and release behaviour of mesoporous silica/ethylcellulose sustained-release mini-matrix].

    Science.gov (United States)

    Wu, Qiao-li; Quan, Gui-lan; Hong, Yu; Wu, Lin-na; Zeng, You-mei; Li, Ge; Pan, Xin; Wu, Chuan-bin

    2015-04-01

    Hot-melt extrusion was applied to prepare mesoporous silica/ethylcellulose mini-matrix for sustained release, and fenofibrate was used as a model drug, ethylcellulose and xanthan gum were chosen as sustained-release agent and releasing moderator, respectively. This novel matrix obtained the controlled release ability by combining mesoporous silica drug delivery system and hot-melt extrusion technology. And mesoporous silica particle (SBA-15) was chosen as drug carrier to increase the dissolution rate of fenofibrate in this martix. Scanning electron microscope, transmission electron microscope, small angle X-ray powder diffraction and N2 adsorption-desorption were introduced to determine the particle morphology, particle size and pore structure of the synthesized SBA-15. The results showed that SBA-15 had a very high Brunauer-Emmett-Teller specific surface area, a narrow pore size distribution, large pore volume and a ordered two-dimensional hexagonal structure of p6mm symmetry. Differential scanning calorimetry and X-ray powder diffraction results demonstrated that fenofibrate dispersed in an amorphous state inside the pores of the mesoporous silica which contributed to the improvement in the dissolution rate. The drug release of mini-matrices was influenced by ethylcellulose viscosity grades and xanthan gum concentration, which increased with the increasing of xanthan gum concentration and decreasing of ethylcellulose viscosity. Mini-matrix containing 22% xanthan gum exhibited a good sustained release performance, and the drug release behavior followed the first-order kinetics.

  13. Statistical Optimization of Sustained Release Venlafaxine HCI Wax Matrix Tablet.

    Science.gov (United States)

    Bhalekar, M R; Madgulkar, A R; Sheladiya, D D; Kshirsagar, S J; Wable, N D; Desale, S S

    2008-01-01

    The purpose of this research was to prepare a sustained release drug delivery system of venlafaxine hydrochloride by using a wax matrix system. The effects of bees wax and carnauba wax on drug release profile was investigated. A 3(2) full factorial design was applied to systemically optimize the drug release profile. Amounts of carnauba wax (X(1)) and bees wax (X(2)) were selected as independent variables and release after 12 h and time required for 50% (t(50)) drug release were selected as dependent variables. A mathematical model was generated for each response parameter. Both waxes retarded release after 12 h and increases the t(50) but bees wax showed significant influence. The drug release pattern for all the formulation combinations was found to be approaching Peppas kinetic model. Suitable combination of two waxes provided fairly good regulated release profile. The response surfaces and contour plots for each response parameter are presented for further interpretation of the results. The optimum formulations were chosen and their predicted results found to be in close agreement with experimental findings.

  14. Sustained tobramycin release from polyphosphate double network hydrogels.

    Science.gov (United States)

    Lane, Dwight D; Fessler, Amber K; Goo, Seungah; Williams, Dustin L; Stewart, Russell J

    2017-03-01

    Sustained local delivery of antibiotics from a drug reservoir to treat or prevent bacterial infections can avoid many of the drawbacks of systemic administration of antibiotics. Prolonged local release of high concentrations of antibiotics may also be more effective at treating bacteria in established biofilm populations that are resistant to systemic antibiotics. A double network hydrogel comprising an organic polyphosphate pre-polymer network polymerized within a polyacrylamide network de-swelled to about 50% of its initial volume when the polyphosphate network was crosslinked with polycationic tobramycin, an aminoglycoside antibiotic. The antibiotic-loaded hydrogels contained approximately 200mg/ml of tobramycin. The hydrogels continuously released daily amounts of tobramycin above the Pseudomonas aeruginosa minimal bactericidal concentration for greater than 50days, over the pH range 6.0-8.0, and completely eradicated established P. aeruginosa biofilms within 72h in a flow cell bioreactor. The presence of physiological concentrations of Mg2+ and Ca2+ ions doubled the cumulative release over 60days. The polyphosphate hydrogels show promise as materials for sustained localized tobramycin delivery to prevent post-operative P. aeruginosa infections including infections established in biofilms. Polyphosphate hydrogels were loaded with high concentrations of tobramycin. The hydrogels provided sustained release of bactericidal concentrations of tobramycin for 50days, and were capable of completely eradicating P. aeruginosa in established biofilms. The hydrogels have potential for localized prevention or treatment of P. aeruginosa infections. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  15. Lyophilized oral sustained release polymeric nanoparticles of nateglinide.

    Science.gov (United States)

    Kaleemuddin, Mohammad; Srinivas, Prathima

    2013-03-01

    The objective of this study is to formulate lyophilized oral sustained release polymeric nanoparticles of nateglinide in order to decrease dosing frequency, minimize side effects, and increase bioavailability. Nateglinide-loaded poly Ɛ-caprolactone nanoparticles were prepared by emulsion solvent evaporation with ultrasonication technique and subjected to various studies for characterization including scanning electron microscopy (SEM), Fourier transform infrared spectroscopy, photon correlation spectroscopy and evaluated for in vitro drug release and pharmacodynamic studies. The influence of increase in polymer concentration, ultrasonication time, and solvent evaporation rate on nanoparticle properties was investigated. The formulations were optimized based on the above characterization, and the formulation using 5% polymer, 3-min sonication time, and rota-evaporated was found to have the best drug entrapment efficiency of 64.09±4.27% and size of 310.40±11.42 nm. Based on SEM, nanoparticles were found to be spherical with a smooth surface. In vitro drug release data showed that nanoparticles sustained the nateglinide release for over 12 h compared to conventional tablets (Glinate 60 mg), and drug release was found to follow Fickian mechanism. In vivo studies showed that nanoparticles prolonged the antidiabetic activity of nateglinide in rats significantly (p≤0.05) compared to the conventional tablets (Glinate 60 mg) over a period of 12 h. Accelerated stability data indicated that there was minimal to no change in drug entrapment efficiency.

  16. Personality and the acute subjective effects of d-amphetamine in humans.

    Science.gov (United States)

    Kirkpatrick, Matthew G; Johanson, Chris-Ellyn; de Wit, Harriet

    2013-03-01

    There is evidence that subjective responses to psychoactive drugs are related to personality traits. Here, we extend previous findings by examining personality measures in relation to acute responses to d-amphetamine (AMPH) in a large sample of healthy volunteers. Healthy adults (n=286) completed the Multidimensional Personality Questionnaire Brief Form (MPQ-BF) and participated in four sessions during which they received oral AMPH (0, 5, 10, 20 mg), under double-blind conditions. Subjective responses to the drug were measured using the Profile of Mood States, Addiction Research Center Inventory, and Drug Effects Questionnaire. Drug responses were reduced via principal components analysis to three higher-order factors ('Euphoria', 'Arousal', 'Dysphoria'). Participants were rank ordered on selected MPQ-BF scales; the top and bottom third on each trait were compared on the drug response factors. High trait physical fearlessness was significantly associated with greater amphetamine-related Arousal, and high trait reward sensitivity was significantly associated with greater Euphoria. In addition, high trait impulsivity was significantly associated with greater Arousal and Euphoria. These results provide further evidence that individual differences in the subjective effects of AMPH are partially explained by differences in personality, and are consistent with the idea that both personality and responses to stimulants depend upon shared neurochemical systems.

  17. Sustained release of fungicide metalaxyl by mesoporous silica nanospheres

    Energy Technology Data Exchange (ETDEWEB)

    Wanyika, Harrison, E-mail: hwanyika@gmail.com [Jomo Kenyatta University of Agriculture and Technology, Department of Chemistry (Kenya)

    2013-08-15

    The use of nanomaterials for the controlled delivery of pesticides is nascent technology that has the potential to increase the efficiency of food production and decrease pollution. In this work, the prospect of mesoporous silica nanoparticles (MSN) for storage and controlled release of metalaxyl fungicide has been investigated. Mesoporous silica nanospheres with average particle diameters of 162 nm and average pore sizes of 3.2 nm were prepared by a sol-gel process. Metalaxyl molecules were loaded into MSN pores from an aqueous solution by a rotary evaporation method. The loaded amount of metalaxyl as evaluated by thermogravimetric analysis was about 14 wt%. Release of the fungicide entrapped in the MSN matrix revealed sustained release behavior. About 76 % of the free metalaxyl was released in soil within a period of 30 days while only 11.5 and 47 % of the metalaxyl contained in the MSN carrier was released in soil and water, respectively, within the same period. The study showed that MSN can be used to successfully store metalaxyl molecules in its mesoporous framework and significantly delay their release in soil.

  18. Comparison of the conditioned reinforcing properties of a safety signal and appetitive stimulus: effects of d-amphetamine and anxiolytics.

    Science.gov (United States)

    Fernando, A B P; Urcelay, G P; Mar, A C; Dickinson, A; Robbins, T W

    2013-05-01

    Safety signals providing relief are hypothesised to possess conditioned reinforcing properties, supporting the acquisition of a new response (AnR) as seen with appetitive stimuli. Such responding should also be sensitive to the rate-increasing effects of d-amphetamine and to the anxiolytics 8-OH-DPAT and diazepam. This study tests whether safety signals have conditioned reinforcing properties similar to those of stimuli-predicting reward. Rats received Pavlovian conditioning with either appetitive stimuli (CS+) or safety signals (conditioned inhibitors, CIs) plus truly random control (TRC) stimuli. The appetitive group received a CS + paired with a sucrose pellet and the safety signal group, a stimulus paired with shock omission. Stimuli were tested using an AnR procedure and following systemic d-amphetamine, the 5HT-1A agonist 8-OH-DPAT and the benzodiazepine diazepam in a counterbalanced design. Effective conditioning selectively reduced contextual freezing during CI presentation in the safety signal group and increased food magazine responses (with respect to context and TRC) during CS + presentation in the appetitive group. The appetitive stimulus strongly supported AnR but the safety signal did not. Systemic d-amphetamine significantly potentiated lever pressing in the appetitive group but for the safety signal group, it either reduced it or had no effect, dependent on food deprivation state. 8-OH-DPAT and diazepam had no effect on responding in either group. The safety signal did not support AnR and, therefore, did not exhibit conditioned reinforcing properties. Furthermore, d-amphetamine decreased responding when the safety signal was presented as a consequence, whilst increasing responding with appetitive-conditioned reinforcement. These results are discussed in terms of implications for opponent motivational theory.

  19. Sustained release nitric oxide from long-lived circulating nanoparticles.

    Science.gov (United States)

    Cabrales, Pedro; Han, George; Roche, Camille; Nacharaju, Parimala; Friedman, Adam J; Friedman, Joel M

    2010-08-15

    The current limitations of nitric oxide (NO) delivery systems have stimulated an extraordinary interest in the development of compounds that generate NO in a controlled and sustained manner with a heavy emphasis on the treatment of cardiovascular disease states. This work describes the positive physiological response to the infusion of NO-releasing nanoparticles prepared using a new platform based on hydrogel/glass hybrid nanoparticles. When exposed to moisture, these nanoparticles slowly release therapeutic levels of NO, previously generated through thermal reduction of nitrite to NO trapped within the dry particles. The controlled and sustained release of NO observed from these nanoparticles (NO-np) is regulated by its hydration over extended periods of time. In a dose-dependent manner, circulating NO-np both decreased mean arterial blood pressure and increased exhaled concentrations of NO over a period of several hours. Circulating NO-np induced vasodilatation and increased microvascular perfusion during their several hour circulation lifetime. Control nanoparticles (control-np; without nitrite) did not induce changes in arterial pressure, although a decrease in the number of capillaries perfused and an increase in leukocyte rolling and immobilization in the microcirculation were observed. The NO released by the NO-np prevents the inflammatory response observed after infusion of control-np. These data suggest that NO release from NO-np is advantageous relative to other NO-releasing compounds, because it does not depend on chemical decomposition or enzymatic catalysis; it is only determined by the rate of hydration. Based on the observed physiological properties, NO-np has clear potential as a therapeutic agent and as a research tool to increase our understanding of NO signaling mechanisms within the vasculature. Copyright (c) 2010 Elsevier Inc. All rights reserved.

  20. Adolescent d-amphetamine treatment in a rodent model of attention deficit/hyperactivity disorder: impact on cocaine abuse vulnerability in adulthood.

    Science.gov (United States)

    Jordan, Chloe J; Lemay, Carley; Dwoskin, Linda P; Kantak, Kathleen M

    2016-12-01

    Stimulant medications for attention-deficit/hyperactivity disorder (ADHD) in adolescents remain controversial with respect to later development of cocaine abuse. Past research demonstrated that adolescent methylphenidate treatment increased several aspects of cocaine self-administration during adulthood using the spontaneously hypertensive rat (SHR) model of ADHD. Presently, we determined effects of the alternate stimulant medication, d-amphetamine, on cocaine self-administration. We tested the hypothesis that adolescent d-amphetamine would not increase cocaine self-administration in adult SHR, given that d-amphetamine has a different mechanism of action than methylphenidate. A pharmacologically relevant dose of d-amphetamine (0.5 mg/kg) or vehicle was administered throughout adolescence to SHR and two control strains, Wistar-Kyoto (WKY) and Wistar (WIS). Three aspects of cocaine abuse vulnerability were assessed in adulthood after discontinuing adolescent treatments: acquisition rate and dose-related responding under fixed (FR) and progressive (PR) ratio schedules. Adult SHR acquired cocaine self-administration faster and self-administered more cocaine across multiple doses compared to WKY and WIS under FR and PR schedules, indicating that SHR is a reliable animal model of comorbid ADHD and cocaine abuse. Relative to vehicle, SHR and WIS with adolescent d-amphetamine treatment self-administered less cocaine upon reaching acquisition criteria, and WIS additionally acquired cocaine self-administration more slowly and had downward shifts in FR and PR cocaine dose-response curves. WKY with adolescent d-amphetamine treatment acquired cocaine self-administration more quickly relative to vehicle. In contrast to methylphenidate, adolescent d-amphetamine did not augment cocaine self-administration in SHR. Adolescent d-amphetamine treatment actually protected against cocaine abuse vulnerability in adult SHR and WIS.

  1. Autonomic, neuroendocrine, and immunological effects of ayahuasca: a comparative study with d-amphetamine.

    Science.gov (United States)

    Dos Santos, Rafael G; Valle, Marta; Bouso, José Carlos; Nomdedéu, Josep F; Rodríguez-Espinosa, José; McIlhenny, Ethan H; Barker, Steven A; Barbanoj, Manel J; Riba, Jordi

    2011-12-01

    Ayahuasca is an Amazonian psychotropic plant tea combining the 5-HT2A agonist N,N-dimethyltryptamine (DMT) and monoamine oxidase-inhibiting β-carboline alkaloids that render DMT orally active. The tea, obtained from Banisteriopsis caapi and Psychotria viridis, has traditionally been used for religious, ritual, and medicinal purposes by the indigenous peoples of the region. More recently, the syncretistic religious use of ayahuasca has expanded to the United States and Europe. Here we conducted a double-blind randomized crossover clinical trial to investigate the physiological impact of ayahuasca in terms of autonomic, neuroendocrine, and immunomodulatory effects. An oral dose of encapsulated freeze-dried ayahuasca (1.0 mg DMT/kg body weight) was compared versus a placebo and versus a positive control (20 mg d-amphetamine) in a group of 10 healthy volunteers. Ayahuasca led to measurable DMT plasma levels and distinct subjective and neurophysiological effects that were absent after amphetamine. Both drugs increased pupillary diameter, with ayahuasca showing milder effects. Prolactin levels were significantly increased by ayahuasca but not by amphetamine, and cortisol was increased by both, with ayahuasca leading to the higher peak values. Ayahuasca and amphetamine induced similar time-dependent modifications in lymphocyte subpopulations. Percent CD4 and CD3 were decreased, whereas natural killer cells were increased. Maximum changes occurred around 2 hours, returning to baseline levels at 24 hours. In conclusion, ayahuasca displayed moderate sympathomimetic effects, significant neuroendocrine stimulation, and a time-dependent modulatory effect on cell-mediated immunity. Future studies on the health impact of long-term ayahuasca consumption should consider the assessment of immunological status in regular users.

  2. Controlled Release System for Localized and Sustained Drug Delivery Applications

    Science.gov (United States)

    Rodriguez, Lidia Betsabe

    Current controlled release formulations has many drawbacks such as excess of initial burst release, low drug efficiency, non-degradability of the system and low reproducibility. The present project aims to offer an alternative by developing a technique to prepare uniform, biodegradable particles ( ˜19 mum ) that can sustainably release a drug for a specific period of time. Chitosan is a natural polysaccharide that has many characteristics to be used for biomedical applications. In the last two decades, there have been a considerable number of studies affirming that chitosan could be used for pharmaceutical applications. However, chitosan suffers from inherent weaknesses such as low mechanical stability and dissolution of the system in acidic media. In the present study, chitosan microparticles were prepared by emulsification process. The model drug chosen was acetylsalicylic acid as it is a small and challenging molecule. The maximum loading capacity obtained for the microparticles was approximately 96%. The parameters for the preparation of uniform particles with a narrow size distribution were identified in a triangular phase diagram. Moreover, chitosan particles were successfully coated with thin layers of poly lactic-coglycolic acid (PLGA) and poly lactic acid (PLA). The performance of different layerswas tested for in vitro drug release and degradation studies. Additionally, the degradability of the system was evaluated by measuring the weight loss of the system when exposed to enzyme and without enzyme. Scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), atomic force microscopy (AFM) and inductively coupled plasma optical emission spectrometry (ICP-OES) were used to characterize the controlled release system. Additionally, the in vitro drug release was monitored by ultraviolet-visible spectrophotometry (UV-Vis) and liquid chromatography mass spectrometry (LC-MS). The results obtained from this project showed that it is

  3. Minocycline inhibits D-amphetamine-elicited action potential bursts in a central snail neuron.

    Science.gov (United States)

    Chen, Y-H; Lin, P-L; Wong, R-W; Wu, Y-T; Hsu, H-Y; Tsai, M-C; Lin, M-J; Hsu, Y-C; Lin, C-H

    2012-10-25

    Minocycline is a second-generation tetracycline that has been reported to have powerful neuroprotective properties. In our previous studies, we found that d-amphetamine (AMPH) elicited action potential bursts in an identifiable RP4 neuron of the African snail, Achatina fulica Ferussac. This study sought to determine the effects of minocycline on the AMPH-elicited action potential pattern changes in the central snail neuron, using the two-electrode voltage clamping method. Extracellular application of AMPH at 300 μM elicited action potential bursts in the RP4 neuron. Minocycline dose-dependently (300-900 μM) inhibited the action potential bursts elicited by AMPH. The inhibitory effects of minocycline on AMPH-elicited action potential bursts were restored by forskolin (50 μM), an adenylate cyclase activator, and by dibutyryl cAMP (N(6),2'-O-Dibutyryladenosine 3',5'-cyclic monophosphate; 1mM), a membrane-permeable cAMP analog. Co-administration of forskolin (50 μM) plus tetraethylammonium chloride (TEA; 5mM) or co-administration of TEA (5mM) plus dibutyryl cAMP (1mM) also elicited action potential bursts, which were prevented and inhibited by minocycline. In addition, minocycline prevented and inhibited forskolin (100 μM)-elicited action potential bursts. Notably, TEA (50mM)-elicited action potential bursts in the RP4 neuron were not affected by minocycline. Minocycline did not affect steady-state outward currents of the RP4 neuron. However, minocycline did decrease the AMPH-elicited steady-state current changes. Similarly, minocycline decreased the effects of forskolin-elicited steady-state current changes. Pretreatment with H89 (N-[2-(p-Bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide dihydrochloride; 10 μM), a protein kinase A inhibitor, inhibited AMPH-elicited action potential bursts and decreased AMPH-elicited steady-state current changes. These results suggest that the cAMP-protein kinase A signaling pathway and the steady-state current are involved in

  4. The effects of d-govadine on conditioned place preference with d-amphetamine or food reward.

    Science.gov (United States)

    Nesbit, Maya O; Dias, Carine; Phillips, Anthony G

    2017-03-15

    Tetrahydroprotoberberines (THPB) have a high affinity for dopamine (DA) D1 and D2 receptors and may provide a novel treatment for drug addiction. We assessed the effects of the THPB d-govadine on the acquisition, expression, extinction and reinstatement of d-amphetamine-(1.5mg/kg, i.p.) induced conditioned place preference (CPP). Furthermore, the effects of d-govadine on conditioned association between contextual stimuli and a natural reward were examined using food-induced CPP. In separate experiments, rats received d-govadine (0, 0.5 or 1.0mg/kg, i.p.) before a) each d-amphetamine injection during conditioning, b) expression of amphetamine-induced CPP, c) each extinction session, d) amphetamine-induced reinstatement of CPP, or e) placement into a compartment containing food during conditioning. Although d-govadine had no effect on acquisition of amphetamine CPP, treatment with d-govadine during acquisition dose-dependently extinguished a preference for the amphetamine-associated context more quickly than vehicle treatment. Moreover, d-govadine treatment facilitated the extinction of amphetamine CPP when given repeatedly throughout the extinction phase. Although the expression of amphetamine CPP was not affected by d-govadine administered prior to the expression test, amphetamine-induced reinstatement of CPP following an extinction period was blocked by d-govadine (1.0mg/kg). The intermediate dose of d-govadine blocked the acquisition of food CPP, whereas the high dose facilitated extinction of this preference as compared to vehicle-treated animals. Therefore, d-govadine attenuates the maintenance of conditioned associations between contextual stimuli and amphetamine or food reward, as well as amphetamine-induced reinstatement of drug seeking behaviour. As such, d-govadine may be a candidate for further development as a pharmacological treatment of psychostimulant drug dependence. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Naltrexone sustained-release/bupropion sustained-release for the management of obesity: review of the data to date

    Science.gov (United States)

    Caixàs, Assumpta; Albert, Lara; Capel, Ismael; Rigla, Mercedes

    2014-01-01

    Obesity is an emerging disease worldwide. Changes in living habits, especially with increased consumption of high-calorie foods and decreased levels of physical activity, lead to an energy imbalance that brings weight gain. Overweight and obesity are major risk factors for several chronic diseases (including cardiovascular diseases, diabetes, and cancer), reduce quality of life, and are associated with higher mortality. For all these reasons, it is of the utmost importance that the trend be reversed and obese people enabled to lose weight. It is known that eating a healthy diet and exercising regularly can help prevent obesity, but data show that in many cases these steps are not enough. This is the reason why, over the last few decades, several antiobesity drugs have been developed. However, the disappointing results demonstrated for the vast majority of them have not discouraged the pharmaceutical industry from continuing to look for an effective drug or combination of drugs. The systematic review presented here focuses on naltrexone sustained-release/bupropion sustained-release combination (Contrave®). We conclude from the current published reports that its effectiveness in the treatment of obesity can be estimated as a placebo-subtracted weight loss of around 4.5%. This weight reduction is moderate but similar to other antiobesity drugs. The safety profile of this combination is acceptable, despite additional data regarding cardiovascular disease being needed. PMID:25258511

  6. Continuous direct compression as manufacturing platform for sustained release tablets.

    Science.gov (United States)

    Van Snick, B; Holman, J; Cunningham, C; Kumar, A; Vercruysse, J; De Beer, T; Remon, J P; Vervaet, C

    2017-03-15

    This study presents a framework for process and product development on a continuous direct compression manufacturing platform. A challenging sustained release formulation with high content of a poorly flowing low density drug was selected. Two HPMC grades were evaluated as matrix former: standard Methocel CR and directly compressible Methocel DC2. The feeding behavior of each formulation component was investigated by deriving feed factor profiles. The maximum feed factor was used to estimate the drive command and depended strongly upon the density of the material. Furthermore, the shape of the feed factor profile allowed definition of a customized refill regime for each material. Inline NIRs was used to estimate the residence time distribution (RTD) in the mixer and monitor blend uniformity. Tablet content and weight variability were determined as additional measures of mixing performance. For Methocel CR, the best axial mixing (i.e. feeder fluctuation dampening) was achieved when an impeller with high number of radial mixing blades operated at low speed. However, the variability in tablet weight and content uniformity deteriorated under this condition. One can therefore conclude that balancing axial mixing with tablet quality is critical for Methocel CR. However, reformulating with the direct compressible Methocel DC2 as matrix former improved tablet quality vastly. Furthermore, both process and product were significantly more robust to changes in process and design variables. This observation underpins the importance of flowability during continuous blending and die-filling. At the compaction stage, blends with Methocel CR showed better tabletability driven by a higher compressibility as the smaller CR particles have a higher bonding area. However, tablets of similar strength were achieved using Methocel DC2 by targeting equal porosity. Compaction pressure impacted tablet properties and dissolution. Hence controlling thickness during continuous manufacturing of

  7. Organically modified titania nanoparticles for sustained drug release applications.

    Science.gov (United States)

    Sethi, Komal; Roy, Indrajit

    2015-10-15

    In this paper, we report the synthesis, characterization of drug-doped organically modified titania nanoparticles, and their applications in sustained drug release. The drug-doped nanoparticles were synthesized in the hydrophobic core of oil-in-water microemulsion medium. Structural aspects obtained through TEM and FESEM depicted that organically modified titania nanoparticles are monodispersed with spherical morphology, with an average size of around 200 nm. Their polymorphic forms and porosity were determined using powder XRD and BET, respectively, which showed that they are present in the anatase form, with a surface area of 136.5 m(2)/g and pore-diameter of 5.23 nm. After synthesis and basic structural characterizations, optical properties were studied for both fluorophore and drug encapsulated nanoparticles. The results showed that though the optical properties of the fluorophore are partially diminished upon nanoencapsulation, it became more stable against chemical quenching. The nanoparticles showed pH-dependent drug release pattern. In vitro studies showed that the nanoparticles were efficiently uptaken by cells. Cell viability assay results showed that though the placebo nanoparticles are non-cytotoxic, the drug-doped nanoparticles show drug-induced toxicity. Therefore, such porous nanoparticles can be used in non-toxic drug delivery applications. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Naltrexone sustained-release/bupropion sustained-release for the management of obesity: review of the data to date

    Directory of Open Access Journals (Sweden)

    Caixàs A

    2014-09-01

    Full Text Available Assumpta Caixàs, Lara Albert, Ismael Capel, Mercedes Rigla Endocrinology and Nutrition Department, Parc Tauli Sabadell University Hospital, Autonomous University of Barcelona, Barcelona, Spain Abstract: Obesity is an emerging disease worldwide. Changes in living habits, especially with increased consumption of high-calorie foods and decreased levels of physical activity, lead to an energy imbalance that brings weight gain. Overweight and obesity are major risk factors for several chronic diseases (including cardiovascular diseases, diabetes, and cancer, reduce quality of life, and are associated with higher mortality. For all these reasons, it is of the utmost importance that the trend be reversed and obese people enabled to lose weight. It is known that eating a healthy diet and exercising regularly can help prevent obesity, but data show that in many cases these steps are not enough. This is the reason why, over the last few decades, several antiobesity drugs have been developed. However, the disappointing results demonstrated for the vast majority of them have not discouraged the pharmaceutical industry from continuing to look for an effective drug or combination of drugs. The systematic review presented here focuses on naltrexone sustained-release/bupropion sustained-release combination (Contrave®. We conclude from the current published reports that its effectiveness in the treatment of obesity can be estimated as a placebo-subtracted weight loss of around 4.5%. This weight reduction is moderate but similar to other antiobesity drugs. The safety profile of this combination is acceptable, despite additional data regarding cardiovascular disease being needed. Keywords: Contrave, weight loss, overweight, cardiovascular disease, diabetes, cancer

  9. A Prospective Survey on Safety of Sustained-Release Theophylline in Treatment of Asthma and COPD

    Directory of Open Access Journals (Sweden)

    Sohei Makino

    2006-01-01

    Conclusions: The present survey demonstrates that sustained-release theophylline is safe, as long as used appropriately, although adverse reactions tend to develop early after initiation of administration.

  10. Comparison of the efficacy of two anticonvulsants, phenytoin and valproate to improve PCP and d-amphetamine induced deficits in a reversal learning task in the rat

    Directory of Open Access Journals (Sweden)

    Nagi F Idris

    2009-06-01

    Full Text Available Recent studies in our laboratory have shown that PCP (phencyclidine and d-amphetamine induce a cognitive deficit in rats, in a paradigm of potential relevance for the pathology of schizophrenia. Atypical, but not classical antipsychotics and the anticonvulsant, lamotrigine have been shown to prevent a selective reversal learning deficit induced by PCP. In contrast, only haloperidol reversed the d-amphetamine-induced deficit. The present study aimed to explore the ability of two anticonvulsants with differing mechanism of action, valproate and phenytoin to attenuate the cognitive deficits induced by PCP and d-amphetamine in the reversal learning paradigm. PCP at 1.5mg/kg and d-amphetamine at 0.5mg/kg both produced a selective and significant reduction in performance of the reversal phase with no effect on the initial phase of the task in female-hooded Lister rats. Valproate (25-200mg/kg and phenytoin (25-50mg/kg had no effect on performance when administered alone. Valproate (100-200mg/kg, whose principle action is thought to be the enhancement of GABA transmission, was unable to prevent the cognitive deficit induced by either PCP or d-amphetamine. Conversely, phenytoin (50mg/kg, a use-dependent sodium channel inhibitor, significantly prevented the deficit induced by PCP, but not d-amphetamine. These results add to our earlier work with lamotrigine, and suggest that sodium channel blockade may be a mechanism by which some anticonvulsant drugs can prevent the PCP-induced deficit. These data have implications for the use of anticonvulsant drugs in the treatment of cognitive or psychotic disorders.

  11. [Preparation and evaluation of sustained-release microsphere of Sanguis Draconis in vitro].

    Science.gov (United States)

    Ding, Li-Yu; Xia, Peng-Fei; Yang, Cai-Qin; Lin, Yu-Long; Wang, Jing

    2007-03-01

    To prepare sustained-release microsphere containing extract of Sanguis Draconis and to measure its dissolution in vitro. Sustained-release microsphere was prepared with polylactic acid (PLA) as carriers using the oil-in-water (O/W) emulsion solvent evaporation method. The powder particle's characteristics of sustainded-release microsphere were evaluated comprehensively, and its dissolution characteristics in vitro were studied. The microsphere was round and its surface was smooth, drug-loading rate was 21.97% and the entrapment rate was 55.76%, the accumulative release percentage was 76. 71% in 16 hours. The sustained release effect of Sanguis Draconis microspheres was formed with potentially wide applications.

  12. Nanoparticle-based topical ophthalmic formulations for sustained celecoxib release.

    Science.gov (United States)

    Ibrahim, Mohammed Mostafa; Abd-Elgawad, Abd-Elgawad Helmy; Soliman, Osama Abd-Elazeem; Jablonski, Monica M

    2013-03-01

    Celecoxib-loaded NPs were prepared from biodegradable polymers such as poly-ε-caprolactone (PCL), poly(L-lactide) (PLA), and poly(D,L-lactide-co-glycolide) (PLGA) by spontaneous emulsification solvent diffusion method. Different concentrations of polymers, emulsifier, and cosurfactants were used for formulation optimization. Nanoparticles (NPs) were characterized regarding their particle size, PDI, zeta potential, shape, morphology, and drug content. Celecoxib-loaded NPs were incorporated into eye drops, in situ gelling system, and gel and characterized regarding their pH, viscosity, uniformity of drug content, in vitro release, and cytotoxicity. The results of optimized celecoxib-loaded PCL-, PLGA-, and PLA-NPs, respectively, are particle size 119 ± 4, 126.67 ± 7.08, and 135.33 ± 4.15 nm; zeta potential -22.43 ± 2.91, -25.46 ± 2.35, and -31.81 ± 2.54 mV; and encapsulation efficiency 93.44 ± 3.6%, 86.00 ± 1.67%, and 79.04 ± 2.6%. TEM analyses revealed that NPs have spherical shapes with dense core and distinct coat. Formulations possessed uniform drug content with pH and viscosity compatible with the eye. Formulations showed sustained release without any burst effect with the Higuchi non-fickian diffusion mechanism. Cytotoxicity studies revealed that all formulations are nontoxic. Our formulations provide a great deal of flexibility to formulation scientist whereby sizes and zeta potentials of our NPs can be tuned to suit the need using scalable and robust methodologies. These formulations can thus serve as a potential drug delivery system for both anterior and posterior eye diseases. Copyright © 2012 Wiley Periodicals, Inc.

  13. Formulation and In vitro/In vivo Evaluation of Sustained Release ...

    African Journals Online (AJOL)

    HP

    2013-07-15

    Jul 15, 2013 ... Purpose: To develop and optimise sustained release (SR) matrix tablets of diltiazem hydrochloride (DHL). Methods: ... Keywords: Diltiazem, Matrix tablet, Hydroxypropyl methylcellulose Eudragit, In vitro/in vivo correlation, Optimization. Tropical ..... Makhija S, Vavia P. Once daily sustained release tablets.

  14. D-amphetamine improves cognitive deficits and physical therapy promotes fine motor rehabilitation in a rat embolic stroke model

    DEFF Research Database (Denmark)

    Rasmussen, Rune Skovgaard; Overgaard, K; Hildebrandt-Eriksen, E S

    2006-01-01

    BACKGROUND AND PURPOSE: The purpose of this study was to examine the effects of D-amphetamine (D-amph) and physical therapy separately or combined on fine motor performance, gross motor performance and cognition after middle cerebral artery thromboembolization in rats. METHODS: Seventy-four rats......-amph), 4) THERAPY (embolized, saline + physical therapy) and 5) D-AMPH + THERAPY (embolized, D-amph + physical therapy). Rats of the groups 4-5 underwent d-amph or saline treatment on days 1, 3, 5 and 7 after surgery and were re-trained for 1 h starting 60 min after each treatment. During this time, rats...... regarding gross motor performance. CONCLUSIONS: After embolization, physical therapy improved fine motor performance and D-amph accelerated rehabilitation of cognitive performance as observed in the rats of the THERAPY and D-AMPH groups. As a result of the administration of a high dose of D-amph, the rats...

  15. Effects of the cannabinoid CB1 receptor agonist CP55,940 and antagonist SR141716A on d-amphetamine-induced behaviours in Cebus monkeys

    DEFF Research Database (Denmark)

    Madsen, Morten V; Peacock, Linda; Werge, Thomas

    2006-01-01

    ligands within and across species. The aim of the present study was to explore these contradictory findings in a non-human primate model, predictive of antipsychotic efficacy in humans. The effects of the cannabinoid CB1 receptor antagonist SR141716A and the CB1 receptor agonist CP55,940 were explored...... in an d-amphetamine-based Cebus monkey model of psychosis. The monkeys were sensitive to extrapyramidal side effects (EPS), and the side-effect profiles of the drugs were explored as well. SR141716A (0.1, 0.25, 0.375, 0.5 and 0.75 mg/kg) and CP55,940 (0.0025, 0.005 and 0.01 mg/kg) were administered...... by subcutaneous injection alone and in combination with d-amphetamine (0.25mg/kg). SR141716A (0.1-0.5mg/kg) reduced d-amphetamine-induced arousal, while CP55,940 had no significant effect upon d-amphetamine-induced behaviours. No EPS were observed with either of these compounds. These data suggest...

  16. Bioactive Glass Nanoparticles as a New Delivery System for Sustained 5-Fluorouracil Release: Characterization and Evaluation of Drug Release Mechanism

    Directory of Open Access Journals (Sweden)

    Abeer M. El-Kady

    2015-01-01

    Full Text Available Bioactive glass nanoparticles were synthesized and tested for the first time as a new delivery system for sustained 5-fluorouracil (5-FU release. They were characterized by TEM, DTA, TGA, and FT-IR. The porosity % and specific surface area of glass nanoparticles were 85.59% and 378.36 m2/g, respectively. The in vitro bioactivity evaluation confirmed that bioactive glass disks prepared from these nanoparticles could induce hydroxyapatite layer over their surfaces in simulated body fluid. The in vitro drug release experiment indicated that glass nanoparticles could serve as long-term local delivery vehicles for sustained 5-FU release. The release profile of 5-FU showed an initial fast release stage followed by a second stage of slower release. The initial burst release of 5-FU in the first day was about 23% (28.92 mg·L−1 of the total amount of loaded 5-FU, while the final cumulative percentage of the 5-FU released after 32 days was about 45.6% (57.31 mg·L−1 of the total amount of loaded 5-FU. The application of different mathematical models indicated that 5-FU was released by diffusion controlled mechanism and suggested that its release rate was dependent on glass particles dissolution, changes of surface area as well as diameter of glass particles, and concentration of loaded drug.

  17. Sustained Release of a Water-Soluble Drug from Directly ...

    African Journals Online (AJOL)

    Okra gum was evaluated as a controlled-release agent in modified release matrices in comparison with sodium carboxymethylcellulose (NaCMC) using aspirin as the model drug. Tablets were produced by direct compression and the in vitro drug release was assessed under conditions similar to those in the gastrointestinal ...

  18. Differential effects of D-amphetamine on red and blue light-induced photic activation: A novel BOLD fMRI assay of human dopamine function.

    Science.gov (United States)

    Cowan, Ronald L; Wood, Julia; Dietrich, Mary S; de B Frederick, Blaise; Lukas, Scott E; Renshaw, Perry F

    2008-04-01

    The neurotransmitter dopamine (DA) is implicated in the pathophysiology of central nervous system (CNS) illnesses including Parkinson's disease, attention deficit disorder, schizophrenia, and substance abuse. A better understanding of CNS DA function would be of importance in improving our understanding of these conditions. Several lines of evidence suggest that exploring visual system function may be a useful paradigm for examining DA function. Clinical and basic science findings suggest that the visual response to blue light might prove a useful assay of CNS DA tone. To test this hypothesis, we used the functional magnetic resonance imaging (fMRI) BOLD method to measure visual cortical activation in human subjects (N = 6) in response to 8 Hz flashing red and blue light stimuli during placebo conditions and during the oral administration of 2.5 mg of D-amphetamine, a drug known to increase synaptic concentrations of DA and other monoamine neurotransmitters. There was no effect of D-amphetamine administration on the percent BOLD signal change to red or blue light. However, there was a specific augmentation of the spatial extent of activation (as measured by the number of activated pixels; P = 0.018) to blue, but not red light following D-amphetamine administration. This finding is consistent with our hypothesis that blue light function may have utility as an assay of CNS DA tone. However, several limitations to the study, including the small sample size, low dosage of D-amphetamine, and the fact that D-amphetamine increases synaptic concentrations of DA and other monoamine neurotransmitters do not permit a conclusion regarding a specific role for DA in the observed increase in spatial activation to blue light in the amphetamine condition.

  19. Adolescent D-amphetamine treatment in a rodent model of ADHD: Pro-cognitive effects in adolescence without an impact on cocaine cue reactivity in adulthood.

    Science.gov (United States)

    Jordan, Chloe J; Taylor, Danielle M; Dwoskin, Linda P; Kantak, Kathleen M

    2016-01-15

    Attention-deficit/hyperactivity disorder (ADHD) is comorbid with cocaine abuse. Whereas initiating ADHD medication in childhood does not alter later cocaine abuse risk, initiating medication during adolescence may increase risk. Preclinical work in the Spontaneously Hypertensive Rat (SHR) model of ADHD found that adolescent methylphenidate increased cocaine self-administration in adulthood, suggesting a need to identify alternatively efficacious medications for teens with ADHD. We examined effects of adolescent d-amphetamine treatment on strategy set shifting performance during adolescence and on cocaine self-administration and reinstatement of cocaine-seeking behavior (cue reactivity) during adulthood in male SHR, Wistar-Kyoto (inbred control), and Wistar (outbred control) rats. During the set shift phase, adolescent SHR needed more trials and had a longer latency to reach criterion, made more regressive errors and trial omissions, and exhibited slower and more variable lever press reaction times. d-Amphetamine improved performance only in SHR by increasing choice accuracy and decreasing errors and latency to criterion. In adulthood, SHR self-administered more cocaine, made more cocaine-seeking responses, and took longer to extinguish lever responding than control strains. Adolescent d-amphetamine did not alter cocaine self-administration in adult rats of any strain, but reduced cocaine seeking during the first of seven reinstatement test sessions in adult SHR. These findings highlight utility of SHR in modeling cognitive dysfunction and comorbid cocaine abuse in ADHD. Unlike methylphenidate, d-amphetamine improved several aspects of flexible learning in adolescent SHR and did not increase cocaine intake or cue reactivity in adult SHR. Thus, adolescent d-amphetamine was superior to methylphenidate in this ADHD model. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. Sustained-Release Permanganate: Passive Reactive Barriers for Green and Sustainable Remediation

    Science.gov (United States)

    Dugan, P. J.

    2011-12-01

    Reactive materials in permeable reactive barriers (PRBs) have proven very useful for transforming or destroying organic waste in situ. Once emplaced they typically do not require a continued supply of electrical power and have the added benefit of creating a reactive zone for the destruction of contaminants in place. Controlled-release techniques have been utilized extensively in diverse fields such as pharmaceutical and agrochemical technologies. However, controlled- and sustained release of an oxidant during in situ chemical oxidation (ISCO) is an emerging concept that is extremely relevant to the field of environmental remediation, yet to-date has received little attention. ISCO using the oxidants permanganate, persulfate, and catalyzed hydrogen peroxide has shown great promise for remediation of many recalcitrant organic contaminants of concern (COC). Because the oxidant also reacts with natural organic matter, inorganic soil constituents, and other reduced compounds, the presence of a protective barrier that controls oxidant release may enhance the efficiency of ISCO and allow for long-term low-cost treatment of chlorinated solvents. To this end, sustained-release permanganate (SRP) was developed. Paraffin wax was used as the environmentally benign and biodegradable matrix material for encapsulating the solid potassium permanganate (KMnO4) particles. The paraffin matrix protects the solid KMnO4 particles from fast dissolution and potentially undesirable nonproductive reactions. The SRP material contains between 60%-80% permanganate and can be formed as candles for direct push applications in reactive barriers, or chipped material for hydro-fracturing into low permeability media. One-dimensional (1-D) SRP column experiments were conducted to evaluate permanganate release behavior using deionized (DI) water as the influent or COC removal efficiency using dissolved trichloroethene (TCE) as the influent. The influent dissolved TCE concentrations were 1 mg/L and

  1. Effect of different polymers and their combinations on the release of metoclopramide HCl from sustained-release hydrophilic matrix tablets.

    Science.gov (United States)

    Savaşer, Ayhan; Taş, Çetin; Bayrak, Ziya; Özkan, Cansel Köse; Özkan, Yalçın

    2013-01-01

    Metoclopramide HCl (MTC) is commonly used for the management of gastrointestinal disorders. It has a short biological half-life and is usually administered four times daily to maintain effective concentrations throughout the day. The aim of this study is to develop sustained-release hydrophilic matrix tablet formulations of drug to achieve reproducible and predictable release rates, extended duration of activity, decreased toxicity, reduction of required dose, optimized therapy, and improved patient compliance. Hydroxypropylmethyl cellulose (HPMC), carboxymethylcellulose sodium (NaCMC), chitosan and Carbopol 981 were incorporated in the matrix system separately or in combinations as release controlling factor by direct compression technique. Compatibility among the formulation components was assessed by DSC and FTIR analysis. MTC release from matrix was evaluated by using the US Pharmacopeia dissolution apparatus II. All formulations met the criteria of pharmacopeial requirements. Dissolution studies show that polymer type and concentration are important parameters on drug release. Chitosan, carbopol and NaCMC formulations exhibited pH-dependent drug release profile whereas HPMC did not. All the formulations containing 1:1 ratio of HPMC and chitosan exhibited desired drug release showing that all active substance releases progressively in a period of whole dissolution time and therefore it can be regarded as worthy of consideration for the manufacture of sustained-release MTC product.

  2. Comparison of gastroretentive microspheres and sustained-release preparations using theophylline pharmacokinetics.

    Science.gov (United States)

    Miyazaki, Yasunori; Yakou, Shigeru; Takayama, Kozo

    2008-06-01

    The objective of this study was to use the pharmacokinetics of theophylline to compare various gastroretentive microspheres. Three types of theophylline microspheres prepared from a hydrophobic dextran derivative were characterized in terms of drug release in-vitro and floating and mucoadhesive properties. Theophylline pharmacokinetic studies were conducted in Beagle dogs, comparing bulk powder, commercial sustained-release granules (Theodur), sustained-release microspheres, floatable microspheres and mucoadhesive microspheres. Theodur and sustained-release microspheres resulted in a lower maximum concentration (Cmax) (P mucoadhesive microspheres indicated an increase in AUC without decreasing the rate of bioavailability. Overall, the gastroretentive microspheres improved the extent of bioavailability of theophylline, which is absorbable from the entire gastrointestinal tract. The mucoadhesive microsphere showed a prolonged serum drug level, indicating a superior sustained-release delivery system for theophylline.

  3. Evaluation of dibutyrylchitin as new excipient for sustained drug release.

    Science.gov (United States)

    Casettari, Luca; Cespi, Marco; Castagnino, Enzo

    2012-08-01

    Dibutyrylchitin (DBC), a lipophilic chitin diester, has been synthesized from chitin and butyric anhydride with methanesulfonic acid as catalyst. Exhaustive esterification of free alcoholic groups of chitin was assessed by FT-IR and (1)H-NMR spectroscopy. High degree of alkyl substitution allowed DBC to acquire an almost completely lipophilic character. Tablets of paracetamol and metformin employing DBC as major excipient, in comparison with starch, microcrystalline cellulose, lactose and polyvinylpyrrolidone, were prepared and rates of drug release were checked by dissolution test assays. DBC released drug at a lower rate than that of the other tested materials. A comparison study of rate release of metformin from DBC tablets and from metformin-hydroxypropyl methylcellulose prolonged release oral formulation available on the market has been also curried out. Under the same conditions and in the presence of the same amount of loaded drug, DBC released 64% of metformin whereas hypromellose-based tablets released 87%.

  4. Sustainability, Biodiversity and Ethical Aspects of Deliberate Release of GMOs

    DEFF Research Database (Denmark)

    Agger, Peder Winkel

    2006-01-01

    Sustainable development is a way to organize complex political issues at a higher level where both natural scientific rationality and normative based arguments may be parts of a more coherent comprehension.......Sustainable development is a way to organize complex political issues at a higher level where both natural scientific rationality and normative based arguments may be parts of a more coherent comprehension....

  5. Letter to the editor: naltrexone sustained-release/bupropion sustained-release for the management of obesity: review of the data to date

    Directory of Open Access Journals (Sweden)

    Buehler AM

    2015-01-01

    Full Text Available Anna M Buehler Hospital Alemao Oswaldo Cruz, Institute of Health Education and Sciences, Sao Paulo, BrazilI read with great interest the systematic review by Caixàs et al1 on the effect of naltrexone sustained-release/bupropion sustained-release (NB for the management of obesity. By comprehensively appraising five recent clinical trials, the authors concluded that the naltrexone/bupropion combination might represent an important new therapeutic option for the management of obesity, with a weight reduction effect that is similar to other drugs approved for the treatment of obesity.View original paper by Caixàs and colleagues.

  6. Biodegradable Injectable In Situ Implants and Microparticles for Sustained Release of Montelukast: In Vitro Release, Pharmacokinetics, and Stability

    OpenAIRE

    Ahmed, Tarek A.; Ibrahim, Hany M.; Ahmed M Samy; Kaseem, Alaa; Nutan, Mohammad T. H.; Hussain, Muhammad Delwar

    2014-01-01

    The objective of this study was to investigate the sustained release of a hydrophilic drug, montelukast (MK), from two biodegradable polymeric drug delivery systems, in situ implant (ISI) and in situ microparticles (ISM). N-Methyl pyrrolidone (NMP), dimethyl sulfoxide (DMSO), triacetin, and ethyl acetate were selected as solvents. The release of 10% (w/v) MK from both systems containing poly-lactic-co-glycolic acid (PLGA) as the biodegradable polymer was compared. Upon contact with the aqueou...

  7. Pharmacokinetics of nifedipine slow-release during sustained tocolysis

    NARCIS (Netherlands)

    ter Laak, Maureen A.; Roos, Carolien; Touw, Daan J.; van Hattum, Paul R. M.; Kwee, Anneke; Lotgering, Frederik K.; Mol, Ben Willem J.; van Pampus, Mariëlle G.; Porath, Martina M.; Spaanderman, Marc E. A.; van der Post, Joris A. M.; Papatsonis, Dimitri N. M.; van 't Veer, Nils E.

    2015-01-01

    The pharmacokinetics of nifedipine as a tocolytic agent has not been studied in great detail in pregnant women and has instead focused on immediate release tablets and gastrointestinal therapeutic system (GITS) tablets. The aim of this study was to determine nifedipine slow-release half-life and

  8. Pharmacokinetics of nifedipine slow-release tablets during sustained tocolysis

    NARCIS (Netherlands)

    ter Laak, Maureen A.; Roos, Carolien; Touw, Daan J.; van Hattum, Paul R. M.; Kwee, Anneke; Lotgering, Frederik K.; Moi, Ben Willem J.; van Pampus, Marielle G.; Porath, Martina M.; Spaanderman, Marc E. A.; van der Post, Joris A. M.; Papatsonis, Dimitri N. M.; van 't Veer, Nils E.

    Objective: The pharmacokinetics of nifedipine as a tocolytic agent has not been studied in great detail in pregnant women and has instead focused on immediate release tablets and gastrointestinal therapeutic system (GITS) tablets. The aim of this study was to determine nifedipine slow-release

  9. Formulation of Sustained-Release Matrix Tablets Using Cross ...

    African Journals Online (AJOL)

    Matrix tablets of DTZ were prepared using varying ratios of unmodified karaya gum (K) and MK by direct compression. The matrix tablets were evaluated for pharmacotechnical properties and in vitro release, including release kinetics. The optimized formulation was compared with Dilzem SR which served as reference.

  10. Development and evaluation of sustained release losartan potassium matrix tablet using kollidon SR as release retardant

    Directory of Open Access Journals (Sweden)

    Shahid Sarwar

    2012-12-01

    Full Text Available The present study was undertaken to develop sustained release (SR matrix tablets of losartan potassium, an angiotensin-II antagonist for the treatment of hypertension. The tablets were prepared by direct compression method, along with Kollidon SR as release retardant polymer. The amount of losartan potassium remains fixed (100 mg for all the three formulations whereas the amounts of Kollidon SR were 250 mg, 225 mg, and 200 mg for F-1, F-2, and F-3 respectively. The evaluation involves three stages: the micromeritic properties evaluation of granules, physical property studies of tablets, and in-vitro release kinetics studies. The USP apparatus type II was selected to perform the dissolution test, and the dissolution medium was 900 mL phosphate buffer pH 6.8. The test was carried out at 75 rpm, and the temperature was maintained at 37 ºC ± 0.5 ºC. The release kinetics was analyzed using several kinetics models. Higher polymeric content in the matrix decreased the release rate of drug. At lower polymeric level, the rate and extent of drug release were enhanced. All the formulations followed Higuchi release kinetics where the Regression co-efficient (R² values are 0.958, 0.944, and 0.920 for F-1, F-2, and F-3 respectively, and they exhibited diffusion dominated drug release. Statistically significant (PO presente estudo foi realizado para desenvolver (SR matriz de comprimidos de liberação sustentada de losartana, um antagonista da angiotensina II, para o tratamento da hipertensão arterial. Os comprimidos foram preparados pelo método de compressão direta com Kollidon SR como polímero de liberação lenta. A quantidade de losartana potássica permanece fixa (100 mg para todas as três formulações enquanto que as quantidades de Kollidon SR foram de 250 mg, 225 mg e 200 mg para F-1, F-2 e F-3, respectivamente. A avaliação envolve três etapas- propriedades micromeríticas dos grânulos, estudo das propriedades físicas dos comprimidos e

  11. Paradoxical effects of D-amphetamine in infant and adolescent mice: role of gender and environmental risk factors.

    Science.gov (United States)

    Cirulli, F; Laviola, G

    2000-01-01

    The psychostimulant D-amphetamine (AMPH) increases generalised activity in adult subjects, while exerting a paradoxical "calming effect" in children with Attention-deficit Hyperactivity Disorder (AD/HD). A number of animal models have been developed to characterise the neurobiological basis of this AMPH action. In this line, the present review summarises recent work on the effects of AMPH on behavioural and physiological parameters in developing mice with a special emphasis on the role of gender and environmental risk factors. Behavioural and neuroendocrine responses to AMPH administration (0, 1, or 3 mg/kg, IP) and their relation to changes in the environment, represented by social stimuli, were studied in infant CD-1 mouse pups of both sexes at three different developmental ages (3, 8, or 18 postnatal (pnd) days). Mouse pups were assessed either in baseline condition or following 24 h maternal deprivation. AMPH exerted a paradoxical effect on CORT secretion only in maternally deprived subjects while affecting behaviour mainly in deprived female subjects, which showed a generalised shift to the left in the dose-response curve to this drug. Unwanted perseverative motor effects and possible dependence states represent side effects of AMPH administration. Further knowledge on these aspects comes from another set of studies where a shortened conditioned place preference (CPP) paradigm was employed to assess the reinforcing properties of AMPH (0, 1, 3.3, or 10 mg/kg) in developing mice on 14-17, 21-24, and 28-31 pnd. Data indicate that AMPH-CPP develops early, mice being able, already at two weeks of age, to acquire a place preference that relies on adult-like sensory, motor, and associative capacities. AMPH-CPP appears earlier in females, compared to males. A detailed analysis of acute D-amphetamine effects evidenced that the drug produces a dose-dependent increase in locomotor activity and in several responses (including stereotypes). These effects appear much larger

  12. Formulation and evaluation of sustained release enteric-coated pellets of budesonide for intestinal delivery

    National Research Council Canada - National Science Library

    Raval, Mihir K; Ramani, Riddhi V; Sheth, Navin R

    2013-01-01

    ...) full factorial design by giving an enteric coating with Eudragit S100. Budesonide-sustained release pellets were prepared by extruder and spheronization technique using a combination of water-soluble and permeable polymers by applying 3(2...

  13. Diclofenac transdermal patch versus the sustained release tablet: A ...

    African Journals Online (AJOL)

    Conclusion: Transdermal films of diclofenac, formulated with permeation enhancers, may have greater therapeutic advantages over conventional oral tablets in terms of prolonged release and improvement of patient compliance in rheumatoid arthritis. Keywords: Analgesic activity, Diclofenac, Permeation enhancer, ...

  14. Pharmacokinetics and in vivo scintigraphic monitoring of a sustained release acetylsalicylic acid formulation

    Energy Technology Data Exchange (ETDEWEB)

    Wilson, C.G.; Hardy, J.C. (Queen' s Medical Centre, Nottingham (UK)); Parr, G.D.; Kennerley, J.W.; Taylor, M.J.; Davis, S.S. (Nottingham Univ. (UK)); Rees, J.A. (Boots Research Laboratories, Nottingham (UK))

    1984-01-01

    The in vivo dissolution and pharmacokinetics of a sustained release aspirin formulation labelled with (sup(99m)Tc)diethylenetriaminepentaacetic acid has been monitored in 5 subjects by the use of gamma scintigraphy and drug analysis undertaken of blood and urine samples. The data obtained enabled the position of the tablet in vivo to be related to the plasma and urinary salicylate levels. The study confirms the sustained release properties of the cellulose acetate phthalate formulation.

  15. Sustained release myofascial release as treatment for a patient with complications of rheumatoid arthritis and collagenous colitis: a case report.

    Science.gov (United States)

    Cubick, Erin E; Quezada, Vanessa Y; Schumer, Ariel D; Davis, Carol M

    2011-01-01

    Myofascial release (MFR) is a manual therapeutic technique used to release fascial restrictions, which may cause neuromusculoskeletal and systemic pathology. This case report describes the use of sustained release MFR techniques in a patient with a primary diagnosis of rheumatoid arthritis (RA) and a secondary diagnosis of collagenous colitis. Changes in pain, cervical range of motion, fatigue, and gastrointestinal tract function, as well as the impact of RA on daily activities, were assessed. A 54-year-old white woman presented with signs and symptoms attributed to RA and collagenous colitis. Pre and post measurements were taken with each treatment and during the interim between the initial and final treatment series. The patient recorded changes in pain, fatigue, gastrointestinal tract function, and quality of life. Cervical range of motion was assessed. Six sustained release MFR treatment sessions were provided over a 2-week period. Following an 8-week interim, two more treatments were performed. The patient showed improvements in pain, fatigue, gastrointestinal tract function, cervical range of motion, and quality of life following the initial treatment series of six sessions. The patient maintained positive gains for 5 weeks following the final treatment, after which her symptoms returned to near baseline measurements. Following two more treatments, positive gains were achieved once again. In a patient with RA and collagenous colitis, the application of sustained release MFR techniques in addition to standard medical treatment may provide short-term and long-term improvements in comorbid symptoms and overall quality of life.

  16. Acute inhalation exposure to cyclohexane and schedule-controlled operant performance in rats: comparison to d-amphetamine and chlorpromazine.

    Science.gov (United States)

    Christoph, G R; Kelly, D P; Krivanek, N

    2000-11-01

    Adult male rats pressed a lever on a multiple fixed ratio-fixed interval (FR20-FI120 sec) schedule of food presentation, and after attaining a stable baseline subjects received an acute inhalation exposure to cyclohexane vapor (0 ppm, 500 ppm, 2000 ppm, or 7000 ppm) for 6 hr. During the operant session that began 30 min after termination of exposure, FR running rate for the 7000 ppm group decreased 11% relative to performance on the previous day. FR post-reinforcement pause duration and the rate and pattern of FT performance were unaffected. Cyclohexane exposures of 500 or 2000 ppm had no detectable effects. No enduring effects of cyclohexane occurred up to 2 weeks after exposure. An independent set of rats, trained under nominally identical conditions, received various doses (i.p.) of d-amphetamine (AMPH) or chlorpromazine (CPZ) at 1-2 week intervals. Effective doses of AMPH decreased FR running rate, decreased FR post-reinforcement pause duration and increased FI rate of response. AMPH also decreased the FI index of curvature, indicating a change from an accelerating rate during the FI to a more constant rate. Effective doses of CPZ decreased FR rate, increased FR pause duration, decreased FI rate, and decreased FI index of curvature. Thus, schedule-controlled operant procedures that were sensitive to the effects of psychoactive drugs were able to identify only a minor and transient effect of the highest concentration (7000 ppm) of cyclohexane vapor on operant performance.

  17. Sustained Release of a Water~§oiuble itrng i'rom Directly ...

    African Journals Online (AJOL)

    desirable properties have encouraged a more extensive assessment of the gum as a hydrophilic controlled release delivery system. The aim of this study was to evaluate the gum extracted from the pods of Hibiscus esculentus. (commonly known as okra) in in vitro sustained release formulations containing the water-.

  18. Use of dika fat in the formulation of sustained release theophylline ...

    African Journals Online (AJOL)

    Sustained release theophylline tablets and capsules were prepared with dika fat, a solid vegetable oil extracted from the kernels of Irvingia gabonesis var gabonesis and var excelsia. Anhydrous theophylline was incorporated into dika fat by the fusion method. The in vitro release of the theophylline was monitored by the ...

  19. Preparation in high-shear mixer of sustained-release pellets by melt pelletisation.

    Science.gov (United States)

    Voinovich, D; Moneghini, M; Perissutti, B; Filipovic-Grcic, J; Grabnar, I

    2000-08-10

    The preparation of sustained-release pellets by melt pelletisation was investigated in a 10-l high shear mixer and ternary mixtures containing stearic acid as a melting binder, anhydrous lactose as a filler and theophylline as a model drug. A translated Doehlert matrix was applied for the optimisation of process variables and quality control of pellets characteristics. After determination of size distribution, the pellets were characterised with scanning electron microscopy, X-ray photoelectron spectroscopy and porosimetric analysis. Finally, the in vitro release from every single size fraction was evaluated and the release mechanism was analysed. Since the drug release rate decreased when enhancing the pellet size fraction, the 2000-microm fraction, exhibiting a substantially zero-order release, was selected for further in vivo biovailability studies. These data demonstrated that pellets based on the combination of stearic acid and lactose can be used to formulate sustained release pellets for theophylline.

  20. Separate and combined impact of acute naltrexone and alprazolam on subjective and physiological effects of oral d-amphetamine in stimulant users

    Science.gov (United States)

    Marks, Katherine R.; Lile, Joshua A.; Stoops, William W.

    2014-01-01

    Rationale Opioid antagonists (e.g., naltrexone) and positive modulators of γ-aminobutyric-acidA (GABAA) receptors (e.g., alprazolam) modestly attenuate the abuse-related effects of stimulants like amphetamine. The use of higher doses to achieve greater efficacy is precluded by side effects. Combining naltrexone and alprazolam might safely maximize efficacy while avoiding the untoward effects of the constituent compounds. Objectives The present pilot study tested the hypothesis that acute pretreatment with the combination of naltrexone and alprazolam would not produce clinically problematic physiological effects or negative subjective effects and would reduce the positive subjective effects of d-amphetamine to a greater extent than the constituent drugs alone. Methods Eight nontreatment-seeking, stimulant-using individuals completed an outpatient experiment in which oral d-amphetamine (0, 15, and 30 mg) was administered following acute pretreatment with naltrexone (0 and 50 mg) and alprazolam (0 and 0.5 mg). Subjective effects, psychomotor task performance, and physiological measures were collected. Results Oral d-amphetamine produced prototypical physiological and stimulant-like positive subjective effects (e.g., VAS ratings of Active/Alert/Energetic, Good Effect, and High). Pretreatment with naltrexone, alprazolam, and their combination did not produce clinically problematic acute physiological effects or negative subjective effects. Naltrexone and alprazolam each significantly attenuated some of the subjective effects of d-amphetamine. The combination attenuated a greater number of subjective effects than the constituent drugs alone. Conclusions The present results support the continued evaluation of an opioid receptor antagonist combined with a GABAA-positive modulator using more clinically relevant experimental conditions like examining the effect of chronic dosing with these drugs on methamphetamine self-administration. PMID:24464531

  1. Diclofenac transdermal patch versus the sustained release tablet: A ...

    African Journals Online (AJOL)

    therapeutic advantages over conventional oral tablets in terms of prolonged release and improvement of ... arthritic therapy. Non-steroidal anti-inflammatory drugs (NSAIDs) are prescribed frequently for the management of pain and local inflammation. (similar to gout) [5]. ... systems, transdermal films/patches are the most.

  2. Alginate-Chitosan Particulate System for Sustained Release of ...

    African Journals Online (AJOL)

    Erah

    Available online at http://www.tjpr.org. Research Article ... diffraction (XRD), and atomic absorption spectroscopy (AAS) were also applied to investigate the physicochemical characteristics of the drug in ... Both calcium alginate beads and the beads treated with chitosan failed to release the drug at pH 1.2 over the period of ...

  3. Pharmacokinetics of nifedipine slow-release during sustained tocolysis

    NARCIS (Netherlands)

    Laak, M.A. Ter; Roos, C.; Touw, D.J.; Hattum, P.R. van; Kwee, A.; Lotgering, F.K.; Moi, B.W.J.; Pampus, M.G. van; Porath, M.M.; Spaanderman, M.E.; Post, J.A. van der; Papatsonis, D.N.; Veer, N.E. van 't

    2015-01-01

    OBJECTIVE: The pharmacokinetics of nifedipine as a tocolytic agent has not been studied in great detail in pregnant women and has instead focused on immediate release tablets and gastrointestinal therapeutic system (GITS) tablets. The aim of this study was to determine nifedipine slowrelease

  4. Pharmacokinetics of nifedipine slow-release tablets during sustained tocolysis

    NARCIS (Netherlands)

    Ter Laak, Maureen A.; Roos, Carolien; Touw, Daan J.; Van Hattum, Paul R M; Kwee, Anneke|info:eu-repo/dai/nl/290465648; Lotgering, Frederik K.; Mol, Ben Willem J; Van Pampus, Mariëlle G.; Porath, Martina M.; Spaanderman, Marc E A; Van Der Post, Joris A M; Papatsonis, Dimitri N M; Van'T Veer, Nils E.

    2015-01-01

    Objective: The pharmacokinetics of nifedipine as a tocolytic agent has not been studied in great detail in pregnant women and has instead focused on immediate release tablets and gastrointestinal therapeutic system (GITS) tablets. The aim of this study was to determine nifedipine slowrelease

  5. Performance Evaluation of Marketed Brands of Sustained Release ...

    African Journals Online (AJOL)

    Statistical tests such as repeated ANOVA, Friedman test, Friedman ANOVA, Kendall's coefficient of concordance and Tukey-Kramer multiple comparison tests were applied on the range of data obtained from different brands. The results indicated non-significant differences in physical parameters and in vitro drug release, ...

  6. Formulation of Sustained-Release Diltiazem Matrix Tablets Using ...

    African Journals Online (AJOL)

    Methods: Matrix tablets of DTZ were prepared at different ratios of drug:gum (1:1, 1:2, and 1:4) and of the gum blends (K, K/LB, K/H and K/LB/H) by direct compression. The matrix tablets were evaluated for hardness, friability, in vitro release and drug content. The formulations were also characterised by scanning electron ...

  7. Preparation and Application of Sustained-Release Potassium Ferrate(VI

    Directory of Open Access Journals (Sweden)

    Xuan Xu

    2014-01-01

    Full Text Available In this study, a composite system for the sustained release of potassium ferrate(VI (sustained-release K2FeO4 was prepared and applied for water treatment. The objective of this research was to maximize the effectiveness of K2FeO4 for water treatment by enhancing its stability using diatomite. The sustained-release K2FeO4 was characterized using X-ray diffraction, scanning electron microscopy, and Fourier transform infrared spectroscopy. The results indicated that no new crystal phase was formed during the preparation and some K2FeO4 crystals entered the pores of the diatomite. From K2FeO4 release experiments, we found that the decomposition rate of K2FeO4 was obviously decreased, which greatly improved the contact rate between released K2FeO4 and pollutants. Via degradation of methyl orange, which was used as a model pollutant, the influential factor of K2FeO4 content within the complete sustained-release K2FeO4 system was studied. The optimal K2FeO4 content within the sustained-release K2FeO4 system was approximately 70%. In natural water samples, sustained-release K2FeO4 at a dosage of 0.06 g/L and with a reaction time of 20 minutes removed 36.84% of soluble microbial products and 17.03% of simple aromatic proteins, and these removal rates were better than those observed after traditional chlorine disinfection.

  8. Sustained release formulations of citronella oil nanoemulsion using cavitational techniques.

    Science.gov (United States)

    Agrawal, Naveen; Maddikeri, Ganesh L; Pandit, Aniruddha B

    2017-05-01

    Nanoemulsion synthesis has proven to be an effective way for transportation of immobile, insoluble bioactive compounds. Citronella Oil (lemongrass oil), a natural plant extract, can be used as a mosquito repellent and has less harmful effects compared to its available market counterpart DEET (N, N-Diethyl-meta-toluamide). Nanoemulsion of citronella oil in water was prepared using cavitation-assisted techniques while investigating the effect of system parameters like HLB (Hydrophilic Lipophilic Balance), surfactant concentration, input energy density and mode of power input on emulsion quality. The present work also examines the effect of emulsification on release rate to understand the relationship between droplet size and the release rate. Minimum droplet size (60nm) of the emulsion was obtained at HLB of 14, S/O1 ratio of 1.0, ultrasound amplitude of 50% and irradiation time of 5min. This study revealed that hydrodynamic cavitation-assisted emulsification is more energy efficient compared to ultrasonic emulsification. It was also found that the release rate of nanoemulsion enhanced as the droplet size of emulsion reduced. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Development of sustained-release matrix tablets of BKP-01-041 (tilorone derivative) containing Hypromellose.

    Science.gov (United States)

    Chen, Liangmei; Wang, Fei

    2013-10-01

    The objective of this research was to develop and evaluate sustained-release matrix tablets of BKP-01-041 (tilorone derivative) based on Hypromellose (hydroxypropyl methylcellulose, HPMC) as the matrix forming polymer. The sustained-release tablets were prepared by the wet granulation method. The influence of HPMC viscosity and ratios on drug release was investigated in vitro. Dissolution of the tablets developed with 26% HPMC K4 M/K100 M (1:2) (w/w) content showed a better drug release profile than the other batches tested in 12 h. Drug release from the optimal formulation was analyzed using release kinetics equations. The release kinetics parameters were determined and the value of the exponent (n) representing the apparent drug release mechanism determined from the Peppas equation was about 0.726. These results suggest that the drug release mechanism was non-Fickian (0.45 < n < 0.89), and drug release was dependent on both drug diffusion and polymer erosion.

  10. Sustained-release drug delivery of antimicrobials in controlling of supragingival oral biofilms.

    Science.gov (United States)

    Steinberg, Doron; Friedman, Michael

    2017-04-01

    Dental caries, a bacterial biofilm-associated disease, is a prevalent oral health problem. It is a bacterial biofilm-associated disease. Conventional means of combating this disease involves oral hygiene, mostly tooth brushing. Supplementary means of prevention and treatment is often necessary. The use of sustained-release delivery systems, locally applied to the oral cavity appears to be one of the most acceptable avenues for the delivery of antimicrobial agents. Area covered: The development and current approaches of local sustained delivery technologies applied to the oral cavity for treatment and prevention of dental caries is discussed. The use of polymeric drug delivery systems, varnishes, liposomes and nanoparticles is presented. Expert opinion: The use of local sustained-release delivery systems applied to the oral cavity has numerous clinical, pharmacological and toxicological advantages over conventional means. Various sustained-release technologies have been suggested over the course of several years. The current research on oral diseases concentrates predominantly on improving the drug delivery. With progress in pharmaceutical technology, sophisticated controlled-release platforms are being developed. The sustained release concept is innovative and there are few products available for the benefit of all populations. Harmonizing academic research with the dental industry will surely expedite the development and commercialization of more products of such pharmacological nature.

  11. Poly(lactide-co-glycolide) encapsulated hydroxyapatite microspheres for sustained release of doxycycline

    Energy Technology Data Exchange (ETDEWEB)

    Wang Xiaoyun [School of Pharmacy, Shenyang Pharmaceutical University, 103, Wenhua Road, Shenyang 110016 (China); Department of Pharmacy, Shandong Drug and Food Vocational College, Science and Technology Town, Hightech Industrial Development Zone, Weihai 264210 (China); Xu Hui; Zhao Yanqiu [School of Pharmacy, Shenyang Pharmaceutical University, 103, Wenhua Road, Shenyang 110016 (China); Wang Shaoning, E-mail: wsn-xh@126.com [School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, 103, Wenhua Road, Shenyang 110016 (China); Abe, Hiroya; Naito, Makio [Joining and Welding Research Institute, Osaka University, 11-1, Mihogaoka, Ibaraki, Osaka 567-0047 (Japan); Liu Yanli [School of Pharmacy, Shenyang Pharmaceutical University, 103, Wenhua Road, Shenyang 110016 (China); Wang Guoqing [School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, 103, Wenhua Road, Shenyang 110016 (China)

    2012-03-15

    Highlights: Black-Right-Pointing-Pointer PLGA encapsulated HAP-MSs were used for the sustained delivery of Doxycycline (Doxy, a broad spectrum tetracycline antibiotic). Black-Right-Pointing-Pointer Sustained Doxy release without obvious burst was observed. Black-Right-Pointing-Pointer Mechanism of the sustained Doxy release was illustrated. Black-Right-Pointing-Pointer Sustained Doxy release character in vivo was also obtained, the plasma Doxy levels were relatively lower and steady compared to that of the un-encapsulated HAP-MSs. - Abstract: The purpose of this study was to prepare a poly(lactide-co-glycolide) (PLGA) encapsulated hydroxyapatite microspheres (HAP-MSs) as injectable depot for sustained delivery of Doxycycline (Doxy). Doxy loaded HAP-MSs (Doxy-HAP-MSs) were encapsulated with PLGA by solid-in-oil-in-water (S/O/W) emulsion-solvent evaporation technique, the effects of the PLGA used (various intrinsic viscosity and LA/GA ratio) and ratio of PLGA/HAP-MSs on the formation of Doxy-HAP-MSs and in vitro release of Doxy were studied. The results showed that sustained drug release without obvious burst was obtained by using PLGA encapsulated HAP-MSs as the carrier, also the drug release rate could be tailored by changing the ratio of PLGA/HAP-MSs, or PLGA of various intrinsic viscosities or LA/GA ratio. Lower ratio of PLGA/HAP-MSs corresponded faster Doxy release, e.g. for the microspheres of PLGA/HAP-MSs ratio of 8 and 0.25, the in vitro Doxy release percents at the end of 7days were about 23% and 76%, respectively. Higher hydrophilicity (higher ratio of GA to LA) and lower molecular weight of PLGA corresponded to higher Doxy release rates. For in vivo release study, PLGA encapsulated HAP-MSs were subcutaneously injected to the back of mice, and the results showed good correlation between the in vivo and in vitro drug release. Meanwhile, the plasma Doxy levels after subcutaneous administration of PLGA encapsulated Doxy-HAP-MSs were relatively lower and steady

  12. Radiation crosslinked hydrogels as sustained release drug delivery systems

    Energy Technology Data Exchange (ETDEWEB)

    Pekala, W.; Rosiak, J.; Rucinska-Rybus, A.; Burczak, K.; Galant, S.; Czolczynska, T.

    1986-01-01

    Radiation methods have been used for: i/modification of vascular prostheses, ii/ obtaining burn dressing materials enabling controlled drug release, iii/ the preparation of polymer ocular insert discs. The surface of polyester vascular prostheses, has been modified by deposition of acrylamide and inducing its polymerization in the solid state by ..gamma..-radiation. As a result of this treatment, tightness of the prosthesis walls and its surface hydrophilicity have been improved. Toxicological examinations and blood hemolysis studies of modified prostheses showed its good biocompatibility. Various burn dressings have been prepared and the most promising of all investigated turned to be composition consisting of a cotton gauze base and an active polyacrylamide hydrogel layer with addition of glycerin and immobilized Provital/protein preparation/. Preliminary clinical evaluations of this particular dressing showed that the process of burn healing is indeed fast and fully satisfactory. Ocular insert discs made of polymer and containing pilocarpin hydrochloride which is released at controlled rate have been prepared. It has been found that high hydrophilicity and good swelling properties of the ocular insert discs made possible to incorporate pilocarpin hydrochloride into hydrogel matrix. This work has been carried out under IAEA research contract RB 3379/R-1 POL.

  13. Radiation crosslinked hydrogels as sustained release drug delivery systems

    Science.gov (United States)

    Pȩkala, W.; Rosiak, J.; Rucińska-Rybus, A.; Burczak, K.; Galant, S.; Czołlczyńska, T.

    Radiation methods have been used for: i/ modification of vascular prostheses, ii/ obtaining burn dressing materials enabling controlled drug release, iii/ the preparation of polymer ocular insert discs. The surface of polyester vascular prostheses, has been modified by deposition of acrylamide and inducing its polymerization in the solid state by j-radiation. As a result of this treatment, tightness of the prosthesis walls and its surface hydrophilicity have been improved. Toxicological examinations and blood hemolysis studies of modified prostheses showed its good biocompatibility. Various burn dressings have been prepared and the most promising of all investigated turned to be composition consisting of a cotton gauze base and an active polyacrylamide hydrogel layer with addition of glycerin and immobilized Provital /protein preparation/. Preliminary clinical evaluations of this particular dressing showed that the process of burn healing is indeed fast and fully satisfactory. Ocular insert discs made of polymer and containing pilocarpin hydrochloride which is released at controlled rate have been prepared. It has been found that high hydrophilicity and good swelling properties of the ocular insert discs made possible to incorporate pilocarpin hydrochloride into the hydrogel matrix. This work has been carried out under IAEA research contract RB 3379/R-1 POL.

  14. Enteric-coated sustained-release nanoparticles by coaxial electrospray: preparation, characterization, and in vitro evaluation

    Science.gov (United States)

    Hao, Shilei; Wang, Bochu; Wang, Yazhou; Xu, Yingqian

    2014-02-01

    Enteric-coated formulations can delay the release of drugs until they have passed through the stomach. However, high concentration of drugs caused by rapidly released in the small intestine leads to the intestinal damage, and frequent administration would increase the probability of missing medication and reduce the patient compliance. To solve the above-mentioned problems, aspirin-loaded enteric-coated sustained-release nanoparticles with core-shell structure were prepared via one-step method using coaxial electrospray in this study. Eudragit L100-55 as pH-sensitive polymer and Eudragit RS as sustained-release polymer were used for the outer coating and inner core of the nanoparticles, respectively. The maximum loading capacity of nanoparticles was 23.66 % by changing the flow rate ratio of outer/inner solutions, and the entrapment efficiency was nearly 100 %. Nanoparticles with core-shell structure were observed via fluorescence microscope and transmission electron microscope. And pH-sensitive and sustained drug release profiles were observed in the media with different pH values (1.2 and 6.8). In addition, mild cytotoxicity in vitro was detected, and the nanoparticles could be taken up by Caco-2 cells within 1.0 h in cellular uptake study. These results indicate that prepared enteric-coated sustained-release nanoparticles would be a more safety and effective carrier for oral drug delivery.

  15. Storage and sustained release of volatile substances from a hollow silica matrix

    Energy Technology Data Exchange (ETDEWEB)

    Wang Jiexin [Key Lab for Nanomaterials, Ministry of Education, Beijing 100029 (China); Ding Haomin [Research Center of the Ministry of Education for High Gravity Engineering and Technology, Beijing University of Chemical Technology, Beijing 100029 (China); Tao Xia [Key Lab for Nanomaterials, Ministry of Education, Beijing 100029 (China); Chen Jianfeng [Key Lab for Nanomaterials, Ministry of Education, Beijing 100029 (China)

    2007-06-20

    Porous hollow silica nanospheres (PHSNSs) prepared by adopting a nanosized CaCO{sub 3} template were utilized for the first time as a novel carrier for the storage and sustained release of volatile substances. Two types of volatile substances, Indian pipal from perfumes and peroxyacetic acid from disinfectants, were selected and then tested by one simple adsorption process with two separate comparative carriers, i.e. activated carbon and solid porous silica. It was demonstrated that a high storage capacity (9.6 ml{sub perfume}/mg{sub carrier}) of perfume could be achieved in a PHSNS matrix, which was almost 14 times as much as that of activated carbon. The perfume release profiles showed that PHSNSs exhibited sustained multi-stage release behaviour, while the constant release of activated carbon at a low level was discerned. Further, a Higuchi model study proved that the release process of perfume in both carriers followed a Fickian diffusion mechanism. For peroxyacetic acid as a disinfectant model, PHSNSs also displayed a much better delayed-delivery process than a solid porous silica system owing to the existence of unique hollow frameworks. Therefore, the aforementioned excellent sustained-release behaviours would make PHSNSs a promising carrier for storage and sustained delivery applications of volatile substances.

  16. Repeated injections of D-Amphetamine evoke rapid and dynamic changesin phase synchrony between the prefrontal cortex and hippocampus

    Directory of Open Access Journals (Sweden)

    SUNGWOO eAHN

    2013-07-01

    Full Text Available Repeated drug use evokes a number of persistent alterations in oscillatory power and synchrony. How synchronous activity in cortico-hippocampal circuits is progressively modified with repeated drug exposure, however, remains to be characterized. Drugs of abuse induce both short-term and long-term adaptations in cortical and hippocampal circuits and these changes are likely important for the expression of the altered behavioral and neurobiological phenotype associated with addiction. The present study explores how the initial (up to one hour pharmacological response to D-Amphetamine (AMPH is altered with repeated injections in the rat. The methods employed herein allow for the progressive changes in synchronized dynamics with repeated intermittent AMPH exposure to be characterized over short time scales (minutes. Specifically, we examined the temporal variations of phase-locking strength in delta and theta bands within the prefrontal cortex (PFC and between PFC and hippocampus (HC shortly after drug injection. After the first injection of AMPH synchrony increased within the PFC in the delta band, which was followed, by an increase in theta synchrony between the PFC and HC several minutes later. This relationship switched after repeated AMPH injections, where increases in theta synchrony between the PFC and HC preceded increases in delta synchrony in the PFC. The time-course of increases in synchronous activity were negatively correlated between the PFC delta and the PFC-HC theta. Collectively these data highlight the potential role of PFC-HC circuits in the development of addiction and outline dynamic changes in the time-course that cortico-hippocampal circuits become synchronized with repeated AMPH exposure.

  17. The impact of the injection mold temperature upon polymer crystallization and resulting drug release from immediate and sustained release tablets.

    Science.gov (United States)

    Van Renterghem, Jeroen; Dhondt, Heleen; Verstraete, Glenn; De Bruyne, Michiel; Vervaet, Chris; De Beer, Thomas

    2018-01-31

    It was the aim of this study to elucidate the impact of the injection mold temperature upon the polymer crystallinity, its microstructure and the resulting drug release from immediate and sustained release tablets containing semi-crystalline polymers. The immediate release formulation contained 20% (w/w) ketoprofen (KETO) in poly (ethylene oxide) (PEO) and the sustained release formulation contained 20 - 40% (w/w) metoprolol tartrate (MPT) in polycaprolactone (PCL). Physical mixtures of drug-polymer were characterized via isothermal crystallization experiments using DSC and rheological measurements to elucidate the impact of the drug solid-state upon the crystallization kinetics. Tablets were prepared using various thermal histories (extrusion barrel temperature and injection mold temperatures). Polymer crystallinity and microstructure in the tablets was characterized via DSC and polarized optical microscopy. The polymer microstructure was altered by the various applied thermal histories. The differences in PEO crystallinity induced by the various mold temperatures did not affect the KETO dissolution from the tablets. On the other hand, MPT (20 - 40% w/w) dissolution from the PCL matrix when extruded at 80 °C and injection molded at 25 and 35 °C was significantly different due to the changes in the polymer microstructure. More perfect polymer crystals are obtained with higher mold temperatures, decreasing the drug diffusion rate through the PCL matrix. The results presented in this study imply that the injection mold temperature should be carefully controlled for sustained release formulations containing hydrophobic semi-crystalline polymers. Copyright © 2018. Published by Elsevier B.V.

  18. A formulation approach for development of HPMC-based sustained release tablets for tolterodine tartrate with a low release variation

    DEFF Research Database (Denmark)

    Cao, Qing-Ri; Choi, Jae-Seung; Liu, Yan

    2013-01-01

    Objective: The purpose of this study was to develop hydroxypropylmethylcellulose (HPMC)-based sustained release (SR) tablets for tolterodine tartrate with a low drug release variation. Methods: The SR tablets were prepared by formulating a combination of different grades of HPMC as the gelling...... agents. The comparative dissolution study for the HPMC-based SR tablet as a test and Detrusitol(®) SR capsule as a reference was carried out, and the bioequivalence study of the two products was also conducted in human volunteers. Results: The amount of HPMC, the grade of HPMC and the combination ratio...... of different grades of HPMC had remarkable effects on drug release from the SR tablets. Both the test and reference products had no significant difference in terms of comparative dissolution patterns in four different media (f(2) > 50). Furthermore, the dissolution method and rotation speed showed no effects...

  19. Stable and biocompatible genipin-inducing interlayer-crosslinked micelles for sustained drug release

    Energy Technology Data Exchange (ETDEWEB)

    Dai, Yu; Zhang, Xiaojin, E-mail: zhangxj@cug.edu.cn [China University of Geosciences, Faculty of Materials Science and Chemistry (China)

    2017-05-15

    To develop the sustained drug release system, here we describe genipin-inducing interlayer-crosslinked micelles crosslinked via Schiff bases between the amines of amphiphilic linear-hyperbranched polymer poly(ethylene glycol)-branched polyethylenimine-poly(ε-caprolactone) (PEG-PEI-PCL) and genipin. The generation of Schiff bases was confirmed by the color changes and UV-Vis absorption spectra of polymeric micelles after adding genipin. The particle size, morphology, stability, in vitro cytotoxicity, drug loading capacity, and in vitro drug release behavior of crosslinked micelles as well as non-crosslinked micelles were characterized. The results indicated that genipin-inducing interlayer-crosslinked micelles had better stability and biocompatibility than non-crosslinked micelles and glutaraldehyde-inducing interlayer-crosslinked micelles. In addition, genipin-inducing interlayer-crosslinked micelles were able to improve drug loading capacity, reduce the initial burst release, and achieve sustained drug release.

  20. Stable and biocompatible genipin-inducing interlayer-crosslinked micelles for sustained drug release

    Science.gov (United States)

    Dai, Yu; Zhang, Xiaojin

    2017-05-01

    To develop the sustained drug release system, here we describe genipin-inducing interlayer-crosslinked micelles crosslinked via Schiff bases between the amines of amphiphilic linear-hyperbranched polymer poly(ethylene glycol)-branched polyethylenimine-poly( ɛ-caprolactone) (PEG-PEI-PCL) and genipin. The generation of Schiff bases was confirmed by the color changes and UV-Vis absorption spectra of polymeric micelles after adding genipin. The particle size, morphology, stability, in vitro cytotoxicity, drug loading capacity, and in vitro drug release behavior of crosslinked micelles as well as non-crosslinked micelles were characterized. The results indicated that genipin-inducing interlayer-crosslinked micelles had better stability and biocompatibility than non-crosslinked micelles and glutaraldehyde-inducing interlayer-crosslinked micelles. In addition, genipin-inducing interlayer-crosslinked micelles were able to improve drug loading capacity, reduce the initial burst release, and achieve sustained drug release.

  1. Sustained Release of Amoxicillin from Ethyl Cellulose-Coated Amoxicillin/Chitosan–Cyclodextrin-Based Tablets

    OpenAIRE

    Songsurang, Kultida; Pakdeebumrung, Jatuporn; Praphairaksit, Narong; Muangsin, Nongnuj

    2010-01-01

    Sustained release mucoadhesive amoxicillin tablets with tolerance to acid degradation in the stomach were studied. The sustained-release tablets of amoxicillin were prepared from amoxicillin coated with ethyl cellulose (EC) and then formulated into tablets using chitosan (CS) or a mixture of CS and beta-cyclodextrin (CD) as the retard polymer. The effects of various (w/w) ratios of EC/amoxicillin, the particle sized of EC coated amoxicillin and the different (w/w) ratios of CS/CD for the reta...

  2. Pharmacokinetics of propafenone hydrochloride sustained-release capsules in male beagle dogs

    Directory of Open Access Journals (Sweden)

    Liping Pan

    2015-01-01

    Full Text Available This paper describes the development and validation of a liquid chromatography–mass spectrometric assay for propafenone and its application to a pharmacokinetic study of propafenone administered as a new propafenone hydrochloride sustained-release capsule (SR-test, as an instant-release tablet (IR-reference and as the market leader sustained-release capsule (Rythmol, SR-reference in male beagle dogs (n=8. In Study A comparing SR-test with IR-reference in a crossover design Tmax and t1/2 of propafenone for SR-test were significantly higher than those for IR-reference while Cmax and AUC were lower demonstrating the sustained release properties of the new formulation. In Study B comparing SR-test with SR-reference the observed Cmax and AUC of propafenone for SR-test (124.5±140.0 ng/mL and 612.0±699.2 ng·h/mL, respectively were higher than for SR-reference (78.52±72.92 ng/mL and 423.6±431.6 ng·h/mL, respectively although the differences were not significant. Overall, the new formulation has as good if not better sustained release characteristics to the market leader formulation.

  3. Drug Release Characteristics and Tissue Distribution of Rifapentine Polylactic Acid Sustained-Release Microspheres in Rabbits after Paravertebral Implantation.

    Science.gov (United States)

    Zhang, Zheng; Wu, Linbo; Li, Haijian; Long, Zhicheng; Song, Xinghua

    2016-11-01

    Rates of drug-resistant tuberculosis (TB) and TB associated with human immunodeficiency virus (HIV) infection have increased dramatically, intensifying challenges in TB control. New formulations of TB treatment drugs that control drug release and increase local drug concentrations will have a significant impact on mitigating the toxic side effects and increasing the clinical efficacy of anti-TB drugs. The aim was to observe the sustained release characteristics of rifapentine polylactic acid sustained-release microspheres in vivo and the accumulation of rifapentine in other tissues following paravertebral implantation. This study is a basic animal experimental study that began on July 17, 2014 in the Fifth Affiliated hospital of Xinjiang Medical University. One hundred and eight New Zealand white rabbits (weighing 2.8 - 3.0 kg, male and female, China) were randomly divided into three groups of 36 rabbits each. Blood and tissue samples from the liver, lungs, kidneys, vertebrae, and paravertebral muscle were collected at different time points post-surgery. High performance liquid chromatography (HPLC) analysis with a biological internal standard was used to determine the drug concentrations in samples. In group A, no significant differences in rifapentine concentrations in the liver were detected between any two time points (P > 0.05). However, the differences in rifapentine concentrations between day 10 and day 21 were statistically significant (P 0.05). In group B, the differences in rifapentine concentration between days 3 and 10 in vertebral bone and in paravertebral muscles were statistically significant (P polylactic acid sustained-release microspheres, the concentration of rifapentine in local vertebral bone tissues was maintained above the TB minimum inhibitory concentration for up to 60 days with no apparent accumulation of the drug in other tissues.

  4. Enhanced Vascularization in Hybrid PCL/Gelatin Fibrous Scaffolds with Sustained Release of VEGF

    Directory of Open Access Journals (Sweden)

    Kai Wang

    2015-01-01

    Full Text Available Creating a long-lasting and functional vasculature represents one of the most fundamental challenges in tissue engineering. VEGF has been widely accepted as a potent angiogenic factor involved in the early stages of blood vessel formation. In this study, fibrous scaffolds that consist of PCL and gelatin fibers were fabricated. The gelatin fibers were further functionalized by heparin immobilization, which provides binding sites for VEGF and thus enables the sustained release of VEGF. In vitro release test confirms the sustained releasing profile of VEGF, and stable release was observed over a time period of 25 days. In vitro cell assay indicates that VEGF release significantly promoted the proliferation of endothelial cells. More importantly, in vivo subcutaneous implantation reflects that vascularization has been effectively enhanced in the PCL/gelatin scaffolds compared with the PCL counterpart due to the sustained release of VEGF. Therefore, the heparinized PCL/gelatin scaffolds developed in this study may be a promising candidate for regeneration of complex tissues with sufficient vascularization.

  5. Development of lipid micromatrices based sustained release tablets of glipizide: suitability of stearic acid as release retardant

    Directory of Open Access Journals (Sweden)

    Deepak Singh

    2016-06-01

    Full Text Available The objective of research was to explore the suitability of lipids like compritol 888 ATO and stearic acid as release retardant to develop sustained release (SR tablets. The SR micromatrices of lipid (s and glipizide were prepared (LM1- LM6 as intermediate product by fusion method and assessed for various pharmacotechnical properties. Micromatrices were formulated as SR tablets (F1-F6 by direct compression method and subjected to Pharmacopoeial and Non Pharmacopoeial tests.  In vitro drug release behavior of SR tablets demonstrated incomplete release of drug from compitrol based formulations whereas stearic acid based formulations (F4-F6 released more than 90% drug in 12 h with F5 displaying  maximum %CDR of  95.70 ± 0.78%. A t50% of 3 h exhibited by F5 was significantly lower (2.7 h than of marketed formulation (Glytop SR® (t50% = 5.7 h. Similarity and dissimilarity factor for F5, with reference to Glytop SR® was 21.65% and 26.34% respectively, suggesting F5 has potential to exercise better control on drug release. Scanning Electron Microscopy (SEM revealed drug particles embedded in stearic acid micromatrices that were confirmed by The X-ray powder diffraction (XRPD and simultaneously Diffuse Reflectance Infrared Fourier Transform (DRIFT confirmed the stability of F5. Conclusively, stearic acid explored as a suitable lipidic release retardant for development of SR tablet of glipizide that were stable for the test period of 6 months.

  6. Sustained release matrix tablets prepared from cospray dried mixtures with starch hydrophobic esters.

    Science.gov (United States)

    Sakhnini, N; Al-Zoubi, N; Al-Obaidi, G H; Ardakani, A

    2015-03-01

    In this work, starch acetate and propanoate derivatives with moderate degree of substitution were synthesized and characterized for employment as matrix formers for sustained release from tablets. Matrix tablets were prepared from cospray-dried and simple physical mixtures of starch/starch derivatives and theophylline as a model drug. The release was rapid for matrix tablets prepared from simple physical mixtures. On the other hand, tablets prepared from cospray-dried mixtures with starch acetate and starch propanoate showed much slower and extended release. Scanning electron micrographs of tablet surfaces revealed enhanced inter-particulate bonding and plastification for cospray-dried agglomerates in comparison with physical mixtures.

  7. Differential effects of 3,4-methylenedioxypyrovalerone (MDPV) and 4-methylmethcathinone (mephedrone) in rats trained to discriminate MDMA or a d-amphetamine + MDMA mixture.

    Science.gov (United States)

    Harvey, Eric L; Baker, Lisa E

    2016-02-01

    Recent reports on the abuse of novel synthetic cathinone derivatives call attention to serious public health risks of these substances. In response to this concern, a growing body of preclinical research has characterized the psychopharmacology of these substances, particularly mephedrone (MEPH) or methylenedioxypyrovalerone (MDPV), noting their similarities to 3,4-methylenedioxymethamphetamine (MDMA) and cocaine. Few studies have utilized drug discrimination methodology to characterize the psychopharmacological properties of these substances. The present study employed a rodent drug discrimination assay to further characterize the stimulus effects of MEPH and MDPV in comparison to MDMA and to a drug mixture comprised of d-amphetamine and MDMA. Eight male Sprague-Dawley rats were trained to discriminate 1.5 mg/kg MDMA, and eight rats were trained to discriminate a mixture of 1.5 mg/kg MDMA and 0.5 mg/kg d-amphetamine (MDMA + AMPH) from vehicle. Substitution tests were conducted with MDMA, d-amphetamine, MDPV, MEPH, and cocaine. Dose-response curves generated with MDMA and MEPH were comparable between training groups. In contrast, AMPH, MDPV, and cocaine produced only partial substitution in animals trained to discriminate MDMA but produced full substitution in animals trained to discriminate the MDMA + AMPH mixture. These findings indicate that MDPV's effects may be more similar to those of traditional psychostimulants, whereas MEPH exerts stimulus effects more similar to those of MDMA. Additional experiments with selective DA and 5-hydroxytryptamine (5-HT) receptor antagonists are required to further elucidate specific receptor mechanisms mediating the discriminative stimulus effects of MDPV and mephedrone.

  8. Evaluation of selected polysaccharide excipients in buccoadhesive tablets for sustained release of nicotine.

    Science.gov (United States)

    Park, Calum R; Munday, Dale L

    2004-07-01

    Some naturally occurring biocompatible materials were evaluated as mucoadhesive controlled release excipients for buccal drug delivery. A range of tablets were prepared containing 0-50% w/w xanthan gum, karaya gum, guar gum, and glycol chitosan and were tested for swelling, drug release, and mucoadhesion. Guar gum was a poor mucoadhesive and lacked sufficient physical integrity for buccal delivery. Karaya gum demonstrated superior adhesion to guar gum and was able to provide zero-order drug release, but concentrations greater than 50% w/w may be required to provide suitable sustained release. Xanthan gum showed strong adhesion to the mucosal membrane and the 50% w/w formulation produced zero-order drug release over 4 hours, about the normal time interval between daily meals. Glycol chitosan produced the strongest adhesion, but concentrations greater than 50% w/w are required to produce a nonerodible matrix that can control drug release for over 4 hours. Swelling properties of the tablets were found to be a valuable indicator of the ability of the material to produce sustained release. Swelling studies also gave an indication of the adhesion values of the gum material where adhesion was solely dependent upon penetration of the polymer chains into the mucus layer.

  9. Sustained release of complexed DNA from films: Study of bioactivity and intracellular tracking.

    Science.gov (United States)

    Mondal, Debasish; Ramgopal, Yamini; Tiwari, Sandeep Kumar; Venkatraman, Subbu S

    2010-09-01

    Sustained DNA delivery from polymeric films provides a means for localized and prolonged gene therapy. However, in the case of bioactive molecules such as plasmid DNA (pDNA), there are limitations on the achievable release profiles as well as on the maintenance of bioactivity over time. In this report, the authors have investigated the bioactivity of the released DNA (naked and complexed with lipofectamine) from polymeric films using in vitro cell transfection of COS-7 cell lines. The polymeric system consists of a biodegradable semicrystalline polymer such as poly(ε-caprolactone) (PCL) with or without blended gelatin. Sustained release of lipoplexes and of pDNA is shown over several days. However, lipoplexes released from pure PCL films show no transfection on day 18, whereas lipoplexes released from PCL-gelatin films continue to transfect cells on day 18 of release. Confocal studies were used to determine the reasons for this difference in transfection efficiency, and it is proposed that association of the lipoplex with gelatin confers protection from degradation in the cytoplasm. The results also showed that the bioactivity of released lipoplexes was superior to that of the naked pDNA. For both naked pDNA and the lipoplexes, the presence of gelatin helped to maintain the bioactivity over several days.

  10. Preparation of Coated Valproic Acid and Sodium Valproate Sustained-release Matrix Tablets.

    Science.gov (United States)

    Phaechamud, T; Mueannoom, W; Tuntarawongsa, S; Chitrattha, S

    2010-03-01

    The aim of this research was to investigate the technique for preparation of coated valproic acid and sodium valproate sustained-release matrix tablets. Different diluents were tested and selected as the effective absorbent for oily valproic acid. Effect of the amount of absorbent and hydroxypropylmethylcellulose on drug release from valproic acid-sodium valproate matrix tablets prepared with wet granulation technique was evaluated in pH change system. Colloidal silicon dioxide effectively adsorbed liquid valproic acid during wet granulation and granule preparation. The amounts of colloidal silicon dioxide and hydroxypropylmethylcellulose employed in tablet formulations affected drug release from the tablets. The drug release was prominently sustained for over 12 h using hydroxypropylmethylcellulose-based hydrophilic matrix system. The mechanism of drug release through the matrix polymer was a diffusion control. The drug release profile of the developed matrix tablet was similar to Depakine Chrono(®), providing the values of similarity factor (f2) and difference factor (f1) of 85.56 and 2.37, respectively. Eudragit(®) L 30 D-55 was used as effective subcoating material for core matrix tablets before over coating with hydroxypropylmethylcellulose film with organic base solvent. Drug release profile of coated matrix tablet was almost similar to that of Depakine Chrono(®).

  11. Sustained Release of BMP-2 in Bioprinted Alginate for Osteogenicity in Mice and Rats

    Science.gov (United States)

    Poldervaart, Michelle T.; Wang, Huanan; van der Stok, Johan; Weinans, Harrie; Leeuwenburgh, Sander C. G.; Öner, F. Cumhur; Dhert, Wouter J. A.; Alblas, Jacqueline

    2013-01-01

    The design of bioactive three-dimensional (3D) scaffolds is a major focus in bone tissue engineering. Incorporation of growth factors into bioprinted scaffolds offers many new possibilities regarding both biological and architectural properties of the scaffolds. This study investigates whether the sustained release of bone morphogenetic protein 2 (BMP-2) influences osteogenicity of tissue engineered bioprinted constructs. BMP-2 loaded on gelatin microparticles (GMPs) was used as a sustained release system, which was dispersed in hydrogel-based constructs and compared to direct inclusion of BMP-2 in alginate or control GMPs. The constructs were supplemented with goat multipotent stromal cells (gMSCs) and biphasic calcium phosphate to study osteogenic differentiation and bone formation respectively. BMP-2 release kinetics and bioactivity showed continuous release for three weeks coinciding with osteogenicity. Osteogenic differentiation and bone formation of bioprinted GMP containing constructs were investigated after subcutaneous implantation in mice or rats. BMP-2 significantly increased bone formation, which was not influenced by the release timing. We showed that 3D printing of controlled release particles is feasible and that the released BMP-2 directs osteogenic differentiation in vitro and in vivo. PMID:23977328

  12. Sustained release of BMP-2 in bioprinted alginate for osteogenicity in mice and rats.

    Directory of Open Access Journals (Sweden)

    Michelle T Poldervaart

    Full Text Available The design of bioactive three-dimensional (3D scaffolds is a major focus in bone tissue engineering. Incorporation of growth factors into bioprinted scaffolds offers many new possibilities regarding both biological and architectural properties of the scaffolds. This study investigates whether the sustained release of bone morphogenetic protein 2 (BMP-2 influences osteogenicity of tissue engineered bioprinted constructs. BMP-2 loaded on gelatin microparticles (GMPs was used as a sustained release system, which was dispersed in hydrogel-based constructs and compared to direct inclusion of BMP-2 in alginate or control GMPs. The constructs were supplemented with goat multipotent stromal cells (gMSCs and biphasic calcium phosphate to study osteogenic differentiation and bone formation respectively. BMP-2 release kinetics and bioactivity showed continuous release for three weeks coinciding with osteogenicity. Osteogenic differentiation and bone formation of bioprinted GMP containing constructs were investigated after subcutaneous implantation in mice or rats. BMP-2 significantly increased bone formation, which was not influenced by the release timing. We showed that 3D printing of controlled release particles is feasible and that the released BMP-2 directs osteogenic differentiation in vitro and in vivo.

  13. Polymer excipients enable sustained drug release in low pH from mechanically strong inorganic geopolymers.

    Science.gov (United States)

    Jämstorp, Erik; Yarra, Tejaswi; Cai, Bing; Engqvist, Håkan; Bredenberg, Susanne; Strømme, Maria

    2012-01-01

    Improving acid resistance, while maintaining the excellent mechanical stability is crucial in the development of a sustained and safe oral geopolymer dosage form for highly potent opioids. In the present work, commercially available Methacrylic acid-ethyl acrylate copolymer, Polyethylene-glycol (PEG) and Alginate polymer excipients were included in dissolved or powder form in geopolymer pellets to improve the release properties of Zolpidem, herein acting as a model drug for the highly potent opioid Fentanyl. Scanning electron microscopy, compression strength tests and drug release experiments, in gastric pH 1 and intestinal pH 6.8 conditions, were performed. The polymer excipients, with an exception for PEG, reduced the drug release rate in pH 1 due to their ability to keep the pellets in shape, in combination with the introduction of an insoluble excipient, and thereby maintain a barrier towards drug diffusion and release. Neither geopolymer compression strength nor the release in pH 6.8 was considerably impaired by the incorporation of the polymer excipients. The geopolymer/polymer composites combine high mechanical strength and good release properties under both gastric and intestinal pH conditions, and are therefore promising oral dosage forms for sustained release of highly potent opioids.

  14. Formulation and In vitro/In vivo Evaluation of Sustained Release ...

    African Journals Online (AJOL)

    Purpose: To develop and optimise sustained release (SR) matrix tablets of diltiazem hydrochloride (DHL). Methods: DHL tablets were prepared by direct compression and consisted of hydroxyprpoylmethyl cellulose, Kollidon SR and Eudragit RSPO. A 32 full factorial design was applied to study the effect of polymers used ...

  15. Formulation and In vitro/In vivo Evaluation of Sustained Release ...

    African Journals Online (AJOL)

    HP

    2013-07-15

    Jul 15, 2013 ... Purpose: To develop and optimise sustained release (SR) matrix tablets of diltiazem hydrochloride (DHL). Methods: DHL tablets were prepared by direct compression and consisted of hydroxyprpoylmethyl cellulose,. Kollidon SR and Eudragit RSPO. A 32 full factorial design was applied to study the effect of ...

  16. Formulation and evaluation of sustained release enteric-coated pellets of budesonide for intestinal delivery.

    Science.gov (United States)

    Raval, Mihir K; Ramani, Riddhi V; Sheth, Navin R

    2013-10-01

    The aim of present work was to develop intestinal-targeted pellets of Budesonide, a potent glucocorticoid, used for the treatment of ulcerative colitis and Crohn's disease by extrusion and spheronization method. Current available oral formulations of Budesonide have low efficacy because of the premature drug release in the upper part of the gastrointestinal tract. In this study, a pH-controlled intestinal-targeted pellet of budesonide was established using 3(2) full factorial design by giving an enteric coating with Eudragit S100. Budesonide-sustained release pellets were prepared by extruder and spheronization technique using a combination of water-soluble and permeable polymers by applying 3(2) full factorial design. The pellets were coated by spray coating technique using Eudragit S100 as an enteric polymer. The pellets were characterized for its flowability, sphericity, friability, and in vitro drug release. Release behaviour was studied in different pH media. The release profile was studied for the mechanism of drug release. The optimized formulation showed negligible drug release in the stomach followed by release for 12 h in the intestinal pH. Differential scanning calorimetry and Fourier Transform Infrared Spectroscopy studies indicated no interaction between drug and polymer. Scanning Electron Microscopy image of coated pellets suggested a uniform and smooth coat over the surface of pellets. Accelerated stability studies showed a stable nature of drug in the formulation. All evaluation parameter showed that pellets were good in spherocity and flowability. Sustained release pellets of Budesonide could be prepared by extrusion and spheronization which released the drug in intestinal pH for an intestine to treat inflammatory bowel disease. A ratio of polymer combination could be decided using a full factorial design.

  17. Sustained-release of caffeine from a polymeric tablet matrix: An in vitro and pharmacokinetic study

    Energy Technology Data Exchange (ETDEWEB)

    Tan, Donna [Defence Medical and Environmental Research Institute, DSO National Laboratories (Kent Ridge), 27 Medical Drive, 12-00, Singapore 117597 (Singapore); Zhao Bin [Defence Medical and Environmental Research Institute, DSO National Laboratories (Kent Ridge), 27 Medical Drive, 12-00, Singapore 117597 (Singapore); Moochhala, Shabbir [Defence Medical and Environmental Research Institute, DSO National Laboratories (Kent Ridge), 27 Medical Drive, 12-00, Singapore 117597 (Singapore)]. E-mail: mshabbir@dso.org.sg; Yang Yiyan [Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, 04-01, The Nanos, Singapore 138669 (Singapore)

    2006-07-25

    Caffeine is utilized as a stimulant to impart a desired level of alertness during certain working hours. Usually, a single dose of caffeine induces 2-3 h of alertness coupled with side effects whereas a longer effect of 8-12 h is very useful for both daily life and military action. Thus, there is a need to deliver the stimulant continuously to an individual at one time to impart an increased level of alertness for the period stated after administration. This study aimed to design a polymeric microparticle system for sustained delivery of caffeine using a polymeric matrix. Poly(ethylene oxide) (PEO) was used as the erodible matrix material and the caffeine polymeric tablets were fabricated by compression using a Graseby Specac hydraulic press. In vitro release profiles as well as the pharmacokinetics studies data were obtained. Caffeine tablets fabricated using various polymers showed a high initial burst release type profile as compared to the caffeine-PEO-tablet. The PK studies showed sustained delivery of caffeine resulted in two expected phenomena: a reduction in the initial high rate of caffeine release (burst release) as well as a reduction in the change in caffeine concentration in the systemic circulation. A simple two-component system for sustained-release caffeine formulation therefore has been achieved.

  18. Floating solid cellulose nanofibre nanofoams for sustained release of the poorly soluble model drug furosemide

    DEFF Research Database (Denmark)

    Svagan, Anna Justina; Müllertz, Anette; Löbmann, Korbinian

    2017-01-01

    OBJECTIVES: This study aimed to prepare a furosemide-loaded sustained release cellulose nanofibre (CNF)-based nanofoams with buoyancy. METHODS: Dry foams consisting of CNF and the model drug furosemide at concentrations of 21% and 50% (w/w) have been prepared by simply foaming a CNF-drug suspension...... followed by drying. The resulting foams were characterized towards their morphology, solid state properties and dissolution kinetics. KEY FINDINGS: Solid state analysis of the resulting drug-loaded foams revealed that the drug was present as an amorphous sodium furosemide salt and in form of furosemide...... form I crystals embedded in the CNF foam cell walls. The foams could easily be shaped and were flexible, and during the drug release study, the foam pieces remained intact and were floating on the surface due to their positive buoyancy. Both foams showed a sustained furosemide release compared...

  19. [Application of an artificial neural network in the design of sustained-release dosage forms].

    Science.gov (United States)

    Wei, X H; Wu, J J; Liang, W Q

    2001-09-01

    To use the artificial neural network (ANN) in Matlab 5.1 tool-boxes to predict the formulations of sustained-release tablets. The solubilities of nine drugs and various ratios of HPMC: Dextrin for 63 tablet formulations were used as the ANN model input, and in vitro accumulation released at 6 sampling times were used as output. The ANN model was constructed by selecting the optimal number of iterations (25) and model structure in which there are one hidden layer and five hidden layer nodes. The optimized ANN model was used for prediction of formulation based on desired target in vitro dissolution-time profiles. ANN predicted profiles based on ANN predicted formulations were closely similar to the target profiles. The ANN could be used for predicting the dissolution profiles of sustained release dosage form and for the design of optimal formulation.

  20. Continuous melt granulation to develop high drug loaded sustained release tablet of Metformin HCl

    Directory of Open Access Journals (Sweden)

    Pradnya Vaingankar

    2017-01-01

    The developed matrix tablet (75% drug loading resulted in 670 mg of weight for 500 mg dose strength and showed sustained drug release over 10 h. When compared, with conventional granulation techniques, it was observed that, under identical compression force, the tablet prepared by MG exhibited superior compactibility along with tablet hardness and optimal drug release profile. FTIR suggested nonexistence of chemical interaction between the drug and the other excipients while XRD and DSC analysis revealed the crystalline state of the drug. Furthermore, the results obtained from Raman spectroscopy proved the uniform distribution of the Metformin HCl and polymer in the final dosage form. This technology leads to the manufacture of sustained release matrix formulation with reduced tablet size of a high dose, highly water soluble drug otherwise difficult to process using standard batch-granulation.

  1. Preparation and characterization of anti-algal sustained-release granules and their inhibitory effects on algae.

    Science.gov (United States)

    Ni, Lixiao; Acharya, Kumud; Ren, Gaoxiang; Li, Shiyin; Li, Yiping; Li, Yong

    2013-04-01

    The objectives of this work were to prepare and characterize an anti-algal sustained-release granule, then study its mode of action on Microcystis aeruginosa. The anti-algal sustained-release granule was prepared with artemisinin using alginate-chitosan microcapsule technology and characterized by a high performance liquid chromatography with an evaporative light-scattering detector, Fourier transform infrared spectral analysis, and a scanning electron microscope. The optimum preparation (in %, w/v) using the orthogonal method was: 2.5 sodium alginate; 0.25 chloride; 0.6 artemisinin; 2 calcium chloride; and 1.5 mL of the cross-linking agent, glutaraldehyde. These artemisinin sustained-release granules had a high encapsulation efficiency (up to 68%) and good release properties (release time of more than 40 d). Artemisinin sustained-release granules released cumulatively in a solution containing M. aeruginosa, and the stress on algae increased gradually within 30 d. Artemisinin sustained-release granules decreased the content of the soluble protein, Chlorophyll a in 30 d, increased the superoxide dismutase activity of M. aeruginosa, but exerted no effect on the soluble sugar content. Compared to direct dosing of artemisinin, algae can be inhibited longer and more effectively by the artemisinin sustained-release granules. The results of our research can aid in the development of new anti-algal sustained-release granules and lead to further study of their application in the field. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. Formulation and in vitro, in vivo evaluation of effervescent floating sustained-release imatinib mesylate tablet.

    Directory of Open Access Journals (Sweden)

    Ali Kadivar

    Full Text Available Imatinib mesylate is an antineoplastic agent which has high absorption in the upper part of the gastrointestinal tract (GIT. Conventional imatinib mesylate (Gleevec tablets produce rapid and relatively high peak blood levels and requires frequent administration to keep the plasma drug level at an effective range. This might cause side effects, reduced effectiveness and poor therapeutic management. Therefore, floating sustained-release Imatinib tablets were developed to allow the tablets to be released in the upper part of the GIT and overcome the inadequacy of conventional tablets.Floating sustained-release Imatinib mesylate tablets were prepared using the wet granulation method. Tablets were formulated using Hydroxypropyl Methylcellulose (HPMC K4M, with Sodium alginate (SA and Carbomer 934P (CP as release-retarding polymers, sodium bicarbonate (NaHCO3 as the effervescent agent and lactose as a filler. Floating behavior, in vitro drug release, and swelling index studies were conducted. Initial and total drug release duration was compared with a commercial tablet (Gleevec in 0.1 N HCl (pH 1.2 at 37 ± 0.5°C for 24 hours. Tablets were then evaluated for various physical parameters, including weight variation, thickness, hardness, friability, and drug content. Consequently, 6 months of physical stability studies and in vitro gastro-retentive studies were conducted.Statistical data analysis revealed that tablets containing a composition of 14.67% w/w HPMC K4M, 10.67%, w/w Na alginate, 1.33%, w/w Carbomer 934P and 9.33%, w/w NaHCO3 produced the most favorable formulation to develop 24-hour sustained-release tablets with optimum floating behavior and satisfactory physicochemical characteristics. Furthermore, in vitro release study revealed that the formulated SR tablet had significantly lower Cmax and higher Tmax compared to the conventional tablet (Gleevec. Thus, formulated SR tablets preserved persistent concentration of plasma up to 24 hours

  3. Formulation and in vitro, in vivo evaluation of effervescent floating sustained-release imatinib mesylate tablet.

    Science.gov (United States)

    Kadivar, Ali; Kamalidehghan, Behnam; Javar, Hamid Akbari; Davoudi, Ehsan Taghizadeh; Zaharuddin, Nurul Dhania; Sabeti, Bahareh; Chung, Lip Yong; Noordin, Mohamed Ibrahim

    2015-01-01

    Imatinib mesylate is an antineoplastic agent which has high absorption in the upper part of the gastrointestinal tract (GIT). Conventional imatinib mesylate (Gleevec) tablets produce rapid and relatively high peak blood levels and requires frequent administration to keep the plasma drug level at an effective range. This might cause side effects, reduced effectiveness and poor therapeutic management. Therefore, floating sustained-release Imatinib tablets were developed to allow the tablets to be released in the upper part of the GIT and overcome the inadequacy of conventional tablets. Floating sustained-release Imatinib mesylate tablets were prepared using the wet granulation method. Tablets were formulated using Hydroxypropyl Methylcellulose (HPMC K4M), with Sodium alginate (SA) and Carbomer 934P (CP) as release-retarding polymers, sodium bicarbonate (NaHCO3) as the effervescent agent and lactose as a filler. Floating behavior, in vitro drug release, and swelling index studies were conducted. Initial and total drug release duration was compared with a commercial tablet (Gleevec) in 0.1 N HCl (pH 1.2) at 37 ± 0.5°C for 24 hours. Tablets were then evaluated for various physical parameters, including weight variation, thickness, hardness, friability, and drug content. Consequently, 6 months of physical stability studies and in vitro gastro-retentive studies were conducted. Statistical data analysis revealed that tablets containing a composition of 14.67% w/w HPMC K4M, 10.67%, w/w Na alginate, 1.33%, w/w Carbomer 934P and 9.33%, w/w NaHCO3 produced the most favorable formulation to develop 24-hour sustained-release tablets with optimum floating behavior and satisfactory physicochemical characteristics. Furthermore, in vitro release study revealed that the formulated SR tablet had significantly lower Cmax and higher Tmax compared to the conventional tablet (Gleevec). Thus, formulated SR tablets preserved persistent concentration of plasma up to 24 hours. In conclusion

  4. Sustained protein release from hydrogel microparticles using layer-by-layer (LbL) technology.

    Science.gov (United States)

    Sakr, Omar S; Jordan, Olivier; Borchard, Gerrit

    2016-10-01

    Since most of developed therapeutic proteins are intended to treat chronic diseases, patients are prescribed multiple injections for long time periods, and therefore, sustained release formulations are much needed. However, challenges facing these formulations are quite significant. In this context, a model protein, lysozyme (Lys), was loaded on hydrogel microparticles (beads) and the ability of layer-by-layer (LbL) coating to control Lys release and maintain its activity over a one-month period was investigated. LbL coating was composed of chondroitin sulfate as a negatively charged polyelectrolyte and a biocompatible, hydrolytically degradable poly β-aminoester as a positively charged polyelectrolyte. Loading distribution was monitored by fluorescence imaging, and followed by depositing a series of LbL coatings of different thicknesses. Release of Lys from these formulations was studied and activity of released fraction was determined. Lys was loaded effectively on hydrogel beads achieving about 9 mg protein/100 mg wet spheres. LbL coating was proven successful by monitoring the zeta potential of the beads, which was reversed after the addition of each layer. In vitro release studies showed sustained release profiles that depend on the thickness of the deposited coat, with t50 extended from 4.9 to 143.9 h. More importantly, released Lys possessed a high degree of biological activity during the course of release maintaining at least 72% of initial activity. Successful loading of Lys and extension of its release while maintaining a considerable degree of activity might make this formulation suitable for use with other active therapeutic proteins.

  5. PNIPAAM modified mesoporous hydroxyapatite for sustained osteogenic drug release and promoting cell attachment

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Tao [The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, 237 Luoyu Road, Wuhan 430079 (China); Tan, Lei [Key Laboratory of Biomedical Polymers of Ministry of Education, College of Chemistry and Molecular Science, Wuhan University, Wuhan 430072 (China); Cheng, Ning; Yan, Qi; Zhang, Yu-Feng [The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, 237 Luoyu Road, Wuhan 430079 (China); Liu, Chuan-Jun, E-mail: cjliu@whu.edu.cn [Key Laboratory of Biomedical Polymers of Ministry of Education, College of Chemistry and Molecular Science, Wuhan University, Wuhan 430072 (China); Shi, Bin, E-mail: shibin_dentist@126.com [The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, 237 Luoyu Road, Wuhan 430079 (China)

    2016-05-01

    This work presented a sustained release system of simvastatin (SIM) based on the mesoporous hydroxyapatite (MHA) capped with poly(N-isopropylacrylamide) (PNIPAAM). The MHA was prepared by using cetyltrimethylammonium bromide (CTAB) as a template and the modified PNIPAAM layer on the surface of MHA was fabricated through surface-initiated atom transfer radical polymerization (SI-ATRP). The SIM loaded MHA-PNIPAAM showed a sustained release of SIM at 37 °C over 16 days. The bone marrow mesenchymal stem cell (BMSC) proliferation was assessed by cell counting kit-8 (CCK-8) assay, and the osteogenic differentiation was evaluated by alkaline phosphatase (ALP) activity and Alizarin Red staining. The release profile showed that the release of SIM from MHA-SIM-PNIPAAM lasted 16 days and the cumulative amount of released SIM was almost seven-fold than MHA-SIM. Besides, SIM loaded MHA-PNIPAAM exhibited better performance on cell proliferation, ALP activity, and calcium deposition than pure MHA due to the sustained release of SIM. The quantity of ALP in MHA-SIM-PNIPAAM group was more than two fold than pure MHA group at 7 days. Compared to pure MHA, better BMSC attachment on PNIPAAM modified MHA was observed using fluorescent microscopy, indicating the better biocompatibility of MHA-PNIPAAM. - Highlights: • PNIPAAM modified mesoporous hydroxyapatite (MHA) was fabricated by SI-ATRP. • SIM loaded MHA-PNIPAAM continually released SIM in effect concentration for 16 days. • MHA-SIM-PNIPAAM behaved well on cell proliferation, ALP activity and calcium deposition.

  6. Taste masking of ofloxacin and formation of interpenetrating polymer network beads for sustained release

    Directory of Open Access Journals (Sweden)

    A. Michael Rajesh

    2017-08-01

    Full Text Available The objective of this study was to carry out taste masking of ofloxacin (Ofl by ion exchange resins (IERs followed by sustained release of Ofl by forming interpenetrating polymer network (IPN beads. Drug-resin complexes (DRCs with three different ratios of Ofl to IERs (1:1, 1:2, 1:4 were prepared by batch method and investigated for in vivo and in vitro taste masking. DRC of methacrylic acid-divinyl benzene (MD resin and Ofl prepared at a ratio of 1:4 was used to form IPN beads. IPN beads of MD 1:4 were prepared by following the ionic cross-linking method using sodium carboxymethyl xanthan gum (SCMXG and SCMXG-sodium carboxymethyl cellulose (SCMXG-SCMC. IPN beads were characterized with FT-IR and further studied on sustained release of Ofl at different pH. In vivo taste masking carried out by human volunteers showed that MD 1:4 significantly reduced the bitterness of Ofl. Characterization studies such as FT-IR, DSC, P-XRD and taste masking showed that complex formation took place between drug and resin. In vitro study at gastric pH showed complete release of drug from MD 1:4 within 30 min whereas IPN beads took 5 h at gastric pH and 10 h at salivary pH for the complete release of drug. As the crosslinking increased the release kinetics changed into non-Fickian diffusion to zero-order release mechanism. MD 1:4 showed better performance for the taste masking of Ofl and IPNs beads prepared from it were found useful for the sustained release of Ofl at both the pH, indicating a versatile drug delivery system.

  7. Development and evaluation of Ketoprofen sustained release matrix tablet using Hibiscus rosa-sinensis leaves mucilage

    Directory of Open Access Journals (Sweden)

    M. Kaleemullah

    2017-07-01

    Full Text Available Currently, the use of natural gums and mucilage is of increasing importance in pharmaceutical formulations as valuable drug excipient. Natural plant-based materials are economic, free of side effects, biocompatible and biodegradable. Therefore, Ketoprofen matrix tablets were formulated by employing Hibiscus rosa-sinensis leaves mucilage as natural polymer and HPMC (K100M as a synthetic polymer to sustain the drug release from matrix system. Direct compression method was used to develop sustained released matrix tablets. The formulated matrix tablets were evaluated in terms of physical appearance, weight variation, thickness, diameter, hardness, friability and in vitro drug release. The difference between the natural and synthetic polymers was investigated concurrently. Matrix tablets developed from each formulation passed all standard physical evaluation tests. The dissolution studies of formulated tablets revealed sustained drug release up to 24 h compared to the reference drug Apo Keto® SR tablets. The dissolution data later were fitted into kinetic models such as zero order equation, first order equation, Higuchi equation, Hixson Crowell equation and Korsmeyer-Peppas equation to study the release of drugs from each formulation. The best formulations were selected based on the similarity factor (f2 value of 50% and more. Through the research, it is found that by increasing the polymers concentration, the rate of drug release decreased for both natural and synthetic polymers. The best formulation was found to be F3 which contained 40% Hibiscus rosa-sinensis mucilage polymer and showed comparable dissolution profile to the reference drug with f2 value of 78.03%. The release kinetics of this formulation has shown to follow non-Fickian type which involved both diffusion and erosion mechanism. Additionally, the statistical results indicated that there was no significant difference (p > 0.05 between the F3 and reference drug in terms of MDT and

  8. Compression of coated drug beads for sustained release tablet of glipizide: formulation, and dissolution.

    Science.gov (United States)

    Nguyen, Chien; Christensen, J Mark; Ayres, James W

    2014-02-01

    A promising glipizide formulation comprising compression of four-layer coated beads into tablets was prepared. The tablet offered the advantages of: a two-hour lag time before drug release, retaining sustained release characteristics and providing approximately zero-order drug release. Drug release was nearly independent of paddle speeds of 50 and 100 rpm releasing 80% over 14 h similar to the commercial glipizide osmotic pump tablet during dissolution testing while keeping the benefits of multiparticular dosage forms. The tablets contain beads with four layers: (1) the innermost layer consists of 2.5 g glipizide and 3.75 g solid ethylcellulose (Surelease®) coated onto 71.25 g of sugar beads; (2) next a hardening layer of 5 g of hypromellose; (3) the controlled release layer of 7.5 g of Surelease®:lactose at a solids ratio of 100:7 and (4) an outermost layer of 20 g of lactose:sodium starch glycolate (Explotab®) at a 2:1 ratio. Then, beads were compressed into tablets containing 11 mg of glipizide using 1500 lbs of compression pressure. The dissolution test similarity factor (f2) was above 50 for all test conditions for formulation F13 and Glucotrol® with a high of 69.9. The two Surelease® layers both aid controlling drug release, with the Surelease®-drug layer affecting drug release to a greater extent.

  9. Postoperative Analgesia Due to Sustained-Release Buprenorphine, Sustained-Release Meloxicam, and Carprofen Gel in a Model of Incisional Pain in Rats (Rattus norvegicus).

    Science.gov (United States)

    Seymour, Travis L; Adams, Sean C; Felt, Stephen A; Jampachaisri, Katechan; Yeomans, David C; Pacharinsak, Cholawat

    2016-01-01

    Postoperative analgesia in laboratory rats is complicated by the frequent handling associated with common analgesic dosing requirements. Here, we evaluated sustained-release buprenorphine (Bup-SR), sustained-release meloxicam (Melox-SR), and carprofen gel (CG) as refinements for postoperative analgesia. The aim of this study was to investigate whether postoperative administration of Bup-SR, Melox-SR, or CG effectively controls behavioral mechanical and thermal hypersensitivity in a rat model of incisional pain. Rats were randomly assigned to 1 of 5 treatment groups: saline, 1 mL/kg SC BID; buprenorphine HCl (Bup HCl), 0.05 mg/kg SC BID; Bup-SR, 1.2 mg/kg SC once; Melox-SR, 4 mg/kg SC once; and CG, 2 oz PO daily. Mechanical and thermal hypersensitivity were tested daily from day-1 through 4. Bup HCl and Bup-SR attenuated mechanical and thermal hypersensitivity on days 1 through 4. Melox-SR and CG attenuated mechanical hypersensitivity-but not thermal hypersensitivity-on days 1 through 4. Plasma concentrations, measured by using UPLC with mass spectrometry, were consistent between both buprenorphine formulations. Gross pathologic examination revealed no signs of toxicity in any group. These findings suggest that postoperative administration of Bup HCl and Bup-SR-but not Melox-SR or CG-effectively attenuates mechanical and thermal hypersensitivity in a rat model of incisional pain.

  10. Cyclodextrin-containing hydrogels as an intraocular lens for sustained drug release

    Science.gov (United States)

    Li, Xiao; Zhao, Yang; Wang, Kaijie; Yang, Xiaohui; Zhu, Siquan

    2017-01-01

    To improve the efficacy of anti-inflammatory factors in patients who undergo cataract surgery, poly(2-hydroxyethyl methacrylate-co-methyl methacrylate) (p(HEMA-co-MMA)) hydrogels containing β-cyclodextrin (β-CD) (pHEMA/MMA/β-CD) were designed and prepared as intraocular lens (IOLs) biomaterials that could be loaded with and achieve the sustained release of dexamethasone. A series of pHEMA/MMA/β-CD copolymers containing different ratios of β-CD (range, 2.77 to 10.24 wt.%) were obtained using thermal polymerization. The polymers had high transmittance at visible wavelengths and good biocompatibility with mouse connective tissue fibroblasts. Drug loading and release studies demonstrated that introducing β-CD into hydrogels increased loading efficiency and achieved the sustained release of the drug. Administering β-CD via hydrogels increased the equilibrium swelling ratio, elastic modulus and tensile strength. In addition, β-CD increased the hydrophilicity of the hydrogels, resulting in a lower water contact angle and higher cellular adhesion to the hydrogels. In summary, pHEMA/MMA/β-CD hydrogels show great potential as IOL biomaterials that are capable of maintaining the sustained release of anti-inflammatory drugs after cataract surgery. PMID:29244868

  11. Coaxial Electrospray of Ranibizumab-Loaded Microparticles for Sustained Release of Anti-VEGF Therapies.

    Directory of Open Access Journals (Sweden)

    Leilei Zhang

    Full Text Available Age-related macular degeneration (AMD is the leading cause of vision loss and blindness in people over age 65 in industrialized nations. Intravitreous injection of anti-VEGF (vascular endothelial growth factor therapies, such as ranibizumab (trade name: Lucentis, provides an effective treatment option for neovascular AMD. We have developed an improved coaxial electrospray (CES process to encapsulate ranibizumab in poly(lactic-co-glycolic acid (PLGA microparticles (MPs for intravitreous injection and sustained drug release. This microencapsulation process is advantageous for maintaining the stability of the coaxial cone-jet configurations and producing drug-loaded MPs with as high as 70% encapsulation rate and minimal loss of bioactivitiy. The utility of this emerging process in intravitreous drug delivery has been demonstrated in both benchtop and in vivo experiments. The benchtop test simulates ocular drug release using PLGA MPs encapsulating a model drug. The in vivo experiment evaluates the inflammation and retinal cell death after intravitreal injection of the MPs in a chick model. The experimental results show that the drug-load MPs are able to facilitate sustained drug release for longer than one month. No significant long term microglia reaction or cell death is observed after intravitreal injection of 200 μg MPs. The present study demonstrates the technical feasibility of using the improved CES process to encapsulate water-soluble drugs at a high concentration for sustained release of anti-VEGF therapy.

  12. Relationship between drug discrimination and ratings of subjective effects: implications for assessing and understanding the abuse potential of D-amphetamine in humans.

    Science.gov (United States)

    Reynolds, Anna R; Bolin, B Levi; Stoops, William W; Rush, Craig R

    2013-09-01

    The discriminative and subjective effects of drugs in humans are related, but the full extent of this relationship remains to be determined. To further explore this relationship, a retrospective analysis was conducted on data from six studies completed in our laboratory that used identical procedures. The relationship between the discriminative and subjective effects of a range of doses of D-amphetamine (i.e. 2.5-15 mg) was examined using correlational analyses. Significant correlations with discrimination performance were observed on 15 of 20 items from the Drug-Effect Questionnaire across a range of qualities [e.g. Pay For (a positive effect indicative of abuse potential) and Active (a stimulant-like effect)], but the magnitude of these relationships was modest (reffects contribute to the discriminative effects of D-amphetamine and indicate that the former are a more practical means to assess the abuse potential of drugs. Although these procedures are fundamentally related in that they rely on the presence of an interoceptive drug state, they differ in the dimension(s) of the interoceptive effects that participants must quantify. The simultaneous use of drug discrimination and subjective effects may, therefore, reveal complimentary aspects of drug effects that underlie their potential for abuse.

  13. Effects of atomoxetine, desipramine, d-amphetamine and methylphenidate on impulsivity in juvenile rats, measured in a T-maze procedure.

    Science.gov (United States)

    Bizot, Jean-Charles; David, Sabrina; Trovero, Fabrice

    2011-02-01

    Impulsivity is a core symptom of Attention Deficit/Hyperactivity Disorder (ADHD). In the present study, we assessed the effects of two stimulants, methylphenidate and d-amphetamine and of two non stimulant noradrenaline reuptake inhibitors, atomoxetine and desipramine, on the tolerance to delay of reward, taken as an index of impulsivity, in juvenile Wistar rats. Animals were trained in a T-maze to choose between a small-and-immediate reward and a large-but-30s-delayed reward. The effects of drugs were studied on the performance of animals at 30-40 day of age. Methylphenidate (3mg/kg), atomoxetine (1mg/kg), d-amphetamine (1 and 2mg/kg) and desipramine (8 and 16mg/kg) increased the number of choices of the large-but-delayed reward, i.e. decreased impulsivity. Given that these drugs are commonly prescribed in ADHD, these data indicate that the T-maze procedure in juvenile animals may be suitable for testing the therapeutic potential of drugs intended to the treatment of ADHD in children. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  14. Sustained release of estrogens from PEGylated nanoparticles for treatment of secondary spinal cord injury

    Science.gov (United States)

    Barry, John

    Spinal Cord Injury (SCI) is a debilitating condition which causes neurological damage and can result in paralysis. SCI results in immediate mechanical damage to the spinal cord, but secondary injuries due to inflammation, oxidative damage, and activated biochemical pathways leading to apoptosis exacerbate the injury. The only currently available treatment, methylprednisolone, is controversial because there is no convincing data to support its therapeutic efficacy for SCI treatment. In the absence of an effective SCI treatment option, 17beta-estradiol has gained significant attention for its anti-oxidant, anti-inflammatory, and anti-apoptotic abilities, all events associated with secondary. Sadly, 17beta-estradiol is associated with systemic adverse effects preclude the use of free estrogen even for local administration due to short drug half-life in the body. Biodegradable nanoparticles can be used to increase half-life after local administration and to bestow sustained release. Sustained release using PEGylated biodegradable polymeric nanoparticles constructed from poly(lactic-co-glycolic acid) (PLGA) will endow a consistent, low, but effective dose to be delivered locally. This will limit systemic effects due to local administration and low dose, sustained release. PLGA was chosen because it has been used extensively for sustained release, and has a record of safety in humans. Here, we show the in vitro efficacy of PEGylated nanoparticles loaded with 17beta-estradiol for treatment of secondary SCI. We achieved a high loading efficiency and controlled release from the particles over a several day therapeutic window. The particles also show neuroprotection in two in vitro cell culture models. Both the dose and pretreatment time with nanoparticles was evaluated in an effort to translate the treatment into an animal model for further study.

  15. Sustained release of diclofenac from polymer-containing suppository and the mechanism involved.

    Science.gov (United States)

    Azechi, Y; Ishikawa, K; Mizuno, N; Takahashi, K

    2000-11-01

    Sustained release of diclofenac sodium (DcNa) from suppositories composed of triglycerides and polymer was investigated by dissolution testing through an artificial membrane. DcNa was slowly released from a suppository containing carboxyvinyl polymer (CVP), and the extent of the release decreased with the amount of CVP added. Little effect was noted with the addition of other water-soluble polymers, such as hydroxyethylcellulose (HEC), xanthan gum, and polyvinylalcohol (PVA). When sodium benzoate was used instead of DcNa, a similar result was obtained with the addition of CVP. The result of release rate analysis together with the viscosity and pH in these cases showed that the reduction of solubility and diffusion due to sodium exchange between DcNa and CVP played an important role in the sustained release from the suppository. Also, in comparison with the results when CVP was not used, the plasma concentration profile of diclofenac after the administration of CVP suppository displayed a twofold longer half-life time.

  16. Sustained-releasing hollow microparticles with dual-anticancer drugs elicit greater shrinkage of tumor spheroids.

    Science.gov (United States)

    Baek, Jong-Suep; Choo, Chee Chong; Tan, Nguan Soon; Loo, Say Chye Joachim

    2017-10-06

    Polymeric particulate delivery systems are vastly explored for the delivery of chemotherapeutic agents. However, the preparation of polymeric particulate systems with the capability of providing sustained release of two or more drugs is still a challenge. Herein, poly (D, L-lactic-co-glycolic acid, 50:50) hollow microparticles co-loaded with doxorubicin and paclitaxel were developed through double-emulsion solvent evaporation technique. Hollow microparticles were formed through the addition of an osmolyte into the fabrication process. The benefits of hollow over solid microparticles were found to be higher encapsulation efficiency and a more rapid drug release rate. Further modification of the hollow microparticles was accomplished through the introduction of methyl-β-cyclodextrin. With this, a higher encapsulation efficiency of both drugs and an enhanced cumulative release were achieved. Spheroid study further demonstrated that the controlled release of the drugs from the methyl-β-cyclodextrin -loaded hollow microparticles exhibited enhanced tumor regressions of MCF-7 tumor spheroids. Such hollow dual-drug-loaded hollow microparticles with sustained releasing capabilities may have a potential for future applications in cancer therapy.

  17. Evaluation of rate of swelling and erosion of verapamil (VRP) sustained-release matrix tablets.

    Science.gov (United States)

    Khamanga, Sandile M; Walker, Roderick B

    2006-01-01

    Tablets manufactured in-house were compared to a marketed sustained-release product of verapamil to investigate the rate of hydration, erosion, and drug-release mechanism by measuring the wet and subsequent dry weights of the products. Swelling and erosion rates depended on the polymer and granulating fluid used, which ultimately pointed to their permeability characteristics. Erosion rate of the marketed product was highest, which suggests that the gel layer that formed around these tablets was weak as opposed to the robust and resistant layers of test products. Anomalous and near zero-order transport mechanisms were dominant in tests and commercial product, respectively.

  18. Once-Daily, Controlled-Release Tramadol and Sustained-Release Diclofenac Relieve Chronic Pain due to Osteoarthritis: A Randomized Controlled Trial

    Directory of Open Access Journals (Sweden)

    André D Beaulieu

    2008-01-01

    Full Text Available OBJECTIVE: The present study was a randomized, parallel, double-blind comparison between controlled-release (CR tramadol and sustained-release (SR diclofenac in patients with chronic pain due to osteoarthritis of the hips and/or knees.

  19. Experience with sustained-release melatonin for the treatment of sleep disorders in depression

    Directory of Open Access Journals (Sweden)

    Svetlana Vladimirovna Prokhorova

    2015-01-01

    Full Text Available The data available in the literature on the role of melatonin in the regulation of circadian rhythms and sleep disorders in the population and in patients with mental diseases are analyzed. The cause of insomnia may be circadian rhythm disorders due to the age-related decline in the elaboration of the endogenous hormones that are responsible for the quality and duration of sleep, one of which is melatonin.Sustained-release melatonin is a synthetic analogue of the endogenous human pineal hormone melatonin. According to clinical findings, the main proven clinical effects of sustained-release melatonin 2 mg are a reduction in the latency of sleep, improvement of its quality, and lack of daytime sleepiness. The drug causes no dependence on its long use and rebound symptoms (increased insomnia symptoms, positively affects cognitive functions, and lowers nocturnal blood pressure in hypertensive patients.The paper describes a clinical case of a female patient with recurrent depressive disorder, in whom sustained-release melatonin 2 mg has demonstrated high efficacy and good tolerability in the combination therapy of sleep disorders in the pattern of depression.

  20. Development of subcutaneous sustained release nanoparticles encapsulating low molecular weight heparin

    Directory of Open Access Journals (Sweden)

    Satheesh Jogala

    2015-01-01

    Full Text Available The objective of the present research work was to prepare and evaluate sustained release subcutaneous (s.c. nanoparticles of low molecular weight heparin (LMWH. The nanoparticles were prepared by water-in-oil in-water (w/o/w emulsion and evaporation method using different grades of polylactide co-glycolide (50:50, 85:15, and different concentrations of polyvinyl alcohol (0.1%, 0.5%, 1% aqueous solution as surfactant. The fabricated nanoparticles were evaluated for size, shape, zeta potential, encapsulation efficiency, in vitro drug release, and in vivo biological activity (anti-factor Xa activity using the standard kit. The drug and excipient compatibility was analyzed by Fourier transform infrared spectroscopy (FTIR, differential scanning calorimetry (DSC and X-ray diffraction (XRD studies. The formation of nanoparticles was confirmed by scanning electron microscopy; nanoparticles were spherical in shape. The size of prepared nanoparticles was found between 195 nm and 251 nm. The encapsulation efficiency of the nanoparticles was found between 46% and 70%. In vitro drug, release was about 16-38% for 10 days. In vivo drug, release shows the sustained release of drug for 10 days in rats. FTIR studies indicated that there was no loss in chemical integrity of the drug upon fabrication into nanoparticles. DSC and XRD results demonstrated that the drug was changed from the crystalline form to the amorphous form in the formulation during the fabrication process. The results of this study revealed that the s.c. nanoparticles were suitable candidates for sustained delivery of LMWH.

  1. Physical crosslinking modulates sustained drug release from recombinant silk-elastinlike protein polymer for ophthalmic applications.

    Science.gov (United States)

    Teng, Weibing; Cappello, Joseph; Wu, Xiaoyi

    2011-12-10

    We evaluated the drug release capability of optically transparent recombinant silk-elastinlike protein polymer, SELP-47K, films to sustainably deliver the common ocular antibiotic, ciprofloxacin. The ciprofloxacin release kinetics from drug-loaded SELP-47K films treated with ethanol or methanol vapor to induce different densities of physical crosslinking was investigated. Additionally, the drug-loaded protein films were embedded in a protein polymer coating to further prolong the release of the drug. Drug-loaded SELP-47K films released ciprofloxacin for up to 132 h with near first-order release kinetics. Polymer coating of drug-loaded films prolonged drug release for up to 220 h. The antimicrobial activity of ciprofloxacin released from the drug delivery matrices was not impaired by the film casting process or the ethanol or methanol treatments. The mechanism of drug release was elucidated by analyzing the physical properties of the film specimens, including equilibrium swelling, soluble fraction, surface roughness and hydrophobicity. Additionally, the conformation of the SELP-47K and its physical crosslinks in the films was analyzed by FTIR and Raman spectroscopy. A three-parameter physics based model accurately described the release rates observed for the various film and coating treatments and attributed the effects to the degree of physical crosslinking of the films and to an increasing affinity of the drug with the polymer network. Together, these results indicate that optically transparent silk-elastinlike protein films may be attractive material candidates for novel ophthalmic drug delivery devices. Copyright © 2011 Elsevier B.V. All rights reserved.

  2. Design and in vitro/in vivo evaluation of sustained-release floating tablets of itopride hydrochloride.

    Science.gov (United States)

    Ahmed, Sayed M; Ahmed Ali, Adel; Ali, Ahmed Ma; Hassan, Omiya A

    2016-01-01

    The aim of the present study was to improve the bioavailability of itopride (ITO) and sustain its action by formulating as a floating dosage form. Sustained-release floating tablets of ITO hydrochloride (HCl) were prepared by direct compression using different hydrocolloid polymers such as hydroxypropyl methylcellulose and ethylcellulose and/or methacrylic acid polymers Eudragit RSPM and Carbopol 934P. The floating property was achieved using an effervescent mixture of sodium bicarbonate and anhydrous citric acid (1:1 mol/mol). Hardness, friability, content uniformity, and dissolution rate of the prepared floating tablets were evaluated. The formulation F10 composed of 28.5% Eudragit RSPM, 3% NaHCO3, and 7% citric acid provided sustained drug release. In vitro results showed sustained release of F10 where the drug release percentage was 96.51%±1.75% after 24 hours (P=0.031). The pharmacokinetic results indicated that the area under the curve (AUC0-∞) of the prepared sustained-release floating tablets at infinity achieved 93.69 µg·h/mL compared to 49.89 µg·h/mL for the reference formulation (Ganaton(®)) and the relative bioavailability of the sustained-release formulation F10 increased to 187.80% (P=0.022). The prepared floating tablets of ITO HCl (F10) could be a promising drug delivery system with sustained-release action and enhanced drug bioavailability.

  3. Chitosan based nanoparticles as a sustained protein release carrier for tissue engineering applications

    Science.gov (United States)

    Hou, Yaping; Hu, Junli; Park, Hyejin; Lee, Min

    2012-01-01

    Chitosan/tripolyphosphate/chondroitin sulfate (Chi/TPP/CS) nanoparticles were prepared by an ionic gelation method to obtain a controlled release of proteins. Using Nel-like molecule-1 (Nell-1), a novel osteogenic protein, as a model protein, it was demonstrated that adjusting the composition of the particles modulated the protein association and release kinetics of incorporated proteins. Increasing the amounts of chitosan crosslinking agents, TPP and CS, in the particles achieved sustained protein release. An increase in crosslinking density decreased degradation rates of the particles. Furthermore, the bioactivity of the protein was preserved during the encapsulating procedure into the particles. To demonstrate the feasibility of Chi/TPP/CS nanoparticles as sustained release carriers for tissue engineering scaffold applications, protein-loaded nanoparticles were successfully incorporated into collagen hydrogels or prefabricated porous poly (lactide-co-glycolide) (PLGA) scaffolds without obstructing the integrity of the hydrogels or porous structure of the scaffolds. Thus, we expect that these particles have a potential for efficient protein carriers in tissue engineering applications, and will be further evaluated in vivo. PMID:22275184

  4. Synthesis of multilayered alginate microcapsules for the sustained release of fibroblast growth factor-1

    Science.gov (United States)

    Khanna, Omaditya; Moya, Monica L; Opara, Emmanuel C; Brey, Eric M

    2010-01-01

    Alginate microcapsules coated with a permselective poly-L-ornithine (PLO) membrane have been investigated for the encapsulation and transplantation of islets as a treatment for type 1 diabetes. The therapeutic potential of this approach could be improved through local stimulation of microvascular networks in order to meet mass transport demands of the encapsulated cells. Fibroblast growth factor-1 (FGF-1) is a potent angiogenic factor with optimal effect occurring when it is delivered in a sustained manner. In this paper, a technique is described for the generation of multilayered alginate microcapsules with an outer alginate layer that can be used for the delivery of FGF-1. The influence of alginate concentration and composition (high mannuronic acid (M) or guluronic acid (G) content) on outer layer size and stability, protein encapsulation efficiency, and release kinetics was investigated. The technique results in a stable outer layer of alginate with a mean thickness between 113–164 µm, increasing with alginate concentration and G-content. The outer layer was able to encapsulate and release FGF-1 for up to thirty days, with 1.25% of high G alginate displaying the most sustained release. The released FGF-1 retained its biologic activity in the presence of heparin, and the addition of the outer layer did not alter the permselectivity of the PLO coat. This technique could be used to generate encapsulation systems that deliver proteins to stimulate local neovascularization around encapsulated islets. PMID:20725969

  5. Polypyrrole nanoparticles for tunable, pH-sensitive and sustained drug release

    Science.gov (United States)

    Samanta, Devleena; Meiser, Jana L.; Zare, Richard N.

    2015-05-01

    We report the development of a generalized pH-sensitive drug delivery system that can release any charged drug preferentially at the pH range of interest. Our system is based on polypyrrole nanoparticles (PPy NPs), synthesized via a simple one-step microemulsion technique. These nanoparticles are highly monodisperse, stable in solution over the period of a month, and have good drug loading capacity (~15 wt%). We show that PPy NPs can be tuned to release drugs at both acidic and basic pH by varying the pH, the charge of the drug, as well as by adding small amounts of charged amphiphiles. Moreover, these NPs may be delivered locally by immobilizing them in a hydrogel. Our studies show encapsulation within a calcium alginate hydrogel results in sustained release of the incorporated drug for more than 21 days. Such a nanoparticle-hydrogel composite drug delivery system is promising for treatment of long-lasting conditions such as cancer and chronic pain which require controlled, localized, and sustained drug release.

  6. Chlorhexidine sustained-release varnishes for catheter coating - Dissolution kinetics and antibiofilm properties.

    Science.gov (United States)

    Gefter Shenderovich, Julia; Zaks, Batya; Kirmayer, David; Lavy, Eran; Steinberg, Doron; Friedman, Michael

    2018-01-15

    Catheter-associated urinary tract infections are difficult to eradicate or prevent, due to their biofilm-related nature. Chlorhexidine, a widely used antiseptic, was previously found to be effective against catheter-related biofilms. For the present study, we developed sustained-release chlorhexidine varnishes for catheter coating and evaluated their antibiofilm properties and chlorhexidine-dissolution kinetics under various conditions. The varnishes were based on ethylcellulose or ammonio methacrylate copolymer type A (Eudragit® RL). Chlorhexidine was released by diffusion from a heterogeneous matrix in the case of the ethylcellulose-based formulation, and from a homogeneous matrix in the case of Eudragit® RL. This dictated the release pattern of chlorhexidine under testing conditions: from film specimens, and from coated catheters in a static or flow-through system. Momentary saturation was observed with the flow-through system in Eudragit® RL-based coatings, an effect that might be present in vivo with other formulations as well. The coatings were retained on the catheters for at least 2weeks, and showed prolonged activity in a biological medium, including an antibiofilm effect against Pseudomonas aeruginosa. The current study demonstrates the potential of catheter coatings with sustained release of chlorhexidine in the prevention of catheter-associated urinary tract infections. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Sustained release gastroretentive tablet of metformin hydrochloride based on poly (acrylic acid)-grafted-gellan.

    Science.gov (United States)

    Sarkar, Debjani; Nandi, Gouranga; Changder, Abhijit; Hudati, Prasenjit; Sarkar, Sayani; Ghosh, Lakshmi Kanta

    2017-03-01

    Development of a gastroretentive sustained release tablet of metformin based on poly (acrylic acid)-grafted-gellan (PAAc-g-GG) is the main purpose of this study. At first, PAAc-g-GG was synthesized by microwave-promoted free radical initiation method using cerric (IV) ammonium nitrate (CAN) as redox initiator and characterized by elemental analysis, FTIR, DSC-TGA, (13)C NMR, biodegradation and viscosity study. The synthetic parameters were optimized by 2(3) full factorial design using Design Expert software. Acute oral toxicity and histological studies were also performed as per OECD guideline. Tablets were then prepared employing wet granulation method using PAAc-g-GG and evaluated for various physical characters, in vitro drug release, ex-vivo mucoadhesion and swelling. Compatibility between drug and excipients was checked by DSC and FTIR analysis. The F3 batch showed excellent mucoadhesion and sustained drug release over a period of 10h with dissolution similarity factor, f2=77.43. Kinetic modeling unveiled Case-1 Fickian diffusion based drug release mechanism. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Chitosan-based nanoparticles as a sustained protein release carrier for tissue engineering applications.

    Science.gov (United States)

    Hou, Yaping; Hu, Junli; Park, Hyejin; Lee, Min

    2012-04-01

    Chitosan/tripolyphosphate/chondroitin sulfate (Chi/TPP/CS) nanoparticles were prepared by an ionic gelation method to obtain a controlled release of proteins. Using Nel-like molecule-1 (Nell-1), a novel osteogenic protein, as a model protein, it was demonstrated that adjusting the composition of the particles modulated the protein association and release kinetics of incorporated proteins. Increasing the amounts of Chi crosslinking agents, TPP and CS, in the particles achieved sustained protein release. An increase in crosslinking density decreased degradation rates of the particles. Furthermore, the bioactivity of the protein was preserved during the encapsulating procedure into the particles. To demonstrate the feasibility of Chi/TPP/CS nanoparticles as sustained release carriers for tissue engineering scaffold applications, protein-loaded nanoparticles were successfully incorporated into collagen hydrogels or prefabricated porous poly(lactide-co-glycolide) (PLGA) scaffolds without obstructing the integrity of the hydrogels or porous structure of the scaffolds. Thus, we expect that these particles have a potential for efficient protein carriers in tissue engineering applications, and will be further evaluated in vivo. Copyright © 2012 Wiley Periodicals, Inc.

  9. Physical solid-state properties and dissolution of sustained-release matrices of polyvinylacetate.

    Science.gov (United States)

    Gonzalez Novoa, Gelsys Ananay; Heinämäki, Jyrki; Mirza, Sabir; Antikainen, Osmo; Colarte, Antonio Iraizoz; Paz, Alberto Suzarte; Yliruusi, Jouko

    2005-02-01

    Solid-state compatibility and in vitro dissolution of direct-compressed sustained-release matrices of polyvinylacetate (PVAc) and polyvinylpyrrolidone (PVP) containing ibuprofen as a model drug were studied. Polyvinylalcohol (PVA) was used as an alternative water-soluble polymer to PVP. Differential scanning calorimetry (DSC) and powder X-ray diffractometry (PXRD) were used for characterizing solid-state polymer-polymer and drug-polymer interactions. The mechanical treatment for preparing physical mixtures of polyvinyl polymers and the drug (i.e. simple blending or stressed cogrinding) was shown not to affect the physical state of the drug and the polymers. With the drug-polymer mixtures the endothermic effect due to drug melting was always evident, but a considerable modification of the melting point of the drug in physical binary mixtures (drug:PVP) was observed, suggesting some interaction between the two. On the other hand, the lack of a significant shift of the melting endothermic peak of the drug in physical tertiary drug-polymer mixtures revealed no evidence of solid-state interaction between the drug and the present polymers. Sustained-release dissolution profiles were achieved from the direct-compressed matrices made from powder mixtures of the drug and PVAc combined with PVP, and the proportion of PVAc in the mixture clearly altered the drug release profiles in vitro. The drug release from the present matrix systems is controlled by both diffusion of the drug through the hydrate matrix and the erosion of the matrix itself.

  10. Sustained and controlled release of lipophilic drugs from a self-assembling amphiphilic peptide hydrogel

    DEFF Research Database (Denmark)

    Briuglia, Maria-Lucia; Urquhart, Andrew; Lamprou, Dimitrios A.

    2014-01-01

    Materials which undergo self-assembly to form supramolecular structures can provide alternative strategies to drug loading problems in controlled release application. RADA 16 is a simple and versatile self-assembling peptide with a designed structure formed of two distinct surfaces, one hydrophilic...... and one hydrophobic that are positioned in such a well-ordered fashion allowing precise assembly into a predetermined organization. A "smart" architecture in nanostructures can represent a good opportunity to use RADA16 as a carrier system for hydrophobic drugs solving problems of drugs delivery....... In this work, we have investigated the diffusion properties of Pindolol, Quinine and Timolol maleate from RADA16 in PBS and in BSS-PLUS at 37°C. A sustained, controlled, reproducible and efficient drug release has been detected for all the systems, which allows to understand the dependence of release kinetics...

  11. Adolescent Female Cannabinoid Exposure Diminishes the Reward-Facilitating Effects of Δ9-Tetrahydrocannabinol and d-Amphetamine in the Adult Male Offspring

    Directory of Open Access Journals (Sweden)

    George Panagis

    2017-04-01

    Full Text Available Marijuana is currently the most commonly abused illicit drug. According to recent studies, cannabinoid use occurring prior to pregnancy can impact brain plasticity and behavior in future generations. The purpose of the present study was to determine whether adolescent exposure of female rats to Δ9-tetrahydrocannabinol (Δ9-THC induces transgenerational effects on the reward-facilitating effects of Δ9-THC and d-amphetamine in their adult male offspring. Female Sprague-Dawley rats received Δ9-THC (0.1 or 1 mg/kg, i.p. or vehicle during postnatal days 28–50. As adults, females were mated with drug-naïve males. We then assessed potential alterations of the Δ9-THC’s (0, 0.1, 0.5, and 1 mg/kg, i.p. and d-amphetamine’s (0, 0.1, 0.5, and 1 mg/kg, i.p. reward-modifying effects using the curve-shift variant of the intracranial self-stimulation (ICSS procedure in their adult male F1 offspring. The reward-facilitating effect of the 0.1 mg dose of Δ9-THC was abolished in the F1 offspring of females that were exposed to Δ9-THC (0.1 or 1 mg/kg, whereas the reward-attenuating effect of the 1 mg dose of Δ9-THC remained unaltered. The reward-facilitating effects of 0.5 and 1 mg of d-amphetamine were significantly decreased in the F1 offspring of females that were exposed to Δ9-THC (1 mg/kg and 0.1 or 1 mg, respectively. The present results reveal that female Δ9-THC exposure during adolescence can diminish the reward-facilitating effects of Δ9-THC and d-amphetamine in the adult male offspring. These transgenerational effects occur in the absence of in utero exposure. It is speculated that Δ9-THC exposure during female adolescence may affect neural mechanisms that are shaping reward-related behavioral responses in a subsequent generation, as indicated by the shifts in the reward-facilitating effects of commonly used and abused drugs.

  12. Bupropion sustained release for pregnant smokers: a randomized, placebo-controlled trial.

    Science.gov (United States)

    Nanovskaya, Tatiana N; Oncken, Cheryl; Fokina, Valentina M; Feinn, Richard S; Clark, Shannon M; West, Holly; Jain, Sunil K; Ahmed, Mahmoud S; Hankins, Gary D V

    2017-04-01

    Bupropion is used to treat depression during pregnancy. However, its usefulness as a smoking cessation aid for pregnant women is not fully known. The objective of the study was to evaluate the preliminary efficacy of bupropion sustained release for smoking cessation during pregnancy. We conducted a randomized, prospective, double-blind, placebo-controlled, pilot trial. Pregnant women who smoked daily received individualized behavior counseling and were randomly assigned to a 12 week, twice-a-day treatment with 150 mg bupropion sustained release or placebo. The primary study objectives were to determine whether bupropion sustained release reduces nicotine withdrawal symptoms on the quit date and during the treatment period compared with placebo and whether it increases 7 day point prevalence abstinence at the end of the treatment period and at the end of pregnancy. Subjects in the bupropion (n = 30) and placebo (n = 35) groups were comparable in age, smoking history, number of daily smoked cigarettes, and nicotine dependence. After controlling for maternal age and race, bupropion sustained release reduced cigarette cravings (1.5 ± 1.1 vs 2.1 ± 1.2, P = .02) and total nicotine withdrawal symptoms (3.8 ± 4.3 vs 5.4 ± 5.1, P = .028) during the treatment period. Administration of bupropion sustained release reduced tobacco exposure, as determined by levels of carbon monoxide in exhaled air (7.4 ± 6.4 vs 9.1 ± 5.8, P = .053) and concentrations of cotinine in urine (348 ± 384 ng/mL vs 831 ± 727 ng/mL, P = .007) and increased overall abstinence rates during treatment (19% vs 2%, P = .003). However, there was no significant difference in 7 day point prevalence abstinence rates between the 2 groups at the end of medication treatment (17% vs 3%, P = .087) and at the end of pregnancy (10% vs 3%, P = .328). Individual smoking cessation counseling along with the twice-daily use of 150 mg bupropion

  13. Development of indomethacin sustained release microcapsules using chitosan-carboxymethylcellulose complex coacervation

    Directory of Open Access Journals (Sweden)

    Garnpimol C. Ritthidej

    2003-05-01

    Full Text Available Indomethacin sustained release microcapsules were prepared by complex coacervation of chitosan (CS and carboxymethylcellulose (CMC and then were hardened with glutaraldehyde (GA. The effects of concentration and pH of CS solution, amount of GA and hardening time on the physicochemical properties and drug release of these microcapsules were investigated. The SEM photomicrographs revealed that surface morphology of microcapsules depended on the pH of CS solution. Decreasing the pH increased the smoothness of the surface due to the relaxation of CS chain in acidic medium. The geometric mean diameters of the microcapsules were between 126-212 microns. Those prepared from CS solution of pH 4 and hardening time of 3 hours seemed to have the narrowest size distribution. The percent drug entrapment was comparable in the range of 40%-50% while the percent drug recovery varied between 60%-87%. The latter increased when decreasing the pH and increasing the concentration of CS solution but decreased when increasing the hardening time. Dissolution study showed that microcapsules prepared from CS solution of high pH initially released the drug faster than those from CS solution of lower pH. After 3 hours their release rate was similar.Increasing the amount of GA and hardening time decreased the drug release due to denser membrane. In contrast, the concentration of CS solution had no effect on drug release. The mechanism of drug release was prominently diffusion controlled through wall membrane and pore. The kinetics of drug release followed Higuchi’s model.

  14. Generic sustained release tablets of trimetazidine hydrochloride: Preparation and in vitro–in vivo correlation studies

    Directory of Open Access Journals (Sweden)

    Longmei Wang

    2016-06-01

    Full Text Available The aim of the current work was to develop generic sustained-release tablets containing 35 mg trimetazidine dihydrochloride and to establish an in vitro–in vivo correlation that could predict the bioavailability. The marketed sustained release tablet (Vastarel MR used as reference, a sustained-release matrix tablet was prepared using hydroxypropyl methylcellulose (HPMC as matrix by wet granulation and the in vitro dissolution profiles of the self-made tablets were determined in four different dissolution media (0.1 M HCl, pH 4.5 PBS, pH 6.8 PBS and water. A higher similarity between prepared tablets and Vastarel MR was established, with similarity factor (f2 ranging from 60 to 75 in the four media. The in vivo pharmacokinetics was studied in six healthy beagles. Compared with Vastarel MR, the Cmax of self-made tablets was slightly decreased, while the Tmax and MRT0–t were slightly prolonged, but with no significant difference (P > 0.05. The average of relative bioavailability (F was 102.52% based on AUC0–t. For log-transformed AUC0–t and Cmax, the upper confidence limit on the appropriate criterion is <0, indicating these two formulations were population bioequivalent. The in vivo–in vitro correlation coefficient obtained from point-to-point analysis of self-made tablets was 0.9720. In conclusion, the prepared tablets were bioequivalent to the marketed tablets, according to both the in vitro release rate and extent of absorption, and a good in vivo–in vitro correlation was established for the self-made tablets that indicated in vitro dissolution tests could be used as a surrogate for bioavailability studies.

  15. Sustained nitric oxide (NO)-releasing compound reverses dysregulated NO signal transduction in priapism

    Science.gov (United States)

    Lagoda, Gwen; Sezen, Sena F.; Hurt, K. Joseph; Cabrini, Marcelo R.; Mohanty, Dillip K.; Burnett, Arthur L.

    2014-01-01

    We evaluated the therapeutic potential of a sustained nitric oxide (NO)-releasing compound to correct the molecular hallmarks and pathophysiology of priapism, an important but poorly characterized erectile disorder. 1,5-Bis-(dihexyl-N-nitrosoamino)-2,4-dinitrobenzene (C6′) and an inactive form of the compound [1,5-bis-(dihexylamino)-2,4-dinitrobenzene (C6)] were tested in neuronal cell cultures and penile lysates for NO release (Griess assay) and biological activity (cGMP production). The effect of local depot C6′ or C6 was evaluated in mice with a priapic phenotype due to double neuronal and endothelial NO synthase deletion (dNOS−/−) or human sickle hemoglobin transgenic expression (Sickle). Changes in NO signaling molecules and reactive oxygen species (ROS) surrogates were assessed by Western blot. The physiological response after C6′ treatment was assessed using an established model of electrically stimulated penile erection. C6′ generated NO, increased cGMP, and dose dependently increased NO metabolites. C6′ treatment reversed abnormalities in key penile erection signaling molecules, including phosphodiesterase type 5, phosphorylated endothelial nitric oxide synthase, and phosphorylated vasodilator-stimulated phosphoprotein. In Sickle mice, C6′ also attenuated the increased ROS markers gp91phox, 4-hydroxynonenal, and 3-nitrotyrosine. Finally, C6′ corrected the excessive priapic erection response of dNOS−/− mice. Exogenous sustained NO release from C6′ corrects pathological erectile signaling in mouse models of priapism and suggests novel approaches to human therapy.—Lagoda, G., Sezen, S. F., Hurt, K. J., Cabrini, M. R., Mohanty, D. K., Burnett, A. L. Sustained nitric oxide (NO)-releasing compound reverses dysregulated NO signal transduction in priapism. PMID:24076963

  16. PLGA-Based Microparticles for the Sustained Release of BMP-2

    Directory of Open Access Journals (Sweden)

    Maria A. Woodruff

    2011-03-01

    Full Text Available The development of growth factor delivery strategies to circumvent the burst release phenomenon prevalent in most current systems has driven research towards encapsulating molecules in resorbable polymer matrices. For these polymer release techniques to be efficacious in a clinical setting, several key points need to be addressed. This present study has investigated the encapsulation of the growth factor, BMP-2 within PLGA/PLGA-PEG-PLGA microparticles. Morphology, size distribution, encapsulation efficiency and release kinetics were investigated and we have demonstrated a sustained release of bioactive BMP-2. Furthermore, biocompatibility of the PLGA microparticles was established and released BMP-2 was shown to promote the differentiation of MC3T3-E1 cells towards the osteogenic lineage to a greater extent than osteogenic supplements (as early as day 10 in culture, as determined using alkaline phosphatase and alizarin red assays. This study showcases a potential BMP-2 delivery system which may now be translated into more complex delivery systems, such as 3D, mechanically robust scaffolds for bone tissue regeneration applications.

  17. Development of transdermal system containing nicotine by using sustained release dosage design.

    Science.gov (United States)

    Tirnaksiz, Figen; Yuce, Zeynep

    2005-09-01

    This study was carried out to develop a membrane-controlled transdermal formulation (TF) of nicotine by using sustained release dosage design (SRDD). TFs were prepared with polyethylene membrane as a rate-controlling barrier; a carbomer was used as the gel reservoir with or without propylene glycol (PG). The in vitro target flux (0.0535 mg cm(-2) h(-1)) was calculated according to SRDD calculations. Nicotine permeation through the membrane with or without transfer adhesive was also studied using diffusion cells. Nicotine permeated through membrane (without adhesive) with a flux of 0.0555 mg cm(-2) h(-1) and this value was similar to that of the in vitro target flux. The release from the TFs and from a commercial product (Nicotinell, 52.5 mg 30 cm(-2)) was studied using the FDA paddle method. The nicotine amount was increased from 22.7 to 56.5 mg in gel reservoir, and a plateau was reached beyond 45.4 mg of drug; the system attained the maximum thermodynamic activity with 56.5 mg of nicotine. The release rate from TFs (without adhesive layer) containing PG in the reservoir was very similar to the target release rate (1.07 mg h(-1)). The fluxes of nicotine from Nicotinell and TF containing 45.4 mg of nicotine were close to the in vitro target release rate.

  18. Transformations of Nanoenabled Copper Formulations Govern Release, Antifungal Effectiveness, and Sustainability throughout the Wood Protection Lifecycle.

    Science.gov (United States)

    Pantano, Daniele; Neubauer, Nicole; Navratilova, Jana; Scifo, Lorette; Civardi, Chiara; Stone, Vicki; von der Kammer, Frank; Müller, Philipp; Sobrido, Marcos Sanles; Angeletti, Bernard; Rose, Jerome; Wohlleben, Wendel

    2018-02-06

    Here we compare the standard European benchmark of wood treatment by molecularly dissolved copper amine (Cu-amine), also referred to as aqueous copper amine (ACA), against two nanoenabled formulations: copper(II)oxide nanoparticles (CuO NPs) in an acrylic paint to concentrate Cu as a barrier on the wood surface, and a suspension of micronized basic copper carbonate (CuCO 3 ·Cu(OH) 2 ) for wood pressure treatment. After characterizing the properties of the (nano)materials and their formulations, we assessed their effects in vitro against three fungal species: Coniophora puteana, Gloeophyllum trabeum, and Trametes versicolor, finding them to be mediated only partially by ionic transformation. To assess the use phase, we quantify both release rate and form. Cu leaching rates for the two types of impregnated wood (conventional and nanoenabled) are not significantly different at 172 ± 6 mg/m 2 , with Cu being released predominantly in ionic form. Various simulations of outdoor aging with release sampling by runoff, during condensation, by different levels of mechanical shear, all resulted in comparable form and rate of release from the nanoenabled or the molecular impregnated woods. Because of dissolving transformations, the nanoenabled impregnation does not introduce additional concern over and above that associated with the traditional impregnation. In contrast, Cu released from wood coated with the CuO acrylate contained particles, but the rate was at least 100-fold lower. In the same ranking, the effectiveness to protect against the wood-decaying basidiomycete Coniophora puteana was significant with both impregnation technologies but remained insignificant for untreated wood and wood coated by the acrylic CuO. Accordingly, a lifecycle-based sustainability analysis indicates that the CuO acrylic coating is less sustainable than the technological alternatives, and should not be developed into a commercial product.

  19. Polyacrylamide-chitosan hydrogels: in vitro biocompatibility and sustained antibiotic release studies.

    Science.gov (United States)

    Risbud, M V; Bhonde, R R

    2000-01-01

    Controlled drug delivery is gaining importance over the conventional methods of drug administration because of its inherent benefits. Self-regulated release from the delivery vehicle may enhance drug potency with a sustained action. The present study describes a novel hydrogel blend of polyacrylamide with chitosan for controlled delivery of antibiotics. Hydrogel was synthesized by cross-linking acrylamide-chitosan mixture (8:2 v/v) with N,N' methylene bisacrylamide. Hydrogel was characterized for surface morphology, hydrophilicity, pH-dependent swelling properties, cytotoxicity, and control release properties. Scanning electron microscopy (SEM) revealed the macroporous surface morphology of the matrix with average pore size at 104 +/- 7.61 mu. Hydrogel was found to be highly hydrophilic as assessed by octane contact angle (154.5 + 0.572) measurement. Hydrogel showed no cytotoxic effects on NIH3T3 and HeLa cells up to 40% of extract concentrations as determined by MTT and neutral red assay. This showed hydrogel biocompatibility and thus absence of deleterious effects of the hydrogel on cell viability and functionality. Hydrogels did not show any pH-dependent swelling profile, and they swelled considerably to achieve a swelling ratio of approximately 16.0 at the end of 24 hr. Amoxicillin was incorporated in the hydrogel matrix as a candidate antibiotic for release studies. In vitro release studies of amoxicillin revealed the sustained nature of delivery and matrix released 56.47 + 1.12% and 77.096 + 1.72% of amoxicillin at the end of 24 and 75 hr, respectively. Although in vivo studies are awaited, the present study provides enough documentation to consider polyacrylamide-chiotsan hydrogel as a possible candidate for controlled delivery of antibiotics.

  20. High-throughput NIR-chemometric methods for chemical and pharmaceutical characterization of sustained release tablets.

    Science.gov (United States)

    Porfire, Alina; Filip, Cristina; Tomuta, Ioan

    2017-05-10

    The aim of this study was the development and validation of methods based on near-infrared spectroscopy (NIRS) and chemometry, useful for characterization of sustained release (SR) tablets with indapamide, in terms of tablet composition (API and two excipients), in vitro drug release mechanism (k and n Peppas) and crushing strength. A calibration set consisting of 25 different tablets formulations containing API, HPMC and lactose at five different content levels in the range 100±20% relative to a targeted tablet composition, were manufactured by direct compression in order to develop the methods for prediction of tablet composition, and in vitro drug release mechanism. On the other hand, a 15 batches calibration set prepared at five different compression forces was used for development of methods for prediction of crushing strength. Moreover, independent batches were manufactured for validation of all methods Intact tablets were analyzed by transmission mode with NIRS, the spectra were pre-processed, and partial least square (PLS) regression was used to build prediction models. Cross-validation was carried out in order to select the optimal number of PLS factors for all models, and the best model was chosen based on their RMSECV and bias. All developed methods were validated in terms of trueness, precision and accuracy. Based on the validation results, the methods proposed in this work can successfully be applied for routine determination of indapamide, HPMC and lactose content of sustained release tablets, as well as for prediction of their in vitro drug release mechanism (k and n Peppas) and crushing strength. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. A Preliminary Investigation of Individual Differences in Subjective Responses to D-Amphetamine, Alcohol, and Delta-9-Tetrahydrocannabinol Using a Within-Subjects Randomized Trial.

    Directory of Open Access Journals (Sweden)

    Margaret C Wardle

    Full Text Available Polydrug use is common, and might occur because certain individuals experience positive effects from several different drugs during early stages of use. This study examined individual differences in subjective responses to single oral doses of d-amphetamine, alcohol, and delta-9-tetrahydrocannabinol (THC in healthy social drinkers. Each of these drugs produces feelings of well-being in at least some individuals, and we hypothesized that subjective responses to these drugs would be positively correlated. We also examined participants' drug responses in relation to personality traits associated with drug use. In this initial, exploratory study, 24 healthy, light drug users (12 male, 12 female, aged 21-31 years, participated in a fully within-subject, randomized, counterbalanced design with six 5.5-hour sessions in which they received d-amphetamine (20mg, alcohol (0.8 g/kg, or THC (7.5 mg, each paired with a placebo session. Participants rated the drugs' effects on both global measures (e.g. feeling a drug effect at all and drug-specific measures. In general, participants' responses to the three drugs were unrelated. Unexpectedly, "wanting more" alcohol was inversely correlated with "wanting more" THC. Additionally, in women, but not in men, "disliking" alcohol was negatively correlated with "disliking" THC. Positive alcohol and amphetamine responses were related, but only in individuals who experienced a stimulant effect of alcohol. Finally, high trait constraint (or lack of impulsivity was associated with lower reports of liking alcohol. No personality traits predicted responses across multiple drug types. Generally, these findings do not support the idea that certain individuals experience greater positive effects across multiple drug classes, but instead provide some evidence for a "drug of choice" model, in which individuals respond positively to certain classes of drugs that share similar subjective effects, and dislike other types

  2. Calcium-Alginate Hydrogel-Encapsulated Fibroblasts Provide Sustained Release of Vascular Endothelial Growth Factor

    Science.gov (United States)

    Hunt, Nicola C.; Shelton, Richard M.; Henderson, Deborah J.

    2013-01-01

    Vascularization of engineered or damaged tissues is essential to maintain cell viability and proper tissue function. Revascularization of the left ventricle (LV) of the heart after myocardial infarction is particularly important, since hypoxia can give rise to chronic heart failure due to inappropriate remodeling of the LV after death of cardiomyocytes (CMs). Fibroblasts can express vascular endothelial growth factor (VEGF), which plays a major role in angiogenesis and also acts as a chemoattractant and survival factor for CMs and cardiac progenitors. In this in vitro model study, mouse NIH 3T3 fibroblasts encapsulated in 2% w/v Ca-alginate were shown to remain viable for 150 days. Semiquantitative reverse transcription–polymerase chain reaction and immunohistochemistry demonstrated that over 21 days of encapsulation, fibroblasts continued to express VEGF, while enzyme-linked immunosorbent assay showed that there was sustained release of VEGF from the Ca-alginate during this period. The scaffold degraded gradually over the 21 days, without reduction in volume. Cells released from the Ca-alginate at 7 and 21 days as a result of scaffold degradation were shown to retain viability, to adhere to fibronectin in a normal manner, and continue to express VEGF, demonstrating their potential to further contribute to maintenance of cardiac function after scaffold degradation. This model in vitro study therefore demonstrates that fibroblasts encapsulated in Ca-alginate provide sustained release of VEGF. PMID:23082964

  3. Double-layer weekly sustained release transdermal patch containing gestodene and ethinylestradiol.

    Science.gov (United States)

    Gao, Yanli; Liang, Jinying; Liu, Jianping; Xiao, Yan

    2009-07-30

    The combination therapy of gestodene (GEST) and ethinylestradiol (EE) has shown advanced contraception effect and lower side effect. The present study was designed to develop a weekly sustained release matrix type transdermal patch containing GEST and EE using blends of different polymeric combinations. The multiple-layer technique was adopted in order to maintain a steady permeation flux for 7 days. The effects of polymer types, polymer ratios, permeation enhancers, drug loadings and drug ratios in different layers on the skin permeations of the drugs were evaluated using excised mice skin. Polariscope examination was carried out to observe the drug distribution behavior. The formulation with the mixture of polyvinyl alcohol (PVA) and polyvinyl pyrrolidone (PVP) (7:1) was found to provide the regular release and propylene glycol (PG) could enhance the permeation fluxes of drugs. Double-layer transdermal drug delivery system (TDDS) could sustain the steady permeation flux of drugs for 7 days when the ratio of drug in drug release layer and drug reservoir layer was 1:4 with the identical total drug amount. The in vitro transdermal permeation fluxes were 0.377 microg/cm(2)/h and 0.092 microg/cm(2)/h, for GEST and EE respectively. The uniformity of dosage units test showed that the distribution of drugs in the matrix was homogeneous, which was further demonstrated by the polariscope result. The developed transdermal delivery system containing GEST and EE could be a promising non-oral contraceptive method.

  4. Surface modified zeolite-based granulates for the sustained release of diclofenac sodium.

    Science.gov (United States)

    Serri, Carla; de Gennaro, Bruno; Quagliariello, Vincenzo; Iaffaioli, Rosario Vincenzo; De Rosa, Giuseppe; Catalanotti, Lilia; Biondi, Marco; Mayol, Laura

    2017-03-01

    In this study, a granulate for the oral controlled delivery of diclofenac sodium (DS), an anionic sparingly soluble nonsteroidal anti-inflammatory drug, has been realized by wet granulation, using a surface modified natural zeolite (SMNZ) as an excipient. The surface modification of the zeolite has been achieved by means of a cationic surfactant, so as to allow the loading of DS through ionic interaction and bestow a control over the drug release mechanism. The granules possessed a satisfactory dosage uniformity, a flowability suitable for an oral dosage form manufacturing, along with a sustained drug release up to 9h, driven by both ion exchange and transport kinetics. Furthermore, the obtained granulate did not elicit a significant cytotoxicity and could also induce a prolonged anti-inflammatory effect on RAW264.7 cells. Taking also into account that natural zeolites are generally abundant and economic, SMNZ can be considered as an attracting alternative excipient for the production of granules with sustained release features. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Formulation development and optimization of sustained release matrix tablet of Itopride HCl by response surface methodology and its evaluation of release kinetics.

    Science.gov (United States)

    Bose, Anirbandeep; Wong, Tin Wui; Singh, Navjot

    2013-04-01

    The objective of this present investigation was to develop and formulate sustained release (SR) matrix tablets of Itopride HCl, by using different polymer combinations and fillers, to optimize by Central Composite Design response surface methodology for different drug release variables and to evaluate drug release pattern of the optimized product. Sustained release matrix tablets of various combinations were prepared with cellulose-based polymers: hydroxy propyl methyl cellulose (HPMC) and polyvinyl pyrolidine (pvp) and lactose as fillers. Study of pre-compression and post-compression parameters facilitated the screening of a formulation with best characteristics that underwent here optimization study by response surface methodology (Central Composite Design). The optimized tablet was further subjected to scanning electron microscopy to reveal its release pattern. The in vitro study revealed that combining of HPMC K100M (24.65 MG) with pvp(20 mg)and use of LACTOSE as filler sustained the action more than 12 h. The developed sustained release matrix tablet of improved efficacy can perform therapeutically better than a conventional tablet.

  6. Formulation and in vivo evaluation of diclofenac sodium sustained release matrix tablet: effect of compression force.

    Science.gov (United States)

    Taha, Ehab Ibrahim; Shazly, Gamal Abdel-Ghany; Harisa, Gamaleldin Ibrahim; Barakat, Nahla Sedik; Al-Enazi, Fouza Kayem; Elbagory, Ibrahim Mostafa

    2015-03-01

    In the present study, Diclofenac Sodium (DS) matrix tablets were prepared by direct compression method under different compression forces (5, 10, 15 and 20 KN), using ethylcellulose as matrix forming material. The produced tablets were characterized on the foundation of satisfactory tablet properties such as hardness, friability, drug content, weight variations and in vitro drug release rate. Differential scanning calorimetry (DSC), Fourier Transform Infrared (FT-IR) spectroscopy and X-ray diffraction have been used to investigate any incompatibilities of the tablet's ingredients. Additionally, in vivo bioavailability has been investigated on beagle dogs. Data obtained revealed that, upon increasing compression force the in vitro drug release was sustained and the T(max) value was four hours (for formulations compressed at 15 and 20 kN) compared to the conventional voltarine(®) 50 tablets (T(max) value of 2 hours).

  7. Assembly of a Tripeptide and Anti-Inflammatory Drugs into Supramolecular Hydrogels for Sustained Release

    Directory of Open Access Journals (Sweden)

    Marina Kurbasic

    2017-08-01

    Full Text Available Supramolecular hydrogels offer interesting opportunities for co-assembly with drugs towards sustained release over time, which could be achieved given that the drug participates in the hydrogel nanostructure, and it is not simply physically entrapped within the gel matrix. dLeu-Phe-Phe is an attractive building block of biomaterials in light of the peptide’s inherent biocompatibility and biodegradability. This study evaluates the assembly of the tripeptide in the presence of either of the anti-inflammatory drugs ketoprofen or naproxen at levels analogous to commercial gel formulations. Fourier-transformed infrared (FT-IR, circular dichroism, Thioflavin T fluorescence, transmission electron microscopy (TEM, and oscillatory rheometry are used. Drug release over time is monitored by means of reverse-phase high performance liquid chromatography, and shows different kinetics for the two drugs.

  8. Modular approach for bimodal antibacterial surfaces combining photo-switchable activity and sustained biocidal release.

    Science.gov (United States)

    Pallavicini, Piersandro; Bassi, Barbara; Chirico, Giuseppe; Collini, Maddalena; Dacarro, Giacomo; Fratini, Emiliano; Grisoli, Pietro; Patrini, Maddalena; Sironi, Laura; Taglietti, Angelo; Moritz, Marcel; Sorzabal-Bellido, Ioritz; Susarrey-Arce, Arturo; Latter, Edward; Beckett, Alison J; Prior, Ian A; Raval, Rasmita; Diaz Fernandez, Yuri A

    2017-07-12

    Photo-responsive antibacterial surfaces combining both on-demand photo-switchable activity and sustained biocidal release were prepared using sequential chemical grafting of nano-objects with different geometries and functions. The multi-layered coating developed incorporates a monolayer of near-infrared active silica-coated gold nanostars (GNS) decorated by silver nanoparticles (AgNP). This modular approach also enables us to unravel static and photo-activated contributions to the overall antibacterial performance of the surfaces, demonstrating a remarkable synergy between these two mechanisms. Complementary microbiological and imaging evaluations on both planktonic and surface-attached bacteria provided new insights on these distinct but cooperative effects.

  9. Levels of sirolimus in saliva and blood following oral topical sustained-release varnish delivery system application.

    Science.gov (United States)

    Nudelman, Zakhar; Findler, Mordechai; Barasch, Dinorah; Nemirovski, Alina; Pikovsky, Anna; Kirmayer, David; Basheer, Maamoun; Gutkind, J Silvio; Friedman, Michael; Czerninski, Rakefet

    2015-05-01

    Sirolimus (rapamycin) is a mammalian target of rapamycin pathway blocker. The efficacy of sirolimus is currently studied for its antiproliferative properties in various malignancies and particularly in squamous cell carcinoma and other oral disorders. Topical application at the oral cavity can augment sirolimus availability at the site of action by increasing sirolimus levels in saliva and hence efficacy, along with improved safety (low levels in the blood to avoid side effects) and compliance. Our purpose was to evaluate the release profile and safety of a topical sirolimus sustained-release varnish drug delivery system. Sirolimus sustained-release varnish drug delivery system containing a total of 0.5 mg of the drug was applied to nine healthy male volunteers. Saliva and blood levels were determined utilizing mass spectrometry and chemiluminescent microparticle immunoassay, respectively. The prolonged release profile and safety were evaluated for the oral topical delivery system. After the application of the drug delivery system, a sustained-release profile was observed in the oral cavity. We have measured moderate sirolimus levels for up to 12 h. The safety was confirmed, and systemic sirolimus blood levels were negligible. After an application of sirolimus sustained-release varnish drug delivery system, prolonged drug levels can be achieved in the saliva. The oral topical sirolimus concentrations were potentially therapeutic along with minimal systemic exposure. These results broaden the potential clinical use of sustained-release oral topical rapalogs.

  10. Natural gums as sustained release carriers: development of gastroretentive drug delivery system of ziprasidone HCl

    Directory of Open Access Journals (Sweden)

    AJ Rajamma

    2012-10-01

    Full Text Available Abstract Background Objective of this study is to show the potential use of natural gums in the development of drug delivery systems. Therefore in this work gastro retentive tablet formulations of ziprasidone HCl were developed using simplex lattice design considering concentration of okra gum, locust bean gum and HPMC K4M as independent variables. A response surface plot and multiple regression equations were used to evaluate the effect of independent variables on hardness, flag time, floating time and drug release for 1 h, 2 h, and 8 h and for 24 h. A checkpoint batch was also prepared by considering the constraints and desirability of optimized formulation to improve its in vitro performance. Significance of result was analyzed using ANOVA and p was considered statistically significant. Results Formulation chiefly contains locust bean gum found to be favorable for hardness and floatability but combined effect of three variables was responsible for the sustained release of drug. The in vitro drug release data of check point batch (F8 was found to be sustained well compared to the most satisfactory formulation (F7 of 7 runs. The ‘n’ value was found to be between 0.5 and 1 suggesting that release of drug follows anomalous (non-fickian diffusion mechanism indicating both diffusion and erosion mechanism from these natural gums. Predicted results were almost similar to the observed experimental values indicating the accuracy of the design. In vivo floatability test indicated non adherence to the gastric mucosa and tablets remain buoyant for more than 24 h. Conclusions Study showed these eco-friendly natural gums can be considered as promising SR polymers.

  11. Sustained release of antibiotic from poly(2-hydroxyethyl methacrylate) to prevent blinding infections after cataract surgery.

    Science.gov (United States)

    Anderson, Erin M; Noble, Misty L; Garty, Shai; Ma, Hongyan; Bryers, James D; Shen, Tueng T; Ratner, Buddy D

    2009-10-01

    Intraocular lens implantation after opacified natural lens removal is the primary treatment for cataracts in developed countries. Cataract surgery is generally considered safe, but entails significant risks in countries where sophisticated sterile operating theaters are not widely available. Post-operative infection (endophthalmitis) is a potential blinding complication. Infection often results from bacterial colonization of the new lens implant and subsequent antibiotic-tolerant biofilm formation. To combat this risk, we developed a polymeric hydrogel system that can deliver effective levels of antibiotic over an extended period of time within the globe of the eye. Norfloxacin antibiotic was loaded into cross-linked poly(2-hydroxyethyl methacrylate) (pHEMA) gels, which were subsequently surface-modified with octadecyl isocyanate to produce a hydrophobic rate-limiting barrier controlling norfloxacin release. Octadecyl surface modification was characterized using scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS). A 15-min modification leads to a uniform surface coating and near zero order release of norfloxacin from the matrix. Norfloxacin released from coated pHEMA kills Staphylococcus epidermidis in suspension and on a simulated medical implant surface. With these data, we demonstrate a new and effective system for sustained drug release from a hydrogel matrix with specific application for intraocular lens surgery.

  12. Polycaprolactone scaffold engineered for sustained release of resveratrol: therapeutic enhancement in bone tissue engineering

    Science.gov (United States)

    Kamath, Manjunath Srinivas; Ahmed, Shiek SSJ; Dhanasekaran, M; Santosh, S Winkins

    2014-01-01

    Biomaterials-based three-dimensional scaffolds are being extensively investigated in bone tissue engineering. A potential scaffold should be osteoconductive, osteoinductive, and osteogenic for enhanced bone formation. In this study, a three-dimensional porous polycapro-lactone (PCL) scaffold was engineered for prolonged release of resveratrol. Resveratrol-loaded albumin nanoparticles (RNP) were synthesized and entrapped into a PCL scaffold to form PCL-RNP by a solvent casting and leaching method. An X-ray diffraction study of RNP and PCL-RNP showed that resveratrol underwent amorphization, which is highly desired in drug delivery. Furthermore, Fourier transform infrared spectroscopy indicates that resveratrol was not chemically modified during the entrapment process. Release of resveratrol from PCL-RNP was sustained, with a cumulative release of 64% at the end of day 12. The scaffold was evaluated for its bone-forming potential in vitro using human bone marrow-derived mesenchymal stem cells for 16 days. Alkaline phosphatase activity assayed on days 8 and 12 showed a significant increase in activity (1.6-fold and 1.4-fold, respectively) induced by PCL-RNP compared with the PCL scaffold (the positive control). Moreover, von Kossa staining for calcium deposits on day 16 showed increased mineralization in PCL-RNP. These results suggest PCL-RNP significantly improves mineralization due to its controlled and prolonged release of resveratrol, thereby increasing the therapeutic potential in bone tissue engineering. PMID:24399875

  13. Design and optimization of thermosensitive nanoemulsion hydrogel for sustained-release of praziquantel.

    Science.gov (United States)

    Cong, Zhaotong; Shi, Yanbin; Peng, Xue; Wei, Bei; Wang, Yu; Li, Jincheng; Li, Jianyong; Li, Jiazhong

    2017-04-01

    This work aimed to develop an alternative sustained-release thermosensitive praziquantel-loaded nanoemulsion (PZQ-NE) hydrogel for better schistosomiasis treatment. PZQ-NE-dispersed chitosan/glycerol 2-phosphate disodium/HPMC (NE/CS/β-GP/HMPC) hydrogel was successfully prepared to improve bioavailability of PZQ. Solubility tests and pseudo-ternary phase diagrams were applied to screen optimal oils, surfactants and co-surfactants of NE. The hydrogels were characterized for gelling time, surface exudates, rheological properties and in vitro drug release. Formulation optimization of NE/CS/β-GP/HMPC hydrogel was conducted by Box-Behnken experimental design combined with response surface methodology. In vitro cytotoxicity of hydrogel was studied by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide method. The sustained-release property of PZQ in NE and optimized hydrogel was evaluated by pharmacokinetic study in rabbits. The formulation of PZQ-NE consisted of mass ratio of 12.5% capryol 90 containing PZQ (160 mg/g), 40% cremophor RH 40/tween 20 and transcutol HP (S/CoS = 2:1), 47.5% deionized water. PZQ releasing from NE/CS/β-GP/HMPC hydrogels was best fitted to Higuchi model and governed by diffusion. Rheological investigation evidenced the themosensitive gelation of different hydrogel systems and their gel-like character at 37 °C. The optimized hydrogel formulation consisted of HPMC solution (103.69 mg/g), 3.03% (w/v) chitosan and 14.1% (w/v) β-GP showed no cytotoxicity when the addition of NE was no more than 100 mg/g. Pharmacokinetic parameters indicated that NE/CS/β-GP/HMPC hydrogel can significantly slow down drug elimination, prolong mean residence time and improve bioavailability of PZQ. NE/CS/β-GP/HMPC hydrogel possessed sustained-release property and could be an alternative antischistosomal drug delivery system with improved therapeutic effect.

  14. An investigation of effects of modification processes on physical properties and mechanism of drug release for sustaining drug release from modified rice

    Energy Technology Data Exchange (ETDEWEB)

    Ngo, Vuong Duy; Luu, Thinh Duc; Van Vo, Toi [Pharmaceutical Engineering Laboratory, Biomedical Engineering Department, International University, Vietnam National University, Ho Chi Minh City (Viet Nam); Tran, Van-Thanh [Faculty of Pharmacy, University of Medicine and Pharmacy, Ho Chi Minh City (Viet Nam); Duan, Wei [School of Medicine, Deakin University, Pigdons Road, Waurn Ponds, Victoria (Australia); Tran, Phuong Ha-Lien, E-mail: phuong.tran1@deakin.edu.au [School of Medicine, Deakin University, Pigdons Road, Waurn Ponds, Victoria (Australia); Tran, Thao Truong-Dinh, E-mail: ttdthao@hcmiu.edu.vn [Pharmaceutical Engineering Laboratory, Biomedical Engineering Department, International University, Vietnam National University, Ho Chi Minh City (Viet Nam)

    2016-10-01

    The aim of this study was to investigate the effect of modification processes on physical properties and explain the mechanism of sustained drug release from modified rice (MR). Various types of Vietnamese rice were introduced in the study as the matrices of sustained release dosage form. Rice was thermally modified in water for a determined temperature at different times with a simple process. Then tablets containing MR and isradipine, the model drug, were prepared to investigate the capability of sustained drug release. Scanning electron microscopy (SEM) was used to determine different morphologies between MR formulations. Flow property of MR was analyzed by Hausner ratio and Carr's indices. The dissolution rate and swelling/erosion behaviors of tablets were evaluated at pH 1.2 and pH 6.8 at 37 ± 0.5 °C. The matrix tablet containing MR showed a sustained release as compared to the control. The SEM analyses and swelling/erosion studies indicated that the morphology as well as swelling/erosion rate of MR were modulated by modification time, drying method and incubation. It was found that the modification process was crucial because it could highly affect the granule morphologies and hence, leading to the change of flowability and swelling/erosion capacity for sustained release of drug. - Highlights: • Modification process affected granule morphologies and flowability of modified rice. • Modification process affected swelling/erosion capacity for drug sustained release. • Freeze-drying could decrease the erosion as well as increase the swelling rate.

  15. Effects of naltrexone sustained-release/bupropion sustained-release combination therapy on body weight and glycemic parameters in overweight and obese patients with type 2 diabetes.

    Science.gov (United States)

    Hollander, Priscilla; Gupta, Alok K; Plodkowski, Raymond; Greenway, Frank; Bays, Harold; Burns, Colleen; Klassen, Preston; Fujioka, Ken

    2013-12-01

    To assess the efficacy and safety of 32 mg naltrexone sustained-release (SR)/360 mg bupropion SR (NB) in overweight/obese individuals with type 2 diabetes with or without background oral antidiabetes drugs. This was a 56-week, double-blind, placebo-controlled study in which 505 patients received standardized lifestyle intervention and were randomized 2:1 to NB or placebo. Coprimary end points were percent weight change and achievement of ≥5% weight loss. Secondary end points included achievement of HbA1c blood glucose, and lipids. In the modified intent-to-treat population (54% female, 80% Caucasian, and mean age 54 years, weight 106 kg, BMI 37 kg/m(2), and HbA1c 8.0% [64 mmol/mol]), NB resulted in significantly greater weight reduction (-5.0 vs. -1.8%; P select cardiovascular risk factors and was generally well tolerated with a safety profile similar to that in patients without diabetes.

  16. Preparation and characterization of genipin-cross-linked silk fibroin/chitosan sustained-release microspheres

    Directory of Open Access Journals (Sweden)

    Zeng SG

    2015-05-01

    Full Text Available Shuguang Zeng,1,* Manwen Ye,1,2,* Junqi Qiu,1 Wei Fang,1 Mingdeng Rong,1 Zehong Guo,1 Wenfen Gao11Department of Oral and Maxillofacial Surgery, Guangdong Provincial Stomatological Hospital, Southern Medical University, 2Department of Stomatology, Guangdong Women and Children Hospital, Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of China*These authors contributed equally to this workAbstract: We report the effects of distinct concentrations of genipin and silk fibroin (SF:chitosan (CS ratios on the formation of SF–CS composite microspheres. We selected microspheres featuring an SF:CS ratio of 1:1, encapsulated various concentrations of bovine serum albumin (BSA, and then compared their encapsulation efficiency and sustained-release rate with those of pure CS microspheres. We determined that the following five groups of microspheres were highly spherical and featured particle sizes ranging from 70 µm to 147 µm: mass ratio of CS:SF =1:0.5, 0.1 g or 0.5 g genipin; CS:SF =1:1, 0.05 g or 1 g genipin; and CS:SF =1:2, 0.5 g genipin. The microspheres prepared using 1:1 CS:SF ratio and 0.05 g genipin in the presence of 10 mg, 20 mg, and 50 mg of BSA exhibited encapsulation efficiencies of 50.16%±4.32%, 56.58%±3.58%, and 42.19%±7.47%, respectively. Fourier-transform infrared spectroscopy (FTIR results showed that SF and CS were cross-linked and that the α-helices and random coils of SF were converted into β-sheets. BSA did not chemically react with CS or SF. Moreover, thermal gravimetric analysis (TGA results showed that the melting point of BSA did not change, which confirmed the FTIR results, and X-ray diffraction results showed that BSA was entrapped in microspheres in a noncrystalline form, which further verified the TGA and FTIR data. The sustained-release microspheres prepared in the presence of 10 mg, 20 mg, and 50 mg of BSA burst release 30.79%±3.43%, 34.41%±4.46%, and 41.75%±0.96% of the

  17. Novel Injectable Pentablock Copolymer Based Thermoresponsive Hydrogels for Sustained Release Vaccines.

    Science.gov (United States)

    Bobbala, Sharan; Tamboli, Viral; McDowell, Arlene; Mitra, Ashim K; Hook, Sarah

    2016-01-01

    The need for multiple vaccinations to enhance the immunogenicity of subunit vaccines may be reduced by delivering the vaccine over an extended period of time. Here, we report two novel injectable pentablock copolymer based thermoresponsive hydrogels made of polyethyleneglycol-polycaprolactone-polylactide-polycaprolactone-polyethyleneglycol (PEG-PCL-PLA-PCL-PEG) with varying ratios of polycaprolactone (PCL) and polylactide (PLA), as single shot sustained release vaccines. Pentablock copolymer hydrogels were loaded with vaccine-encapsulated poly lactic-co-glycolic acid nanoparticles (PLGA-NP) or with the soluble vaccine components. Incorporation of PLGA-NP into the thermoresponsive hydrogels increased the complex viscosity of the gels, lowered the gelation temperature, and minimized the burst release of antigen and adjuvants. The two pentablock hydrogels stimulated both cellular and humoral responses. The addition of PLGA-NP to the hydrogels sustained immune responses for up to 49 days. The polymer with a higher ratio of PCL to PLA formed a more rigid gel, induced stronger immune responses, and stimulated effective anti-tumor responses in a prophylactic melanoma tumor model.

  18. Sustained Release of Prindopril Erbumine from Its Chitosan-Coated Magnetic Nanoparticles for Biomedical Applications

    Directory of Open Access Journals (Sweden)

    Dena Dorniani

    2013-12-01

    Full Text Available The preparation of magnetic nanoparticles coated with chitosan-prindopril erbumine was accomplished and confirmed by X-ray diffraction, TEM, magnetic measurements, thermal analysis and infrared spectroscopic studies. X-ray diffraction and TEM results demonstrated that the magnetic nanoparticles were pure iron oxide phase, having a spherical shape with a mean diameter of 6 nm, compared to 15 nm after coating with chitosan-prindopril erbumine (FCPE. Fourier transform infrared spectroscopy study shows that the coating of iron oxide nanoparticles takes place due to the presence of some bands that were emerging after the coating process, which belong to the prindopril erbumine (PE. The thermal stability of the PE in an FCPE nanocomposite was remarkably enhanced. The release study showed that around 89% of PE could be released within about 93 hours by a phosphate buffer solution at pH 7.4, which was found to be of sustained manner governed by first order kinetic. Compared to the control (untreated, cell viability study in 3T3 cells at 72 h post exposure to both the nanoparticles and the pure drug was found to be sustained above 80% using different doses.

  19. Poloxamer-hydroxyethyl cellulose-α-cyclodextrin supramolecular gels for sustained release of griseofulvin.

    Science.gov (United States)

    Marcos, Xelhua; Pérez-Casas, Silvia; Llovo, José; Concheiro, Angel; Alvarez-Lorenzo, Carmen

    2016-03-16

    Supramolecular gels of poloxamer-hydroxyethyl cellulose (HEC)-α-cyclodextrin (αCD) were developed aiming to obtain synergisms regarding solubilization and sustained release of griseofulvin for topical application. The effects of αCD concentration (0-10%w/w) on the phase behavior of aqueous dispersions of Pluronic(®) P123 (14%w/w) mixed with HEC (2%w/w) were evaluated at 4, 20 and 37°C. The cooperative effects of the inclusion complex formation between poly(ethylene oxide) (PEO) blocks and HEC with αCD prevented phase separation and led to supramolecular networks that solubilize the antifungal drug. Rheological and bioadhesive properties of gels with and without griseofulvin could be easily tuned modulating the polymers proportions. Supramolecular gels underwent sol-gel transition at lower temperature than P123 solely dispersions and enabled drug sustained release for at least three weeks. All gels demonstrated good biocompatibility in the HET-CAM test. Furthermore, the drug-loaded gels showed activity against Trichophyton rubrum and Trichophyton mentagrophytes and thus may be useful for the treatment of tinea capitis and other cutaneous fungal infections. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. A dual strategy to improve psychotic patients’ compliance using sustained release quetiapine oral disintegrating tablets

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    Refaat Ahmed

    2016-12-01

    Full Text Available Quetiapine (QT is a short acting atypical antipsychotic drug effective in schizophrenia and bipolar disorder. This study aims at designing a novel dosage form of sustained release taste-masked QT orally disintegrating tablets (ODTs based on solid lipid micro-pellets (SLMPs. QT SLMPs were prepared using the hot melt extrusion technique and utilizing three lipid carriers: Compritol, Precirol and white beeswax either alone or in mixtures. They showed sustained QT release and a taste masking effect. The selected QT SLMP was further blended with an aqueous solution containing polyvinylpyrollidone (2.5 %, croscarmellose sodium (2 % and mannitol (50 %; it was then lyophilized into ODT in a mass ratio of 1:2, respectively. ODTs containing QT SLMPs showed: average wetting time (40.92 s, average oral disintegration time (21.49 s, average hardness (16.85 N and also imparted suitable viscosity to suspend pellets during the lyophilization process. In conclusion, lyophilization is a promising technique for the formulation of multiparticulate systems into ODTs.

  1. A dual strategy to improve psychotic patients' compliance using sustained release quetiapine oral disintegrating tablets.

    Science.gov (United States)

    Refaat, Ahmed; Sokar, Magda; Ismail, Fatma; Boraei, Nabila

    2016-12-01

    Quetiapine (QT) is a short acting atypical antipsychotic drug effective in schizophrenia and bipolar disorder. This study aims at designing a novel dosage form of sustained release taste-masked QT orally disintegrating tablets (ODTs) based on solid lipid micro-pellets (SLMPs). QT SLMPs were prepared using the hot melt extrusion technique and utilizing three lipid carriers: Compritol, Precirol and white beeswax either alone or in mixtures. They showed sustained QT release and a taste masking effect. The selected QT SLMP was further blended with an aqueous solution containing polyvinylpyrollidone (2.5 %), croscarmellose sodium (2 %) and mannitol (50 %); it was then lyophilized into ODT in a mass ratio of 1:2, respectively. ODTs containing QT SLMPs showed: average wetting time (40.92 s), average oral disintegration time (21.49 s), average hardness (16.85 N) and also imparted suitable viscosity to suspend pellets during the lyophilization process. In conclusion, lyophilization is a promising technique for the formulation of multiparticulate systems into ODTs.

  2. Higher quality quercetin sustained release ethyl cellulose nanofibers fabricated using a spinneret with a Teflon nozzle.

    Science.gov (United States)

    Li, Chen; Wang, Zhuan-Hua; Yu, Deng-Guang

    2014-02-01

    This study investigates the usage of a spinneret with a Teflon nozzle for fabrication of higher quality drug sustained-release electrospun nanofibers. Ethyl cellulose (EC) and quercetin were used as a filament-forming polymer matrix and an active pharmaceutical ingredient, respectively. The electrospinning was conducted using both a traditional stainless steel spinneret and a spinneret with a Teflon nozzle. Experimental results demonstrated that a Teflon-fluid interface at the spinneret's nozzle provided a better performance for implementing electrospinning than a traditional metal-fluid interface in the following aspects: (1) keeping more electrical energy on the working fluids for an efficacious process; (2) exerting less negative effect on the fluid to draw it back to the tube; and (3) making less possibility of clogging. The resulted nanofibers from the spinneret with a Teflon nozzle exhibited higher quality than those from the traditional spinneret in those: (1) smaller diameter and narrower distribution, 520±70 nm for the former and 750±280 nm for the later, as indicated by the field emission scanning electron microscopic images; and (2) better sustained-release profiles of quercetin from the former than the latter, as demonstrated by the in vitro dissolution tests. The new protocols about usage of Teflon as a spinneret's nozzle and the related knowledge disclosed here should promote the preparation and application of electrospun functional nanofibers. Copyright © 2013 Elsevier B.V. All rights reserved.

  3. Design of sustained-release nitrendipine microspheres having solid dispersion structure by quasi-emulsion solvent diffusion method

    DEFF Research Database (Denmark)

    Cui, Fude; Yang, Mingshi; Jiang, Yanyan

    2003-01-01

    that the particle size of microspheres was determined mainly by the agitation speed. The dissolution rate of nitrendipine from microspheres was enhanced significantly with increasing the amount of dispersing agents, and sustained by adding retarding agents. The release rate of microspheres could be controlled...... as amorphous state. The release profiles and content of the microspheres stored at a temperature of 40 degrees C and a relative humidity of 75% were unchanged during 3 months of accelerating condition of storage. And the relative bioavailability of the sustained-release microspheres compared with the Baypress...

  4. Gastro-floating bilayer tablets for the sustained release of metformin and immediate release of pioglitazone: preparation and in vitro/in vivo evaluation.

    Science.gov (United States)

    He, Wei; Li, Yongji; Zhang, Rao; Wu, Zhannan; Yin, Lifang

    2014-12-10

    Owing to the complementary mechanisms of action of metformin hydrochloride (MH) and pioglitazone hydrochloride (PG), combination therapy for type 2 diabetes mellitus using the two drugs is highly desired; on the other hand, MH is not well absorbed in lower gastrointestinal tract and has a short half-life, therefore compromising the therapeutic effects. Herein, the present study was to develop gastro-floating bilayer matrix tablets in which the two drugs were incorporated into two separate layers, aiming at sustaining MH release with enhanced absorption and achieving immediate release of PG. The tablets of the optimized formulation floated on the test medium for more than 24 h with 5 min of floating lag time, and sustained MH release for 12 h via a diffusion-dependent manner; and complete release of PG within 5 min were achieved. Moreover, a steady plasma concentration of MH with a 1.5-fold increase in bioavailability, decreased C(max) and reduced T(max) was obtained, and the in vivo behavior of PG was similar to the marked product. Summarily, sustained MH release with improved absorption and immediate release of PG were obtained simultaneously using the gastro-floating bilayer tablet, allowing strengthened combination therapy for diabetes mellitus. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. Sustained release donepezil loaded PLGA microspheres for injection: Preparation, in vitro and in vivo study

    Directory of Open Access Journals (Sweden)

    Wenjia Guo

    2015-10-01

    Full Text Available The purpose of this study was to develop a PLGA microspheres-based donepezil (DP formulation which was expected to sustain release of DP for one week with high encapsulation efficiency (EE. DP derived from donepezil hydrochloride was encapsulated in PLGA microspheres by the O/W emulsion-solvent evaporation method. The optimized formulation which avoided the crushing of microspheres during the preparation process was characterized in terms of particle size, morphology, drug loading and EE, physical state of DP in the matrix and in vitro and in vivo release behavior. DP microspheres were prepared successfully with average diameter of 30 µm, drug loading of 15.92 ± 0.31% and EE up to 78.79 ± 2.56%. Scanning electron microscope image showed it has integrated spherical shape with no drug crystal and porous on its surface. Differential scanning calorimetry and X-ray diffraction results suggested DP was in amorphous state or molecularly dispersed in microspheres. The Tg of PLGA was increased with the addition of DP. The release profile in vitro was characterized with slow but continuous release that lasted for about one week and fitted well with first-order model, which suggested the diffusion governing release mechanism. After single-dose administration of DP microspheres via subcutaneous injection in rats, the plasma concentration of DP reached peak concentration at 0.50 d, and then declined gradually, but was still detectable at 15 d. A good correlation between in vitro and in vivo data was obtained. The results suggest the potential use of DP microspheres for treatment of Alzheimer's disease over long periods.

  6. Pharmacokinetics of diltiazem hydrochloride delay-onset sustained-release pellet capsules in healthy volunteers

    Directory of Open Access Journals (Sweden)

    Xi-Qing Yan

    2013-03-01

    Full Text Available The pharmacokinetics (PK of ordinary tablets and sustained release capsules of diltiazem hydrochloride in human clinical trials had been studied. The PK of diltiazem hydrochloride delay-onset sustained-release pellet capsules, a new dosage form, has not been reported, although it is very important to clinical use. In this paper, we investigated the PK of diltiazem hydrochloride delay-onset sustained-release pellet capsules and the food influence in Chinese healthy volunteers. The PK parameters indicated that the diltiazem hydrochloride delay-onset sustained-release pellet capsules appeared marked characteristics of delayed and controlled release. An opened-label, randomized and parallel clinical trial was conducted in 36 Chinese healthy volunteers with single oral dose (90 mg, 180 mg or 270 mg and a multiple oral dose (90 mg d-1×6 d administration. The effect of food on the PK of one single oral dose (360 mg was investigated in 24 healthy Chinese volunteers. Plasma diltiazem concentration was determined by reversed-phase high-performance liquid chromatography (RP-HPLC and the main pharmacokinetic parameters were analyzed by PKSolver (Ver 2.0. All clinical studies were conducted in the Clinical Pharmacological Center (No. JDX1999064 of Xiangya Hospital Affiliated Central South University, China. The PK parameters suggested that the new formulation had marked characteristics of delayed and controlled release of diltiazem, and food intake did not alter significantly diltiazem pharmacokinetic parameters.Embora a farmacocinética (PK do cloridrato de diltiazem nas formas de comprimidos de liberação imediata e cápsulas de liberação modificada em ensaios clínicos já tenha sido relatada, a pesquisa da PK do cloridrato de diltiazem na forma de cápsulas com peletes de liberação retardada e sustentada ainda é muito importante. Neste trabalho, propusemos avaliar a farmacocinética do cloridrato de diltiazem administrado através desta nova forma

  7. Improved Mechanical Properties and Sustained Release Behavior of Cationic Cellulose Nanocrystals Reinforeced Cationic Cellulose Injectable Hydrogels.

    Science.gov (United States)

    You, Jun; Cao, Jinfeng; Zhao, Yanteng; Zhang, Lina; Zhou, Jinping; Chen, Yun

    2016-09-12

    Polysaccharide-based injectable hydrogels have several advantages in the context of biomedical use. However, the main obstruction associated with the utilization of these hydrogels in clinical application is their poor mechanical properties. Herein, we describe in situ gelling of nanocomposite hydrogels based on quaternized cellulose (QC) and rigid rod-like cationic cellulose nanocrystals (CCNCs), which can overcome this challenge. In all cases, gelation immediately occurred with an increase of temperature, and the CCNCs were evenly distributed throughout the hydrogels. The nanocomposite hydrogels exhibited increasing orders-of-magnitude in the mechanical strength, high extension in degradation and the sustained release time, because of the strong interaction between CCNCs and QC chains mediated by the cross-linking agent (β-glycerophosphate, β-GP). The results of the in vitro toxicity and in vivo biocompatibility tests revealed that the hydrogels did not show obvious cytotoxicity and inflammatory reaction to cells and tissue. Moreover, DOX-encapsulated hydrogels were injected beside the tumors of mice bearing liver cancer xenografts to assess the potential utility as localized and sustained drug delivery depot systems for anticancer therapy. The results suggested that the QC/CCNC/β-GP nanocomposite hydrogels had great potential for application in subcutaneous and sustained delivery of anticancer drug to increase therapeutic efficacy and improve patient compliance.

  8. Evaluation of gum mastic (Pistacia lentiscus as a microencapsulating and matrix forming material for sustained drug release

    Directory of Open Access Journals (Sweden)

    Dinesh M. Morkhade

    2017-09-01

    Full Text Available In this study, a natural gum mastic was evaluated as a microencapsulating and matrix-forming material for sustained drug release. Mastic was characterized for its physicochemical properties. Microparticles were prepared by oil-in-oil solvent evaporation method. Matrix tablets were prepared by wet and melt granulation techniques. Diclofenac sodium (DFS and diltiazem hydrochloride (DLTZ were used as model drugs. Mastic produced discrete and spherical microspheres with DLTZ and microcapsules with DFS. Particle size and drug loading of microparticles was in the range of 22–62 µm and 50–87%, respectively. Increase in mastic: drug ratio increased microparticle size, improved drug loading and decreased the drug release rate. Microparticles with gum: drug ratio of 2:1 could sustain DLTZ release up to 12 h and released 57% DFS in 12 h. Mastic produced tablets with acceptable pharmacotechnical properties. A 30% w/w of mastic in tablet could sustain DLTZ release for 5 h from wet granulation, and DFS release for 8 h and 11 h from wet and melt granulation, respectively. Results revealed that a natural gum mastic can be used successfully to formulate matrix tablets and microparticles for sustained drug release.

  9. HPLC determination and steady-state bioavailability study of levodropropizine sustained-release tablets in dogs.

    Science.gov (United States)

    Yan, Lin; Li, Tongling; Zhang, Rongqin; Xu, Xiaohong; Zheng, Pengcheng

    2006-06-01

    A simple HPLC method using UV detection was developed and validated for the determination of levodropropizine (LDP) in dog plasma. The sample was prepared for injection using a liquid-liquid extraction method with 1-phenypiperazine as the internal standard. The mobile phase was methanol-diethylamine solution (0.05 M) (20:80, v/v, pH adjusted to 3.0 with H3PO4) with a detection wavelength of 240 nm. The limit of quantitation (LOQ) of LDP in a biological matrix was determined to be 25.25 ng/mL. The calibration curve was linear across the concentration range of 25.25 to 2020 ng/mL. The intra-day and inter-day precision values (CV %) were within 7% and accuracy (R.E. %) was within 6% of the nominal values for medium (252.5 ng/mL) and high (2020 ng/mL) LDP concentrations. For the LDP concentration at the LOQ, the intra-day and inter-day precision and accuracy were within 20% and 10%, respectively. The average absolute recovery for LDP was 70.28%. This method was successfully used to analyze plasma samples in a steady-state bioavailability study of a newly developed sustained-release LDP tablets (SR) using immediate-release tablets (IR) as the reference. The relative bioavailability of the SR was determined to be 106.3 +/- 12.8% (n=6). The Cmax of the SR was significantly lower (P<0.05), and the tmax was significantly longer than that of the IR (P<0.05). The results of ANOVA and two one-sided tests indicated that the SR exhibited acceptable sustained release properties and was bioequivalent to the IR.

  10. Clinical Assessment of Urinary Tract Damage during Sustained-Release Estrogen Supplementation in Mice.

    Science.gov (United States)

    Collins, Dalis E; Mulka, Kathleen R; Hoenerhoff, Mark J; Taichman, Russell S; Villano, Jason S

    2017-02-01

    Estrogen supplementation is a key component of numerous mouse research models but can adversely affect the urinary system. The goal of this study was to develop a clinical scoring system and identify biomarkers of occult urinary tract lesions prior to the development of systemic illness in mice. Ovariectomized or sham-surgery SCID mice were implanted subcutaneously with a placebo pellet or one containing sustained-release estradiol (0.18 mg 60-d release 17β-estradiol). Mice were assessed twice weekly for 4 to 6 wk by using a clinical scoring system that included body condition, general activity, posture, hair coat, hydration, abdominal distension, urine staining of coat and skin, and ability to urinate. Samples were collected weekly for urinalysis, BUN, creatinine, and serum estradiol levels. Terminal samples were analyzed for histopathologic lesions. Compared with placebo controls, estradiolsupplemented mice had higher serum estradiol levels at weeks 2 and 3; significant differences in total clinical scores by the 3-wk time point; and in body condition, general activity, posture, hair coat, and urine staining scores by the 6-wk terminal time point. Urinary tract lesions included hydronephrosis, pyelonephritis, cystitis, and urolithiasis. All mice with urolithiasis had crystalluria, and 5 of the 6 mice with pyelonephritis or hydroureter had dilute urine (that is, specific gravity less than 1.030). However, these findings were not specific to mice with lesions. A total clinical score of 3.5 (maximum, 24) identified estradiol-supplemented mice with 83% specificity and 50% sensitivity, but no single clinical parameter, biomarker, or the total clinical score accurately predicted occult urinary tract lesions. Considering the lesions we observed, prudence is warranted when using pelleted sustained-release estradiol in mice, and important parameters to monitor for animal health include urine staining, body condition score, urine sediment, and urine specific gravity.

  11. The preparation of the sustained release metformin hydrochloride microcapsules by the Wurster fluidized bed.

    Science.gov (United States)

    Cao, Jin; Liu, Hongfei; Pan, Weisan; Sun, Changshan; Feng, Yingshu; Zhong, Hui; Shi, Shuang Shuang; He, Yan

    2014-07-01

    The main objective of this study was to prepare sustained release metformin hydrochloride microcapsules by the Wurster fluidized bed and to obtain the optimized coating process and formulation. Fine microcapsules without agglomeration were obtained in a continuous coating process with the atomization air pressure of 0.2Mpa and an appropriate coating speed temperature. With other design variables of coating process fixed, the effects of different fluidizing air volume, coating temperature, coating speed, coating material, coating materials amount, plasticizer type and plasticizer amount on drug release were investigated respectively. Coating solution was achieved by dissolving EC45cps of 21 g, EC100cps of 7 g, DBS of 2.8 g and talcum powder of 8 g in ethanol to get a final volume of 500 ml. Particles of 150g along with 500mL coating solution would be fine. The results showed that with the air volume of 35 m3•h-1, coating temperature of 35o, coating speed of 6 mL•min-1 and proper amount of coating solution, fine microcapsules were obtained. The mean diameter of the microcapsules obtained eventually were 213 μm and the drug content were 23%, which was suitable for producing a suspension. Particle diameter distribution corresponded to the normal distribution and obviously prolonged drug-release was achieved.

  12. Formulation Design, Optimization and Pharmacodynamic Evaluation of Sustained Release Mucoadhesive Microcapsules of Venlafaxine HCl.

    Science.gov (United States)

    Swain, S; Behera, A; Dinda, S C; Patra, C N; Jammula, Sruti; Beg, S; Rao, M E B

    2014-07-01

    The objective of present research work was to design and characterize the venlafaxine HCl-loaded sodium alginate-based mucoadhesive microcapsules by ionic gelation technique using HPMC K100M as mucoadhesive polymer. The Placket-Burman Design was applied for preliminary screening of the formulations and systematic optimization by using Box-Behnken Design. The prepared microcapsules were characterized for drug content, entrapment efficiency, micromeritic properties, particle size, swelling index, mucoadhesive strength, in vitro drug release and in vivo antidepressant activity. FTIR and differential scanning calorimetry studies showed no incompatibility. Surface morphology studies revealed spherical nature of the prepared microcapsules. In vitro drug release studies revealed sustained release by diffusion mechanism. Further, the microcapsules were effective in reducing the depression induced by forced swimming test in Sprague-Dawley rats compared to the pure drug. The microcapsules were found to be stable under accelerated stability conditions, which suggest them as better alternative delivery systems for enhanced therapeutic efficacy of antidepressant drug, venlafaxine HCl.

  13. Water hyacinth: a possible alternative rate retarding natural polymer used in sustained release tablet design.

    Science.gov (United States)

    Khatun, Sabera; Sutradhar, Kumar B

    2014-01-01

    In recent years natural polymers have been widely used because of their effectiveness and availability over synthetic polymers. In this present investigation matrix tablets of Metformin hydrochloride were formulated using Water hyacinth powder and its rate retardant activity was studied. Tablets were prepared using wet granulation method with 8% starch as granulating agent and 5, 10, 15, 20, 25 and 30% of Water hyacinth powder to the drug. In preformulation study, angle of repose, Carr's Index and Hausner ratio were calculated. Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), and Scanning Electron Microscopy (SEM) studies were performed and no interactions were found between drug and excipients. Weight variation, friability, hardness, thickness, diameter, and in vitro release study were performed with the prepared matrix tablets. Dissolution studies were conducted using USP type II apparatus at a speed of 100 rpm at 37°C ± 0.5 temperature for 8 h. Though all the formulations comply with both BP and USP requirements, formulation F-1 (5% of Water hyacinth) was the best fitted formula. The drug release patterns were explained in different kinetic models such as Zero order, First order, Higuchi, Hixson Crowell, and Korsmeyer-Peppas equations. The current investigation implies that Water hyacinth has the potential to be used as a rate-retarding agent in sustained release drug formulations.

  14. Modified silicone elastomer vaginal gels for sustained release of antiretroviral HIV microbicides.

    Science.gov (United States)

    Forbes, Claire J; McCoy, Clare F; Murphy, Diarmaid J; Woolfson, A David; Moore, John P; Evans, Abbey; Shattock, Robin J; Malcolm, R Karl

    2014-05-01

    We previously reported nonaqueous silicone elastomer gels (SEGs) for sustained vaginal administration of the CCR5-targeted entry inhibitor maraviroc (MVC). Here, we describe chemically modified SEGs (h-SEGs) in which the hydrophobic cyclomethicone component was partially replaced with relatively hydrophilic silanol-terminated polydimethylsiloxanes (st-PDMS). MVC and emtricitabine (a nucleoside reverse transcriptase inhibitor), both currently under evaluation as topical microbicides to counter sexual transmission of human immunodeficiency virus type 1 (HIV-1), were used as model antiretroviral (ARV) drugs. Gel viscosity and in vitro ARV release were significantly influenced by st-PDMS molecular weight and concentration in the h-SEGs. Unexpectedly, gels prepared with lower molecular weight grades of st-PDMS showed higher viscosities. h-SEGs provided enhanced release over 24 h compared with aqueous hydroxyethylcellulose (HEC) gels, did not modify the pH of simulated vaginal fluid (SVF), and were shown to less cytotoxic than standard HEC vaginal gel. ARV solubility increased as st-PDMS molecular weight decreased (i.e., as percentage hydroxyl content increased), helping to explain the in vitro release trends. Dye ingression and SVF dilution studies confirmed the increased hydrophilicity of the h-SEGs. h-SEGs have potential for use in vaginal drug delivery, particularly for ARV-based HIV-1 microbicides. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

  15. WATER HYACINTH: A POSSIBLE ALTERNATIVE RATE RETARDING NATURAL POLYMER USED IN SUSTAINED RELEASE TABLET DESIGN

    Directory of Open Access Journals (Sweden)

    Sabera eKhatun

    2014-06-01

    Full Text Available In recent years natural polymers have been widely used, because of their effectiveness and availability over synthetic polymers. In this present investigation matrix tablets of Metformin hydrochloride were formulated using Water hyacinth powder and its rate retardant activity was studied. Tablets were prepared using wet granulation method with 8% starch as granulating agent and 5%, 10%, 15%, 20%, 25% and 30% of Water hyacinth powder to the drug. In preformulation study, angle of repose, Carr’s Index and Hausner ratio were calculated. Fourier Transform Infrared Spectroscopy (FTIR, Differential Scanning Calorimetry (DSC and Scanning Electron Microscopy (SEM studies were performed and no interactions were found between drug and excipients. Weight variation, friability, hardness, thickness, diameter, and in vitro release study were performed with the prepared matrix tablets. Dissolution studies were conducted using USP type II apparatus at a speed of 100 rpm at 37oC ± 0.5 temperature, for 8 hours. All the formulations comply with both BP and USP requirements, but among all the formulations F-1 (5% of Water hyacinth was the best fitted formula. The drug release patterns were explained in different kinetic models such as Zero order, First order, Higuchi, Hixson Crowell and Korsmeyer-Peppas equations. The current investigation implies that Water hyacinth has the potential to be used as a rate-retarding agent in sustained release drug formulations.

  16. Injectable Chitosan/β-Glycerophosphate System for Sustained Release: Gelation Study, Structural Investigation, and Erosion Tests.

    Science.gov (United States)

    Dalmoro, Annalisa; Abrami, Michela; Galzerano, Barbara; Bochicchio, Sabrina; Barba, Anna Angela; Grassi, Mario; Larobina, Domenico

    2017-01-01

    Hydrogels can constitute reliable delivery systems of drugs, including those based on nucleic acids (NABDs) such as small interfering ribonucleic acid (siRNA). Their nature, structure, and response to physiological or external stimuli strongly influence the delivery mechanisms of entrapped active molecules, and, in turn, their possible uses in pharmacological and biomedical applications. In this study, a thermo-gelling chitosan/β-glycero-phosphate system has been optimized in order to assess its use as injectable system able to: i) gelling at physiological pH and temperature, and ii) modulate the release of included active ingredients. To this aim, we first analyzed the effect of acetic acid concentration on the gelation temperature. We then found the "optimized composition", namely, the one in which the Tgel is equal to the physiological temperature. The resulting gel was tested, by low field nuclear magnetic resonance (LF-NMR), to evaluate its average mesh-size, which can affect release kinetics of loaded drug. Finally, films of gelled chitosan, loaded with a model drug, have been tested in vitro to monitor their characteristic times, i.e. diffusion and erosion time, when they are exposed to a medium mimicking a physiological environment (buffer solution at pH 7.4). Results display that the optimized system is deemed to be an ideal candidate as injectable gelling material for a sustained release. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  17. IPX066 , a mixed immediate/sustained-release levodopa preparation for Parkinson's disease.

    Science.gov (United States)

    Ondo, William

    2014-10-01

    L-DOPA has long been the 'gold standard' treatment for Parkinson's disease (PD), but suffers from poor oral bioavailability and rapid pharmacokinetic elimination. A longer acting preparation has long been sought. We conducted PubMed search for IPX066 and reviewed abstracts from meetings that included the topic of PD. IPX066 is a novel mixed immediate release (IR) and sustained-release levodopa preparation designed to prolong the clinical effect of a single dose. Pharmacokinetic studies demonstrate similar time to peak dose as regular IR L-DOPA, but a longer duration of time with > 50% of peak dose. This contrasts with available controlled release preparations that have a delay to onset. Clinic trials in fluctuating PD patients show that IPX066 provided more 'on' time despite fewer daily doses, compared to IR L-DOPA. As expected, it was also superior to placebo in early PD. However, it is not known whether it can achieve l-DOPA levels that are continuous enough to delay the onset of fluctuations when given early in the disease. Although not a radical advance in L-DOPA therapy, the drug will clearly have a role in more advanced patients taking multiple L-DOPA doses and may have a role as first-line therapy when starting l-DOPA.

  18. Modified silicone elastomer vaginal gels for sustained release of antiretroviral HIV microbicides

    Science.gov (United States)

    Forbes, Claire J.; McCoy, Clare F.; Murphy, Diarmaid J.; Woolfson, A. David; Moore, John P.; Evans, Abbey; Shattock, Robin J.; Malcolm, R. Karl

    2014-01-01

    We previously reported non-aqueous silicone elastomer gels (SEGs) for sustained vaginal administration of the CCR5-targeted entry inhibitor maraviroc. Here, we describe chemically modified SEGs (h-SEGs) in which the hydrophobic cyclomethicone component was partially replaced with relatively hydrophilic silanol-terminated polydimethylsiloxanes (st-PDMS). Maraviroc and emtricitabine (a nucleoside reverse transcriptase inhibitor), both currently under evaluation as topical microbicides to counter sexual transmission of human immunodeficiency virus type 1 (HIV-1), were used as model antiretroviral (ARV) drugs. Gel viscosity and in vitro ARV release were significantly influenced by st-PDMS molecular weight and concentration in the h-SEGs. Unexpectedly, gels prepared with lower molecular weight grades of st-PDMS showed higher viscosities. h-SEGs provided enhanced release over 24 h compared with aqueous hydroxyethylcellulose (HEC) gels, did not modify the pH of simulated vaginal fluid (SVF), and were shown to less cytotoxic than standard hydroxyethylcellulose (HEC) vaginal gel. ARV solubility increased as st-PDMS molecular weight decreased (i.e. as percentage hydroxyl content increased), helping to explain the in vitro release trends. Dye ingression and SVF dilution studies confirmed the increased hydrophilicity of the h-SEGs. h-SEGs have potential for use in vaginal drug delivery, particularly for ARV-based HIV-1 microbicides. PMID:24585370

  19. Chlorogenic acid loaded chitosan nanoparticles with sustained release property, retained antioxidant activity and enhanced bioavailability

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    Ilaiyaraja Nallamuthu

    2015-06-01

    Full Text Available In this study, chlorogenic acid (CGA, a phenolic compound widely distributed in fruits and vegetables, was encapsulated into chitosan nanoparticles by ionic gelation method. The particles exhibited the size and zeta potential of 210 nm and 33 mV respectively. A regular, spherical shaped distribution of nanoparticles was observed through scanning electron microscopy (SEM and the success of entrapment was confirmed by FTIR analysis. The encapsulation efficiency of CGA was at about 59% with the loading efficiency of 5.2%. In vitro ABTS assay indicated that the radical scavenging activity of CAG was retained in the nanostructure and further, the release kinetics study revealed the burst release of 69% CGA from nanoparticles at the end of 100th hours. Pharmacokinetic analysis in rats showed a lower level of Cmax, longer Tmax, longer MRT, larger AUC0–t and AUC0–∞ for the CGA nanoparticles compared to free CGA. Collectively, these results suggest that the synthesised nanoparticle with sustained release property can therefore ease the fortification of food-matrices targeted for health benefits through effective delivery of CGA in body.

  20. An epichlorohydrin-crosslinked semi-interpenetrating GG-PEO network as a xerogel matrix for sustained release of sulpiride.

    Science.gov (United States)

    Hoosain, Famida G; Choonara, Yahya E; Kumar, Pradeep; Tomar, Lomas K; Tyagi, Charu; du Toit, Lisa C; Pillay, Viness

    2014-10-01

    The current study involved the development of a novel sustained release crosslinked semi-IPN xerogel matrix tablet prepared by chemical crosslinking of poly(ethylene) oxide (PEO) and gellan gum (GG) employing epichlorohydrin (EPI) as crosslinker. A Box-Behnken design was employed for the statistical optimization of the matrix system to ascertain the ideal combination of native polymeric and crosslinking agents. Characterization studies were performed by employing standard polymer characterization techniques such as Fourier transform infrared spectrometry, differential scanning calorimetry, and scanning electron microscopy. Formulated matrix tablets displayed zero-order release kinetics, extending over 24 h. The mechanism of drug release was primarily by swelling and surface erosion. Crosslinked semi-IPN xerogel matrix tablets were compared to non-crosslinked polymer blends; results from the study conducted showed that the physiochemical properties of the PEO and GG were sufficiently modified to allow for sustained release of sulpiride with a 100% drug release at 24 h in a controlled manner as compared to non-crosslinked formulations which displayed further release beyond the test period. Crosslinked formulations displayed water uptake between 450 and 500% indicating a controlled rate of swelling and erosion allowing for sustained release. Surface morphology of the crosslinked system depicted a porous structure formed by interpenetrating networks of polymers, allowing for a greater degree of controlled penetration into the system affording it the ability to sustain drug release. Therefore, conclusively, based on the study performed, crosslinked PEO-GG allows for the sustained release of sulpiride from a hydrophilic semi-IPN xerogel matrix system.

  1. Effects of immediate-release opioid on memory functioning: a randomized-controlled study in patients receiving sustained-release opioids.

    Science.gov (United States)

    Kamboj, S K; Conroy, L; Tookman, A; Carroll, E; Jones, L; Curran, H V

    2014-11-01

    The effects of opioid medication on cognitive functioning in patients with cancer and non-cancer pain remain unclear. In this mechanistic randomized, double-blind, placebo-controlled, cross-over study of patients (n = 20) receiving sustained-release and immediate-release opioid medication as part of their palliative care, we examine memory effects of an additional dose of participants' immediate-release medication (oxycodone or morphine) or placebo. Immediate prose recall and recall of related and unrelated word pairs was assessed pre-and post-drug (placebo or immediate-release opioid). Memory for these stimuli was also tested after a delay on each testing occasion. Finally, performance on an 'interference' word pair task was assessed on the two testing occasions since proactive interference has been posited as a mechanism for acute opioid-induced memory impairment. Unlike previous work, we found no evidence of memory impairment for material presented before or after individually tailored, 'breakthrough' doses of immediate-release opioid. Furthermore, immediate-release opioid did not result in increased memory interference. On the other hand, we found enhanced performance on the interference word pair task after immediate-release opioid, possibly indicating lower levels of interference. These results suggest that carefully titrated immediate-release doses of opioid drugs may not cause extensive memory impairment as previously reported, and in fact, may improve memory in certain circumstances. Importantly, our findings contrast strikingly with those of a study using the same robust design that showed significant memory impairment. We propose that factors, such as depressive symptoms, education level and sustained-release opioid levels may influence whether impairment is observed following immediate-release opioid treatment. © 2014 European Pain Federation - EFIC®

  2. Development of Sustained Release "NanoFDC (Fixed Dose Combination" for Hypertension - An Experimental Study.

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    Anjuman Arora

    Full Text Available The present study was planned to formulate, characterize and evaluate the pharmacokinetics of a novel "NanoFDC" comprising three commonly prescribed anti-hypertensive drugs, hydrochlorothiazide (a diuretic, candesartan (ARB and amlodipine (a calcium channel blocker.The candidate drugs were loaded in Poly (DL-lactide-co-gycolide (PLGA by emulsion- diffusion-evaporation method. The formulations were evaluated for their size, morphology, drug loading and in vitro release individually. Single dose pharmacokinetic profiles of the nanoformulations alone and in combination, as a NanoFDC, were evaluated in Wistar rats.The candidate drugs encapsulated inside PLGA showed entrapment efficiencies ranging from 30%, 33.5% and 32% for hydrochlorothiazide, candesartan and amlodipine respectively. The nanoparticles ranged in size from 110 to 180 nm. In vitro release profile of the nanoformulation showed 100% release by day 6 in the physiological pH 7.4 set up with PBS (phosphate buffer saline and by day 4-5 in the intestinal pH 1.2 and 8.0 set up SGF (simulated gastric fluid and SIF (simulated intestinal fluid respectively. In pharmacokinetic analysis a sustained-release for 6 days and significant increase in the mean residence time (MRT, as compared to the respective free drugs was noted [MRT of amlodipine, hydrochlorothiazide and candesartan changed from 8.9 to 80.59 hours, 11 to 69.20 hours and 9 to 101.49 hours respectively].We have shown for the first time that encapsulating amlodipine, hydrochlorothiazide and candesartan into a single nanoformulation, to get the "NanoFDC (Fixed Dose Combination" is a feasible strategy which aims to decrease pill burden.

  3. Sustained-release genistein from nanostructured lipid carrier suppresses human lens epithelial cell growth

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    Jin-Lu Liu

    2016-05-01

    Full Text Available AIM: To design and investigate the efficacy of a modified nanostructured lipid carrier loaded with genistein (Gen-NLC to inhibit human lens epithelial cells (HLECs proliferation. METHODS: Gen-NLC was made by melt emulsification method. The morphology, particle size (PS, zeta potentials (ZP, encapsulation efficiency (EE and in vitro release were characterized. The inhibition effect of nanostructured lipid carrier (NLC, genistein (Gen and Gen-NLC on HLECs proliferation was evaluated by cell counting kit-8 (CCK-8 assay, gene and protein expression of the proliferation marker Ki67 were evaluated with real-time quantitative polymerase chain reaction (RT-qPCR and immunofluorescence analyses. RESULTS: The mean PS of Gen-NLC was 80.12±1.55 nm with a mean polydispersity index of 0.11±0.02. The mean ZP was -7.14±0.38 mV and the EE of Gen in the nanoparticles was 92.3%±0.73%. Transmission electron microscopy showed that Gen-NLC displayed spherical-shaped particles covered by an outer-layer structure. In vitro release experiments demonstrated a prolonged drug release for 72h. The CCK-8 assay results showed the NLC had no inhibitory effect on HLECs and Gen-NLC displayed a much more prominent inhibitory effect on cellular growth compared to Gen of the same concentration. The mRNA and protein expression of Ki67 in LECs decreased significantly in Gen-NLC group. CONCLUSION: Sustained drug release by Gen-NLCs may impede HLEC growth.

  4. Formulating nanoparticles by flash nanoprecipitation for drug delivery and sustained release

    Science.gov (United States)

    Liu, Ying

    This dissertation provides a fundamental understanding of the process for generating nanoparticles with controlled size distribution and of predicting nanoparticle stability for drug delivery and sustained release. We developed and characterized a novel technology to generate organic and inorganic nanoparticles protected by biocompatible and biodegradable polymers with precisely controlled size and size distribution. Computational fluid mechanics (CFD) together with experimental results provided details of the micromixing in the mixer. The particle size dependence on Reynolds number and supersaturation was illustrated. The study of the fundamental mass transfer phenomena leading to Ostwald ripening enables quantitative prediction of the time evolution of nanoparticles with monodistribution and relatively broader multi-distribution using beta-carotene and polystyrene-b-poly(ethylene oxide) (PS-b-PEO) as a model system. Negatively charged latex particles were used to exam the attachment of the diblock copolymer, PS-b-PEO, on the surface. The stability provided by the Columbic repulsion was replaced by steric stabilization. The attachment of the block copolymers on the surface of the colloids depends on the flow field, i.e. Reynolds number, of the mixing process. The slow degradation of poly(epsilon-caprolactone) (PCL) and poly(gamma-methyl-epsilon-caprolactone) (PMCL) was demonstrated. The slow degradation ensures long-term stability and long-term blood circulation of the polymeric nanoparticles. As a practical application, we formulate the anti-tuberculosis drug, rifampicin, into nanoparticles by conjugation to other hydrophobic molecules (such as vitamin E, PCL and 2-ethylhexyl vinyl ether) by pH sensitive cleavable chemical bonds to increase the drug loading, return stability of the nanoparticle suspension, and control drug release. The in vitro release profiles were provided by using HPLC and E.coli growth inhibition on LB agar plates. The prodrug nanoparticle

  5. The Stability, Sustained Release and Cellular Antioxidant Activity of Curcumin Nanoliposomes

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    Xing Chen

    2015-08-01

    Full Text Available Curcumin is a multifunctional and natural agent considered to be pharmacologically safe. However, its application in the food and medical industry is greatly limited by its poor water solubility, physicochemical instability and inadequate bioavailability. Nanoliposome encapsulation could significantly enhance the solubility and stability of curcumin. Curcumin nanoliposomes exhibited good physicochemical properties (entrapment efficiency = 57.1, particle size = 68.1 nm, polydispersity index = 0.246, and zeta potential = −3.16 mV. Compared with free curcumin, curcumin nanoliposomes exhibited good stability against alkaline pH and metal ions as well as good storage stability at 4 °C. Curcumin nanoliposomes also showed good sustained release properties. Compared with free curcumin, curcumin nanoliposomes presented an equal cellular antioxidant activity, which is mainly attributed to its lower cellular uptake as detected by fluorescence microscopy and flow cytometry. This study provide theoretical and practical guides for the further application of curcumin nanoliposomes.

  6. The Stability, Sustained Release and Cellular Antioxidant Activity of Curcumin Nanoliposomes.

    Science.gov (United States)

    Chen, Xing; Zou, Li-Qiang; Niu, Jing; Liu, Wei; Peng, Sheng-Feng; Liu, Cheng-Mei

    2015-08-05

    Curcumin is a multifunctional and natural agent considered to be pharmacologically safe. However, its application in the food and medical industry is greatly limited by its poor water solubility, physicochemical instability and inadequate bioavailability. Nanoliposome encapsulation could significantly enhance the solubility and stability of curcumin. Curcumin nanoliposomes exhibited good physicochemical properties (entrapment efficiency = 57.1, particle size = 68.1 nm, polydispersity index = 0.246, and zeta potential = -3.16 mV). Compared with free curcumin, curcumin nanoliposomes exhibited good stability against alkaline pH and metal ions as well as good storage stability at 4 °C. Curcumin nanoliposomes also showed good sustained release properties. Compared with free curcumin, curcumin nanoliposomes presented an equal cellular antioxidant activity, which is mainly attributed to its lower cellular uptake as detected by fluorescence microscopy and flow cytometry. This study provide theoretical and practical guides for the further application of curcumin nanoliposomes.

  7. Evaluation of free and liposome-encapsulated gentamycin for intramuscular sustained release in rabbits.

    Science.gov (United States)

    Cabanes, A; Reig, F; Garcia-Anton, J M; Arboix, M

    1998-01-01

    Gentamycin sulphate (GS) and gentamycin oleate (GO) were encapsulated in liposomes composed of phosphatidylcholine (HPC) and cholesterol (CHOL) (molar ratio 7:7:2 and 5:5:1, respectively), and were administered via intramuscular injection to rabbits, to evaluate their potential use as sustained release formulations. Five groups of five animals each were used for the pharmacokinetic study, and treatments were established as follows: 3 mg kg(-1) of GS i.v., 3 mg kg(-1) of GS i.m., 3 mg kg(-1) of liposome-containing gentamycin sulphate (LGS) i.m., 3 mg kg(-1) of GO i.m., and 3 mg kg(-1) of liposome-containing gentamycin oleate (LGO) i.m. Gentamycin plasma concentrations after i.m. administration of LGS were extremely low compared with those obtained after the i.m. administration of GS; the peak plasma concentration (Cmax) showed an eight-fold decrease with LGS, and the area under the concentration-time curve (AUC) was four-fold lower for the liposomal form. The apparent elimination half-life estimated after administration of LGS showed a three-fold increase compared with values calculated for free GS. After the administration of the same dose of LGO, Cmax obtained showed a 2.5-fold decrease in relation to peak concentrations of free GO, and the apparent beta-half life of encapsulated GO showed a three-fold increase compared with i.m. GO. Large-size liposomes containing gentamycin administered i.m. to rabbits gave sustained drug release from the injection site, providing prolonged plasma concentrations of the drug in the body.

  8. Taste masking of azithromycin by resin complex and sustained release through interpenetrating polymer network with functionalized biopolymers.

    Science.gov (United States)

    Rajesh, A Michael; Popat, Kiritkumar Mangaldas

    2017-05-01

    The objective was to evaluate taste masking of azithromycin (AZI) by ion exchange resins (IERs) and the formation of covalent semi interpenetrating polymer network (IPN) beads using chitosan (CS) and sodium carboxylated agarose (SCAG) for sustained release of drug. Methacrylic acid (MAA)-based IERs were prepared by suspension polymerization method. Drug release complexes (DRCs) were prepared by different drug:resin ratios i.e. 1:1, 1:2 and 1:4. The resultant DRCs were characterized using DSC, FTIR, PXRD, in vivo and in vitro taste masking, and in vitro drug release at gastric pH. IPN beads were prepared by entrapping DRCs with bio polymers and cross linked with trisodium citrate (NaCIT), and further cross-linked with glutaraldehyde (GA) for sustained release of AZI. In vitro and in vivo taste masking studies showed that MD1:4 DRC formulation was optimal. The release of AZI from DRC was found to be very fast at gastric pH i.e. 97.37 ± 1.02% within 45 min. The formation of IPN beads was confirmed by FTIR. The release of drug from IPN beads at gastric and intestinal pH was found to be "taste masking and newly formulated IPN beads demonstrated sustained release of AZI.

  9. Relationship Between Drug Discrimination and Ratings of Subjective Effects: Implications for Assessing and Understanding the Abuse Potential of d-Amphetamine in Humans

    Science.gov (United States)

    Reynolds, Anna R.; Bolin, B. Levi; Stoops, William W.; Rush, Craig R.

    2014-01-01

    The discriminative and subjective effects of drugs in humans are related, but the full extent of this relationship remains to be determined. To further explore this relationship, a retrospective analysis was conducted on data from six studies completed in our laboratory that used identical procedures. The relationship between the discriminative and subjective effects of a range of doses of d-amphetamine (i.e., 2.5–15 mg) was examined using correlational analyses. Significant correlations with discrimination performance were observed on 15 of 20 items from the Drug-Effect Questionnaire across a range of qualities (e.g., Pay For [a positive effect indicative of abuse potential] and Active [a stimulant-like effect]), but the magnitude of these relationships was modest (r amphetamine and indicate that the former are a more practical means to assess abuse potential of drugs. Although these procedures are fundamentally related in that they rely on the presence of an interoceptive drug state, they differ in the dimension(s) of the interoceptive effects that participants must quantify. The simultaneous use of drug discrimination and subjective effects may, therefore, reveal complimentary aspects of drug effects that underlie their potential for abuse. PMID:23851485

  10. Controlled release for crop and wood protection: Recent progress toward sustainable and safe nanostructured biocidal systems.

    Science.gov (United States)

    Mattos, Bruno D; Tardy, Blaise L; Magalhães, Washington L E; Rojas, Orlando J

    2017-09-28

    We review biocide delivery systems (BDS), which are designed to deter or control harmful organisms that damage agricultural crops, forests and forest products. This is a timely topic, given the growing socio-economical concerns that have motivated major developments in sustainable BDS. Associated designs aim at improving or replacing traditional systems, which often consist of biocides with extreme behavior as far as their solubility in water. This includes those that compromise or pollute soil and water (highly soluble or volatile biocides) or those that present low bioavailability (poorly soluble biocides). Major breakthroughs are sought to mitigate or eliminate consequential environmental and health impacts in agriculture and silviculture. Here, we consider the most important BDS vehicles or carriers, their synthesis, the environmental impact of their constituents and interactions with the active components together with the factors that affect their rates of release such as environmental factors and interaction of BDS with the crops or forest products. We put in perspective the state-of-the-art nanostructured carriers for controlled release, which need to address many of the challenges that exist in the application of BDS. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Propolis Varnish: Antimicrobial Properties against Cariogenic Bacteria, Cytotoxicity, and Sustained-Release Profile

    Directory of Open Access Journals (Sweden)

    Mariana P. De Luca

    2014-01-01

    Full Text Available Varnishes are preparations that differ in the polymeric matrix and therapeutical agents. In dentistry they are used to prevent caries. In this study we developed a propolis varnish, considering propolis properties against cariogenic bacteria. To a chitosan polymeric base (CHV was added ethanolic propolis extract in different concentrations: PV1 (5%, PV2 (10%, and PV3 (15%. Antimicrobial activity was carried out against Streptococcus mutans (SM, Streptococcus sanguinis (SG, Streptococcus salivarius (SS, and Lactobacillus casei (LC through agar diffusion method. The three propolis concentrations incorporated were effective in inhibiting the growth of all microorganisms, but without significant difference between the zones of inhibition observed. Cytotoxicity assay was done by MTT method. Data were analyzed by one-way ANOVA and Bonferroni test. None of the varnishes were cytotoxic, keeping 80% of viable cells, while CHV allowed cellular proliferation (120%. Sustained-release test was carried out by applying 40 μL of each varnish in the buccal surface of bovine teeth and kept in an ethanol/water solution removed in regular times. According to the “independent model approach,” the release profiles were distinct from each varnish and the most prolonged was PV3 (8 weeks. Varnish formulations had satisfactory antimicrobial activity against cariogenic bacteria and have a low cytotoxicity (<50%.

  12. A Strategy to Develop Bioactive Nanoarchitecture Cellulose: Sustained Release and Multifarious Applications.

    Science.gov (United States)

    Karuppusamy, Sembanadar; Pratheepkumar, Annamalai; Dhandapani, Perumal; Maruthamuthu, Sundaram; Kulandainathan, Manickam Anbu

    2015-09-01

    Cellulose membranes were engineered to produce hydrophobic surfaces via a simple and soft chemical process to introduce multifunctional properties of an otherwise hydrophilic cellulose surface with polymer-grafted nanosilver to form a core-shell nanostructure. A superhydrophobic domain of the polymer on cellulose was created through the amide bond formation between the anhydride units of the polymer and the aminosiloxane-functionalized cellulose through layer-over-layer formulation. This formulation was confirmed through XPS, XRD, 29Si-NMR, and FTIR studies. Further, SEM and TEM analysis revealed that short linear silver nanowires were uniformly obtained with an average diameter of 60 nm and length of 288 nm, using a mild reducing agent at 60 degrees C, which resulted in a hierarchical cellulose surface. The nanosilver colloids released from the hierarchical cellulose surface were stabilized by the polymer matrix in solution, which led to a decrease in the rate of formation of Ag+ enhancing the material's killing efficacy against microbes. This biodegradable nanocomposite-based cellulose hierarchical surface development has potential for application as superhydrophobic membranes for oil-water separation, antimicrobial activity, and pH-triggered sustained release of colloidal silver for wound healing, which could possibly be applied for use as smart bandages.

  13. New Poly(3-hydroxybutyrate) Microparticles with Paclitaxel Sustained Release for Intraperitoneal Administration.

    Science.gov (United States)

    Bonartsev, Anton P; Zernov, Anton L; Yakovlev, Sergey G; Zharkova, Irina I; Myshkina, Vera L; Mahina, Tatiana K; Bonartseva, Garina A; Andronova, Natalia V; Smirnova, Galina B; Borisova, Juliya A; Kalishjan, Mikhail S; Shaitan, Konstantin V; Treshalina, Helena M

    2017-01-01

    Poly(hydroxyalkanoates) (PHA) have recently attracted increasing attention due to their biodegradability and high biocompatibility, which makes them suitable for the development of new prolong drug formulations. This study was conducted to develop new prolong paclitaxel (PTX) formulation based on poly(3- hydroxybutyrate) (PHB) microparticles. PHB microparticles loaded with antitumor cytostatic drug PTX were obtained by spray-drying method using Nano Spray Dryer B-90. The PTX release kinetics in vitro from PHB microparticles and their cytotoxity on murine hepatoma cell line MH-22a were studied. Microparticles antitumor activity in vivo was studied using intraperitoneally (i.p.) transplanted tumor models: murine Lewis lung carcinoma and xenografts of human breast cancer RMG1. Uniform PTX release from PHB-microparticles during 2 months was observed. PTX-loaded PHB microparticles have demonstrated a significant antitumor activity versus pure drug both in vitro in murine hepatoma cells and in vivo when administered i.p. to mice with murine Lewis lung carcinoma and xenografts of human breast cancer RMG1. The developed technique of PTX sustained delivery from PHB-microparticles has therapeutic potential as prolong anticancer drug formulation. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  14. Fabrication and evaluation of a sustained-release chitosan-based scaffold embedded with PLGA microspheres

    Energy Technology Data Exchange (ETDEWEB)

    Song, Kedong, E-mail: kedongsong@dlut.edu.cn [Dalian R and D Center for Stem Cell and Tissue Engineering, State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116024 (China); Liu, Yingchao [Dalian R and D Center for Stem Cell and Tissue Engineering, State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116024 (China); Macedo, Hugo M. [Biological Systems Engineering Laboratory, Department of Chemical Engineering, Department of Chemical Engineering, South Kensington Campus, London SW7 2AZ (United Kingdom); Jiang, Lili; Li, Chao; Mei, Guanyu [Dalian R and D Center for Stem Cell and Tissue Engineering, State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116024 (China); Liu, Tianqing, E-mail: liutq@dlut.edu.cn [Dalian R and D Center for Stem Cell and Tissue Engineering, State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116024 (China)

    2013-04-01

    Nutrient depletion within three-dimensional (3D) scaffolds is one of the major hurdles in the use of this technology to grow cells for applications in tissue engineering. In order to help in addressing it, we herein propose to use the controlled release of encapsulated nutrients within polymer microspheres into chitosan-based 3D scaffolds, wherein the microspheres are embedded. This method has allowed maintaining a stable concentration of nutrients within the scaffolds over the long term. The polymer microspheres were prepared using multiple emulsions (w/o/w), in which bovine serum albumin (BSA) and poly (lactic-co-glycolic) acid (PLGA) were regarded as the protein pattern and the exoperidium material, respectively. These were then mixed with a chitosan solution in order to form the scaffolds by cryo-desiccation. The release of BSA, entrapped within the embedded microspheres, was monitored with time using a BCA kit. The morphology and structure of the PLGA microspheres containing BSA before and after embedding within the scaffold were observed under a scanning electron microscope (SEM). These had a round shape with diameters in the range of 27–55 μm, whereas the chitosan-based scaffolds had a uniform porous structure with the microspheres uniformly dispersed within their 3D structure and without any morphological change. In addition, the porosity, water absorption and degradation rate at 37 °C in an aqueous environment of 1% chitosan-based scaffolds were (92.99 ± 2.51) %, (89.66 ± 0.66) % and (73.77 ± 3.21) %, respectively. The studies of BSA release from the embedded microspheres have shown a sustained and cumulative tendency with little initial burst, with (20.24 ± 0.83) % of the initial amount released after 168 h (an average rate of 0.12%/h). The protein concentration within the chitosan-based scaffolds after 168 h was found to be (11.44 ± 1.81) × 10{sup −2} mg/mL. This novel chitosan-based scaffold embedded with PLGA microspheres has proven to be a

  15. Modified thermoresponsive Poloxamer 407 and chitosan sol-gels as potential sustained-release vaccine delivery systems.

    Science.gov (United States)

    Kojarunchitt, Thunjiradasiree; Baldursdottir, Stefania; Dong, Yao-Da; Boyd, Ben J; Rades, Thomas; Hook, Sarah

    2015-01-01

    Thermoresponsive, particle-loaded, Poloxamer 407 (P407)-Pluronic-R® (25R4) or chitosan-methyl cellulose (MC) formulations were developed as single-dose, sustained release vaccines. The sol-gels, loaded either with a particulate vaccine (cubosomes) or soluble antigen (ovalbumin) and adjuvants (Quil A and monophosphoryl lipid A), were free-flowing liquids at room temperature and formed stable gels at physiological temperatures. Rheological results showed that both systems meet the criteria of being thermoresponsive gels. The P407-25R4 sol-gels did not significantly sustain the release of antigen in vivo while the chitosan-MC sol-gels sustained the release of antigen up to at least 14 days after administration. The chitosan-MC sol-gels stimulated both cellular and humoral responses. The inclusion of cubosomes in the sol-gels did not provide a definitive beneficial effect. Further analysis of the formulations with small-angle X-ray scattering (SAXS) revealed that while cubosomes were stable in chitosan-MC gels they were not stable in P407-25R4 formulations. The reason for the mixed response to cubosome-loaded vehicles requires more investigation, however it appears that the cubosomes did not facilitate synchronous vaccine release and may in fact retard release, reducing efficacy in some cases. From these results, chitosan-MC sol-gels show potential as sustained release vaccine delivery systems, as compared to the P407-25R4 system that had a limited ability to sustain antigen release. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. In Vitro – In Vivo Evaluation of SustainedRelease Lithium Carbonate Matrix Tablets: Influence of Hydrophilic Matrix Materials

    Directory of Open Access Journals (Sweden)

    J Emami

    2004-04-01

    Full Text Available Background: Conventional Lithium carbonate (LC tablets produce rapid and relatively high peak blood levels resulting in adverse effects. These drawbacks can be overcome by designing a suitable sustained or controlled-release LC preparation. Methods: Sustained-release matrix tablets were therefore developed using different types and ratios of polymers including carbomer (CP, Na carboxymethylcellulose (Na CMC and hydroxypropylmethylcellulose (HPMC, to assess the release profiles and in vivo performance of the formulations. The tablets were prepared by either direct compression (DC or wet granulation (WG. In the DC method, 69% (450 mg LC, 5, 10 or 15% CP or Na CMC (of total tablet weight, lactose and /or Avicel (to maintain constant tablet weight were mixed and directly compressed. In the WG method, 450 mg LC and 10, 20, or 30% HPMC were granulated with Eudragit S100 solution, dried, and then compressed to formulate the tablets. In vitro and in vivo, newly formulated sustained-release LC tablets were compared with sustained-release commercial tablets (Eskalith and Priadel. In vivo studies were conducted in nine healthy subjects in a cross-over design, with a 3x3 Latin square sequence, and pharmacokinetic parameters were estimated using classical methods. Results: The matrix tablets containing 15% CP exhibited suitable release kinetics and uniform absorption characteristics comparable to that of Eskalith. In vivo, this formulation produced a smooth and extended absorption phase very much similar to that of Eskalith with the identical elimination half-life and extent of absorption. Conclusion: The matrix tablets containing 15% CP reduces the incidence of side effects often associated with high serum concentration of Lithium and blood level variations. Direct correlation between the dissolution profiles and the relative bioavailability of the formulations could be observed. Keywords: Lithium carbonate, Matrix tablets, Sustained-release, In vitro

  17. Biofabrication of a PLGA-TCP-based porous bioactive bone substitute with sustained release of icaritin.

    Science.gov (United States)

    Xie, Xin-Hui; Wang, Xin-Luan; Zhang, Ge; He, Yi-Xin; Leng, Yang; Tang, Ting-Ting; Pan, Xiaohua; Qin, Ling

    2015-08-01

    A phytomolecule, icaritin, has been identified and shown to be osteopromotive for the prevention of osteoporosis and osteonecrosis. This study aimed to produce a bioactive poly (l-lactide-co-glycolide)-tricalcium phosphate (PLGA-TCP)-based porous scaffold incorporating the osteopromotive phytomolecule icaritin, using a fine spinning technology. Both the structure and the composition of icaritin-releasing PLGA-TCP-based scaffolds were evaluated by scanning electron microscopy (SEM). The porosity was quantified by both water absorption and micro-computed tomography (micro-CT). The mechanical properties were evaluated using a compression test. In vitro release of icaritin from the PLGA-TCP scaffold was quantified by high-performance liquid chromatography (HPLC). The attachment, proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) on the composite scaffold were evaluated. Both an in vitro cytotoxicity test and an in vivo test via muscular implantation were conducted to confirm the scaffold's biocompatibility. The results showed that the PLGA-TCP-icaritin composite scaffold was porous, with interconnected macro- (about 480 µm) and micropores (2-15 µm). The mechanical properties of the PLGA-TCP-icaritin scaffold were comparable with those of the pure PLGA-TCP scaffold, yet was spinning direction-dependent. Icaritin content was detected in the medium and increased with time. The PLGA-TCP-icaritin scaffold facilitated the attachment, proliferation and osteogenic differentiation of BMSCs. In vitro cytotoxicity test and in vivo intramuscular implantation showed that the composite scaffold had no toxicity with good biocompatibility. In conclusion, an osteopromotive phytomolecule, icaritin, was successfully incorporated into PLGA-TCP to form an innovative porous composite scaffold with sustained release of osteopromotive icaritin, and this scaffold had good biocompatibility and osteopromotion, suggesting its potential for orthopaedic

  18. Modified thermoresponsive Poloxamer 407 and chitosan sol-gels as potential sustained-release vaccine delivery systems

    DEFF Research Database (Denmark)

    Kojarunchitt, Thunjiradasiree; Baldursdottir, Stefania; Dong, Yao-Da

    2015-01-01

    A and monophosphoryl lipid A), were free-flowing liquids at room temperature and formed stable gels at physiological temperatures. Rheological results showed that both systems meet the criteria of being thermoresponsive gels. The P407-25R4 sol-gels did not significantly sustain the release of antigen in vivo while...... the chitosan-MC sol-gels sustained the release of antigen up to at least 14 days after administration. The chitosan-MC sol-gels stimulated both cellular and humoral responses. The inclusion of cubosomes in the sol-gels did not provide a definitive beneficial effect. Further analysis of the formulations...

  19. Hydrophilic thermoplastic polyurethanes for the manufacturing of highly dosed oral sustained release matrices via hot melt extrusion and injection molding.

    Science.gov (United States)

    Verstraete, G; Van Renterghem, J; Van Bockstal, P J; Kasmi, S; De Geest, B G; De Beer, T; Remon, J P; Vervaet, C

    2016-06-15

    Hydrophilic aliphatic thermoplastic polyurethane (Tecophilic™ grades) matrices for high drug loaded oral sustained release dosage forms were formulated via hot melt extrusion/injection molding (HME/IM). Drugs with different aqueous solubility (diprophylline, theophylline and acetaminophen) were processed and their influence on the release kinetics was investigated. Moreover, the effect of Tecophilic™ grade, HME/IM process temperature, extrusion speed, drug load, injection pressure and post-injection pressure on in vitro release kinetics was evaluated for all model drugs. (1)H NMR spectroscopy indicated that all grades have different soft segment/hard segment ratios, allowing different water uptake capacities and thus different release kinetics. Processing temperature of the different Tecophilic™ grades was successfully predicted by using SEC and rheology. Tecophilic™ grades SP60D60, SP93A100 and TG2000 had a lower processing temperature than other grades and were further evaluated for the production of IM tablets. During HME/IM drug loads up to 70% (w/w) were achieved. In addition, Raman mapping and (M)DSC results confirmed the homogenous distribution of mainly crystalline API in all polymer matrices. Besides, hydrophilic TPU based formulations allowed complete and sustained release kinetics without using release modifiers. As release kinetics were mainly affected by drug load and the length of the PEO soft segment, this polymer platform offers a versatile formulation strategy to adjust the release rate of drugs with different aqueous solubility. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Pharmaceutical suspension containing both immediate/sustained-release amoxicillin-loaded gelatin nanoparticles: preparation and in vitro characterization

    Science.gov (United States)

    Harsha, Sree

    2013-01-01

    Pharmaceutical suspension containing oral dosage forms delivering both immediate-release and sustained-release amoxicillin was developed as a new dosage form to eradicate Helicobacter pylori. Amoxicillin-loaded gelatin nanoparticles are able to bind with the mucosal membrane after delivery to the stomach and could escalate the effectiveness of a drug, providing dual release. The objective of this study was to develop amoxicillin nanoparticles using innovative new technology – the Büchi Nano Spray Dryer B-90 – and investigate such features as drug content, particle morphology, yield, in vitro release, flow properties, and stability. The nanoparticles had an average particle size of 571 nm. The drug content and percentage yield was 89.2% ± 0.5% and 93.3% ± 0.6%, respectively. Angle of repose of nanoparticle suspension was 26.3° and bulk density was 0.59 g/cm3. In vitro drug release of formulations was best fitted by first-order and Peppas models with R2 of 0.9841 and 0.9837 respectively; release profile was 15.9%, while; for the original drug, amoxicillin, under the same conditions, 90% was released in the first 30 minutes. The nanoparticles used in this study enabled sustained release of amoxicillin over an extended period of time, up to 12 hours, and were stable for 12 months under accelerated storage conditions of 25°C ± 2°C and 60% ± 5% relative humidity. PMID:24101859

  1. Taste masking of ciprofloxacin by ion-exchange resin and sustain release at gastric-intestinal through interpenetrating polymer network

    Directory of Open Access Journals (Sweden)

    A. Michael Rajesh

    2015-07-01

    Full Text Available The aim of the study was to taste mask ciprofloxacin (CP by using ion-exchange resins (IERs followed by sustain release of CP by forming interpenetrating polymer network (IPN. IERs based on the copolymerization of acrylic acid with different cross linking agents were synthesised. Drug-resin complexes (DRCs with three different ratios of drug to IERs (1:1, 1:2, 1:4 were prepared & evaluated for taste masking by following in vivo and in vitro methods. Human volunteers graded ADC 1:4, acrylic acid-divinyl benzene (ADC-3 resin as tasteless. Characterization studies such as FTIR, SEM, DSC, P-XRD differentiated ADC 1:4, from physical mixture (PM 1:4 and confirmed the formation of complex. In vitro drug release of ADC 1:4 showed complete release of CP within 60 min at simulated gastric fluid (SGF i.e. pH 1.2. IPN beads were prepared with ADC 1:4 by using sodium alginate (AL and sodium alginate-chitosan (AL-CS for sustain release of CP at SGF pH and followed by simulated intestinal fluid (SIF i.e. pH 7.4. FTIR spectra confirmed the formation of IPN beads. The release of CP was sustain at SGF pH (75%. The kinetic model of IPN beads showed the release of CP was non-Fickian diffusion type.

  2. Nanoparticle-based topical ophthalmic formulation for sustained release of stereoisomeric dipeptide prodrugs of ganciclovir.

    Science.gov (United States)

    Yang, Xiaoyan; Shah, Sujay J; Wang, Zhiying; Agrahari, Vibhuti; Pal, Dhananjay; Mitra, Ashim K

    2016-09-01

    Poly(d,l-lactic-co-glycolic acid) (PLGA) nanoparticles (NP) of Val-Val dipeptide monoester prodrugs of ganciclovir (GCV) including L-Val-L-Val-GCV (LLGCV), L-Val-D-Val-GCV (LDGCV) and D-Val-L-Val-GCV (DLGCV) were formulated and dispersed in thermosensitive PLGA-PEG-PLGA polymer gel for the treatment of herpes simplex virus type 1 (HSV-1)-induced viral corneal keratitis. Nanoparticles containing prodrugs of GCV were prepared by a double-emulsion solvent evaporation technique using various PLGA polymers with different drug/polymer ratios. Nanoparticles were characterized with respect to particle size, entrapment efficiency, polydispersity, drug loading, surface morphology, zeta potential and crystallinity. Prodrugs-loaded NP were incorporated into in situ gelling system. These formulations were examined for in vitro release and cytotoxicity. The results of optimized entrapment efficiencies of LLGCV-, LDGCV- and DLGCV-loaded NP are of 38.7 ± 2.0%, 41.8 ± 1.9%, and 45.3 ± 2.2%; drug loadings 3.87 ± 0.20%, 2.79 ± 0.13% and 3.02 ± 0.15%; yield 85.2 ± 3.0%, 86.9 ± 4.6% and 76.9 ± 2.1%; particle sizes 116.6 ± 4.5, 143.0 ± 3.8 and 134.1 ± 5.2 nm; and zeta potential -15.0 ± 4.96, -13.8 ± 5.26 and -13.9 ± 5.14 mV, respectively. Cytotoxicity studies suggested that all the formulations are non-toxic. In vitro release of prodrugs from NP showed a biphasic release pattern with an initial burst phase followed by a sustained phase. Such burst effect was completely eliminated when NP were suspended in thermosensitive gels with near zero-order release kinetics. Prodrugs-loaded PLGA NP dispersed in thermosensitive gels can thus serve as a promising drug delivery system for the treatment of anterior eye diseases.

  3. A sustained release formulation of novel quininib-hyaluronan microneedles inhibits angiogenesis and retinal vascular permeability in vivo.

    Science.gov (United States)

    Galvin, Orla; Srivastava, Akshay; Carroll, Oliver; Kulkarni, Rajiv; Dykes, Steve; Vickers, Steven; Dickinson, Keith; Reynolds, Alison L; Kilty, Claire; Redmond, Gareth; Jones, Rob; Cheetham, Sharon; Pandit, Abhay; Kennedy, Breandán N

    2016-07-10

    Pathologic neovascularisation and ocular permeability are hallmarks of proliferative diabetic retinopathy and age-related macular degeneration. Current pharmacologic interventions targeting VEGF are effective in only 30-60% of patients and require multiple intraocular injections associated with iatrogenic infection. Thus, our goal is to develop novel small molecule drugs that are VEGF-independent are amenable to sustained ocular-release, and which reduce retinal angiogenesis and retinal vascular permeability. Here, the anti-angiogenic drug quininib was formulated into hyaluronan (HA) microneedles whose safety and efficacy was evaluated in vivo. Quininib-HA microneedles were formulated via desolvation from quininib-HA solution and subsequent cross-linking with 4-arm-PEG-amine prior to freeze-drying. Scanning electron microscopy revealed hollow needle-shaped particle ultrastructure, with a zeta potential of -35.5mV determined by electrophoretic light scattering. The incorporation efficiency and pharmacokinetic profile of quininib released in vitro from the microneedles was quantified by HPLC. Quininib incorporation into these microneedles was 90%. In vitro, 20% quininib was released over 4months; or in the presence of increasing concentrations of hyaluronidase, 60% incorporated quininib was released over 4months. Zebrafish hyaloid vasculature assays demonstrated quininib released from these microneedles significantly (pmicroneedles allow for sustained release of quininib; are safe in vivo and quininib released from these microneedles effectively inhibits angiogenesis and RVP in vivo. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Effect of sustained-release isosorbide dinitrate on post-prandial gastric emptying and gastroduodenal motility in healthy humans

    DEFF Research Database (Denmark)

    Madsen, J L; Rasmussen, S L; Linnet, J

    2004-01-01

    and gastroduodenal motility after a meal. Eleven healthy volunteers participated in a double-blind, placebo-controlled, cross-over study. Each subject ingested 40 mg isosorbide dinitrate orally as a sustained-release formulation or oral placebo, in random order. Gastric emptying and gastroduodenal motility were...

  5. Preparation of rifampicin/poly(d,l-lactice) nanoparticles for sustained release by supercritical assisted atomization technique

    CSIR Research Space (South Africa)

    Labuschagne, Philip W

    2014-11-01

    Full Text Available In this work supercritical assisted atomization (SAA) process was used for the co-precipitation of poly(d,l-lactide) (PDLLA) and rifampicin (RIF) as nanoparticles for sustained release applications. The effect of the variation of PDLLA/RIF ratio...

  6. A pillar[5]arene based gel from a low-molecular-weight gelator for sustained dye release in water.

    Science.gov (United States)

    Yao, Yong; Sun, Yan; Yu, Huaxu; Chen, Wenrui; Dai, Hong; Shi, Yujun

    2017-11-24

    A soft gel based on pillar[5]arene was successfully prepared using a carbazone reaction. Furthermore, dyes such as TPP or TPPE can be incorporated into this gel and were observed to be released in a sustained way in water due to solvent exchange.

  7. Managing cancer pain and symptoms of outpatients by rotation to sustained-release hydromorphone: a prospective clinical trial

    NARCIS (Netherlands)

    Wirz, Stefan; Wartenberg, Hans Christian; Elsen, Christian; Wittmann, Maria; Diederichs, Marta; Nadstawek, Joachim

    2006-01-01

    PURPOSE: In this prospective clinical trial we examined the technique of opioid rotation to oral sustained-release hydromorphone for controlling pain and symptoms in outpatients with cancer pain. METHODS: Before and after rotation, 50 patients were assessed by Numerical Analog Scales [Numerical

  8. Sustained release nitrite therapy results in myocardial protection in a porcine model of metabolic syndrome with peripheral vascular disease

    OpenAIRE

    Bradley, Jessica M.; Islam, Kazi N.; Polhemus, David J.; Donnarumma, Erminia; Brewster, Luke P.; Tao, Ya-Xiong; Goodchild, Traci T.; Lefer, David J.

    2015-01-01

    In a clinically relevant porcine model of metabolic syndrome and peripheral vascular disease, treatment with a novel sustained-release nitrite formulation restored cardiac endothelial nitric oxide synthase, enhancing myocardial nitrite levels, reduced oxidative stress, and improved ex vivo coronary vascular function via endothelium-independent vasodilation mechanism in obese Ossabaw swine.

  9. Absorption kinetics and steady-state plasma concentrations of theophylline following therapeutic doses of two sustained-release preparations

    DEFF Research Database (Denmark)

    Nielsen, M K; Eriksen, P B; Fenger, M

    1983-01-01

    Ten healthy volunteers received two sustained-release preparations as a single and multiple dose regimen in an open crossover study. Plasma theophylline concentrations were measured by an enzyme immunoassay. The limited fluctuation of the theophylline levels at steady state, with twice daily...... theophylline concentration....

  10. Encapsulation and sustained release of a model drug, indomethacin, using CO(2)-based microencapsulation.

    Science.gov (United States)

    Liu, H; Finn, N; Yates, M Z

    2005-01-04

    A carbon dioxide (CO(2))-based microencapsulation technique was used to impregnate indomethacin, a model drug, into biodegradable polymer nanoparticles. Compressed CO(2) was emulsified into aqueous suspensions of biodegradable particles. The CO(2) plasticizes the biodegradable polymers, increasing the drug diffusion rate in the particles so that drug loading is enhanced. Four types of biodegradable polymers were investigated, including poly(d,l-lactic acid) (PLA), poly(d,l-lactic acid-co-glycolic acid) (PLGA) with two different molar ratios of LA to GA, and a poly(d,l-lactic acid-b-ethylene glycol) (PLA-PEG) block copolymer. Biodegradable nanoparticles were prepared from polymer solutions through nonsolvent-induced precipitation in the presence of surfactants. Indomethacin was incorporated into biodegradable nanoparticles with no change of the particle size and morphology. The effects of a variety of experimental variables on the drug loadings were investigated. It was found that the drug loading was the highest for PLA homopolymer and decreased in PLGA copolymers as the fraction of glycolic acid increased. Indomethacin was predicted to have higher solubility in PLA than in PLGA based on the calculated solubility parameters. The drug loading in PLA increased markedly as the temperature for impregnation was increased from 35 to 45 degrees C. Drug release from the particles is a diffusion-controlled process, and sustained release can be maintained over 10 h. A simple Fickian diffusion model was used to estimate the diffusion coefficients of indomethacin in the biodegradable polymers. The diffusion coefficients are consistent with previous studies, suggesting that the polymer properties are unchanged by supercritical fluid processing. Supercritical CO(2) is nontoxic, easily separated from the polymers, can extract residual organic solvent, and can sterilize biodegradable polymers. The CO(2)-based microencapsulation technique is promising for the production of drug

  11. Design and in vitro/in vivo evaluation of sustained-release floating tablets of itopride hydrochloride

    Directory of Open Access Journals (Sweden)

    Ahmed SM

    2016-12-01

    Full Text Available Sayed M Ahmed,1 Adel Ahmed Ali,2 Ahmed MA Ali,2,3 Omiya A Hassan2,4 1Department of Industrial Pharmacy, Faculty of Pharmacy, Assiut University, Assiut, 2Department of Pharmaceutics, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt; 3Department of Pharmaceutics, Faculty of Pharmacy, Taif University, Taif, Kingdom of Saudi Arabia; 4Department of Pharmaceutics, Faculty of Pharmacy, Deraya University, El-Minia Gadida, Egypt Purpose: The aim of the present study was to improve the bioavailability of itopride (ITO and sustain its action by formulating as a floating dosage form. Materials and methods: Sustained-release floating tablets of ITO hydrochloride (HCl were prepared by direct compression using different hydrocolloid polymers such as hydroxypropyl methylcellulose and ethylcellulose and/or methacrylic acid polymers Eudragit RSPM and Carbopol 934P. The floating property was achieved using an effervescent mixture of sodium bicarbonate and anhydrous citric acid (1:1 mol/mol. Hardness, friability, content uniformity, and dissolution rate of the prepared floating tablets were evaluated. The formulation F10 composed of 28.5% Eudragit RSPM, 3% NaHCO3, and 7% citric acid provided sustained drug release. Results: In vitro results showed sustained release of F10 where the drug release percentage was 96.51%±1.75% after 24 hours (P=0.031.The pharmacokinetic results indicated that the area under the curve (AUC0–∞ of the prepared sustained-release floating tablets at infinity achieved 93.69 µg·h/mL compared to 49.89 µg·h/mL for the reference formulation (Ganaton® and the relative bioavailability of the sustained-release formulation F10 increased to 187.80% (P=0.022. Conclusion: The prepared floating tablets of ITO HCl (F10 could be a promising drug delivery system with sustained-release action and enhanced drug bioavailability. Keywords: itopride HCl, oral drug delivery, stability study, bioavailability

  12. Sustained release of hydrophilic drug from polyphosphazenes/poly(methyl methacrylate) based microspheres and their degradation study.

    Science.gov (United States)

    Akram, Muhammad; Yu, Haojie; Wang, Li; Khalid, Hamad; Abbasi, Nasir M; Zain-ul-Abdin; Chen, Yongsheng; Ren, Fujie; Saleem, Muhammad

    2016-01-01

    Drug delivery system is referred as an approach to deliver the therapeutic agents to the target site safely in order to achieve the maximum therapeutic effects. In this perspective, synthesis of three new polyphosphazenes and their blend fabrication system with poly(methyl methacrylate) is described and characterized with (1)H NMR, (31)P NMR, GPC and DSC. Furthermore, these novel blends were used to fabricate microspheres and evaluated for sustain release of hydrophilic drug (aspirin as model drug). Microspheres of the two blends showed excellent encapsulation efficacy (about 93%), controlled burst release (2.3% to 7.93%) and exhibited sustain in vitro drug release (13.44% to 32.77%) up to 218 h. At physiological conditions, the surface degradation of microspheres and diffusion process controlled the drug release sustainability. Furthermore, it was found that the degree of porosity was increased with degradation and the resulting porous network was responsible for water retention inside the microspheres. The percentage water retention was found to be interrelated with degradation time and percentage drug release. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. Evaluation of formulation and effects of process parameters on drug release and mechanical properties of tramadol hydrocloride sustained release matrix tablets

    Directory of Open Access Journals (Sweden)

    Nikolić Nenad D.

    2015-01-01

    Full Text Available This study investigates using of high molecular weight polyethylene oxide (PEO WSR Coagulant for the preparation of sustained release matrix tablets containing high dose, highly water soluble drug, tramadol HCl. Proportion of PEO polymer, type of insoluble filler, proportion of tramadol HCl, amount of drug in tablet, tablet diameter and compression pressure were recognized as critical formulation and process parameters and their influence on drug release and tablet mechanical properties was evaluated. Percentages of tramadol HCl released after 30 and 240 minutes were selected for evaluation of drug release, while tensile strength was used as indicator of tablet mechanical properties. Only proportion of tramadol HCl exhibits statistically significant effect on percentages of tramadol HCl released after 30 and 240 minutes, with higher, wherein increasing of the tramadol HCl proportion increased its release rate among the evaluated variables in selected ranges. All of the investigated factors exhibit statistically significant effect on tablets tensile strength, with the largest influence of filler type. Tablets prepared with highly compressible filler (microcrystalline celullose exhibit higher tensile strength and therefore better mechanical properties to those prepared with partially pregelatinised starch (Strach 1500. [Projekat Ministarstva nauke Republike Srbije, br. TR 34007

  14. Preparation and evaluation of sustained-release matrix tablets based on metoprolol and an acrylic carrier using injection moulding.

    Science.gov (United States)

    Quinten, T; Andrews, G P; De Beer, T; Saerens, L; Bouquet, W; Jones, D S; Hornsby, P; Remon, J P; Vervaet, C

    2012-12-01

    Sustained-release matrix tablets based on Eudragit RL and RS were manufactured by injection moulding. The influence of process temperature; matrix composition; drug load, plasticizer level; and salt form of metoprolol: tartrate (MPT), fumarate (MPF) and succinate (MPS) on ease of processing and drug release were evaluated. Formulations composed of 70/30% Eudragit RL/MPT showed the fastest drug release, substituting part of Eudragit RL by RS resulted in slower drug release, all following first-order release kinetics. Drug load only affected drug release of matrices composed of Eudragit RS: a higher MPT concentration yielded faster release rates. Adding triethyl citrate enhanced the processability, but was detrimental to long-term stability. The process temperature and plasticizer level had no effect on drug release, whereas metoprolol salt form significantly influenced release properties. The moulded tablets had a low porosity and a smooth surface morphology. A plasticizing effect of MPT, MPS and MPF on Eudragit RS and Eudragit RL was observed via DSC and DMA. Solubility parameter assessment, thermal analysis and X-ray diffraction demonstrated the formation of a solid solution immediately after production, in which H-bonds were formed between metoprolol and Eudragit as evidenced by near-infrared spectroscopy. However, high drug loadings of MPS and MPF showed a tendency to recrystallise during storage. The in vivo performance of injection-moulded tablets was strongly dependent upon drug loading.

  15. Formation of mannitol core microparticles for sustained release with lipid coating in a mini fluid bed system.

    Science.gov (United States)

    Wang, Bifeng; Friess, Wolfgang

    2017-11-01

    The goal of this study was to prepare sustained release microparticles for methyl blue and aspartame as sparingly and freely water-soluble model drugs by lipid film coating in a Mini-Glatt fluid bed, and to assess the effect of coating load of two of lipids, hard fat and glyceryl stearate, on the release rates. 30g drug-loaded mannitol carrier microparticles with average diameter of 500 or 300μm were coated with 5g, 10g, 20g and 30g lipids, respectively. The model drugs were completely released in vitro through pores which mainly resulted from dissolution of the polyol core beads. The release of methyl blue from microparticles based on 500μm carrier beads extended up to 25days, while aspartame release from microparticles formed from 300μm carrier beads was extended to 7days. Although glyceryl stearate exhibits higher wettability, burst and release rates were similar for the two lipid materials. Polymorphic transformation of the hart fat was observed upon release. The lipid-coated microparticles produced with 500μm carrier beads showed slightly lower burst release compared to the microparticles produced with 300μm carrier beads as they carried relatively thicker lipid layer based on an equivalent lipid to mannitol ratio. Aspartame microparticles showed a much faster release than methyl blue due to the higher water-solubility of aspartame. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Electrostatic self-assembly of multilayer copolymeric membranes on the surface of porous tantalum implants for sustained release of doxorubicin.

    Science.gov (United States)

    Guo, Xinming; Chen, Muwan; Feng, Wenzhou; Liang, Jiabi; Zhao, Huibin; Tian, Lin; Chao, Hui; Zou, Xuenong

    2011-01-01

    Many studies in recent years have focused on surface engineering of implant materials in order to improve their biocompatibility and other performance. Porous tantalum implants have increasingly been used in implant surgeries, due to their biocompatibility, physical stability, and good mechanical strength. In this study we functionalized the porous tantalum implant for sustained drug delivery capability via electrostatic self-assembly of polyelectrolytes of hyaluronic acid, methylated collagen, and terpolymer on the surface of a porous tantalum implant. The anticancer drug doxorubicin was encapsulated into the multilayer copolymer membranes on the porous tantalum implants. Results showed the sustained released of doxorubicin from the functionalized porous tantalum implants for up to 1 month. The drug release solutions in 1 month all had inhibitory effects on the proliferation of chondrosarcoma cell line SW1353. These results suggest that this functionalized implant could be used in reconstructive surgery for the treatment of bone tumor as a local, sustained drug delivery system.

  17. Formulation and evaluation of rifampicin sustained release tablets using juice of Citrus limetta as bio-retardant

    Directory of Open Access Journals (Sweden)

    K Pawan Gaur

    2012-01-01

    Full Text Available The advantages of biopolymers over synthetic polymers are low cost, natural origin, free from side effects, biocompatible, bio-acceptable, environmental friendly processing, local availability, better patient tolerance as well as public acceptance. Sustained release tablets containing rifampicin was prepared by adding 100 mg polymer and 50 mg Drug and Granules. Same procedure was followed with 3% and 5% of polymer for preparation of sustained release tablets. Additional Tablets of 100 mg, 200 mg and 400 mg were prepared using 5% of the polymer. The results indicated that the selected biopolymer had a good release retardant property thus it can be concluded that the selected biopolymer can be utilized as low cost natural biocompatible and biodegradable agent.

  18. Genome-wide association study of d-amphetamine response in healthy volunteers identifies putative associations, including cadherin 13 (CDH13.

    Directory of Open Access Journals (Sweden)

    Amy B Hart

    Full Text Available Both the subjective response to d-amphetamine and the risk for amphetamine addiction are known to be heritable traits. Because subjective responses to drugs may predict drug addiction, identifying alleles that influence acute response may also provide insight into the genetic risk factors for drug abuse. We performed a Genome Wide Association Study (GWAS for the subjective responses to amphetamine in 381 non-drug abusing healthy volunteers. Responses to amphetamine were measured using a double-blind, placebo-controlled, within-subjects design. We used sparse factor analysis to reduce the dimensionality of the data to ten factors. We identified several putative associations; the strongest was between a positive subjective drug-response factor and a SNP (rs3784943 in the 8(th intron of cadherin 13 (CDH13; P = 4.58×10(-8, a gene previously associated with a number of psychiatric traits including methamphetamine dependence. Additionally, we observed a putative association between a factor representing the degree of positive affect at baseline and a SNP (rs472402 in the 1(st intron of steroid-5-alpha-reductase-α-polypeptide-1 (SRD5A1; P = 2.53×10(-7, a gene whose protein product catalyzes the rate-limiting step in synthesis of the neurosteroid allopregnanolone. This SNP belongs to an LD-block that has been previously associated with the expression of SRD5A1 and differences in SRD5A1 enzymatic activity. The purpose of this study was to begin to explore the genetic basis of subjective responses to stimulant drugs using a GWAS approach in a modestly sized sample. Our approach provides a case study for analysis of high-dimensional intermediate pharmacogenomic phenotypes, which may be more tractable than clinical diagnoses.

  19. Methamphetamine-, d-Amphetamine-, and p-Chloroamphetamine-Induced Neurotoxicity Differentially Effect Impulsive Responding on the Stop-Signal Task in Rats.

    Science.gov (United States)

    Furlong, Teri M; Leavitt, Lee S; Keefe, Kristen A; Son, Jong-Hyun

    2016-05-01

    Abused amphetamines, such as d-amphetamine (AMPH) and methamphetamine (METH), are highly addictive and destructive to health and productive lifestyles. The abuse of these drugs is associated with impulsive behavior, which is likely to contribute to addiction. The amphetamines also differentially damage dopamine (DA) and serotonin (5-HT) systems, which regulate impulsive behavior; therefore, exposure to these drugs may differentially alter impulsive behavior to effect the progression of addiction. We examined the impact of neurotoxicity induced by three amphetamines on impulsive action using a stop-signal task in rats. Animals were rewarded with a food pellet after lever pressing (i.e., a go trial), unless an auditory cue was presented and withholding lever press gained reward (i.e., a stop trial). Animals were trained on the task and then exposed to a neurotoxic regimen of either AMPH, p-chloroamphetamine (PCA), or METH. These regimens preferentially reduced DA transporter levels in striatum, 5-HT transporter levels in prefrontal cortex, or both, respectively. Assessment of performance on the stop-signal task beginning 1 week after the treatment revealed that AMPH produced a deficit in go-trial performance, whereas PCA did not alter performance on either trial type. In contrast, METH produced a deficit in stop-trial performance (i.e., impulsive action) but not go-trial performance. These findings suggest that the different neurotoxic consequences of substituted amphetamines are associated with different effects on inhibitory control over behavior. Thus, the course of addiction and maladaptive behavior resulting from exposure to these substances is likely to differ.

  20. Self-assembly of amphiphilic Janus dendrimers into mechanically robust supramolecular hydrogels for sustained drug release.

    Science.gov (United States)

    Nummelin, Sami; Liljeström, Ville; Saarikoski, Eve; Ropponen, Jarmo; Nykänen, Antti; Linko, Veikko; Seppälä, Jukka; Hirvonen, Jouni; Ikkala, Olli; Bimbo, Luis M; Kostiainen, Mauri A

    2015-10-05

    Compounds that can gelate aqueous solutions offer an intriguing toolbox to create functional hydrogel materials for biomedical applications. Amphiphilic Janus dendrimers with low molecular weights can readily form self-assembled fibers at very low mass proportion (0.2 wt %) to create supramolecular hydrogels (G'≫G'') with outstanding mechanical properties and storage modulus of G'>1000 Pa. The G' value and gel melting temperature can be tuned by modulating the position or number of hydrophobic alkyl chains in the dendrimer structure; thus enabling exquisite control over the mesoscale material properties in these molecular assemblies. The gels are formed within seconds by simple injection of ethanol-solvated dendrimers into an aqueous solution. Cryogenic TEM, small-angle X-ray scattering, and SEM were used to confirm the fibrous structure morphology of the gels. Furthermore, the gels can be efficiently loaded with different bioactive cargo, such as active enzymes, peptides, or small-molecule drugs, to be used for sustained release in drug delivery. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Role of sustained antigen release from nanoparticle vaccines in shaping the T cell memory phenotype.

    Science.gov (United States)

    Demento, Stacey L; Cui, Weiguo; Criscione, Jason M; Stern, Eric; Tulipan, Jacob; Kaech, Susan M; Fahmy, Tarek M

    2012-06-01

    Particulate vaccines are emerging promising technologies for the creation of tunable prophylactics against a wide variety of conditions. Vesicular and solid biodegradable polymer platforms, exemplified by liposomes and polyesters, respectively, are two of the most ubiquitous platforms in vaccine delivery studies. Here we directly compared the efficacy of each in a long-term immunization study and in protection against a model bacterial antigen. Immunization with poly(lactide-co-glycolide) (PLGA) nanoparticles elicited prolonged antibody titers compared to liposomes and alum. The magnitude of the cellular immune response was also highest in mice vaccinated with PLGA, which also showed a higher frequency of effector-like memory T cell phenotype, leading to an effective clearance of intracellular bacteria. The difference in performance of these two common particulate platforms is shown not to be due to material differences but appears to be connected to the kinetics of antigen delivery. Thus, this study highlights the importance of sustained antigen release mediated by particulate platforms and its role in the long-term appearance of effector memory cellular response. Copyright © 2012 Elsevier Ltd. All rights reserved.

  2. Treatment of Gastrin-Secreting Tumor With Sustained-Release Octreotide Acetate in a Dog.

    Science.gov (United States)

    Kim, Sangho; Hosoya, Kenji; Takagi, Satoshi; Okumura, Masahiro

    2015-01-01

    An 8 yr old, intact male Shiba Inu was presented with loose stool, polydipsia, hematuria, vomiting, and anorexia. On abdominal ultrasonography, numerous nodules were detected in the hepatic parenchyma distributed diffusely throughout all lobes. Excisional biopsy of one of the nodules was performed via exploratory laparotomy. A histopathological diagnosis of the lesion was carcinoid, and the tumor cells stained positive to chromogranin A and gastrin. The serum gastrin level of the dog was 45,613 pg/mL (reference range: 160-284). In addition to medical treatment with omeprazole(c) and famotidine(e), suppression of gastrin secretion was attempted with octreotide acetate. A test dose of octreotide acetate significantly decreased the serum gastrin level to approximately one third of the baseline in 2 hr and the effect lasted approximately for 6 hr. On day 21, treatment with sustained-release formulation of octreotide acetate(a) (5 mg intramuscular, q 4 wk) was initiated. The serum gastrin concentration gradually decreased over 32 days and then progressively increased in parallel with the progression of the hepatic nodules. The dog gradually developed recurrence of initial clinical signs, and was lost to follow-up on day 510.

  3. Bupropion sustained release in adolescents with comorbid attention-deficit/hyperactivity disorder and depression.

    Science.gov (United States)

    Daviss, W B; Bentivoglio, P; Racusin, R; Brown, K M; Bostic, J Q; Wiley, L

    2001-03-01

    To determine whether bupropion sustained release (SR) is effective and well-tolerated in adolescents with comorbid attention-deficit/hyperactivity disorder (ADHD) and depression. Subjects were 24 adolescents (aged 11-16 years old) with ADHD and either major depressive disorder or dysthymic disorder. After a 2-week, single-blind placebo lead-in, subjects were treated for 8+ weeks with bupropion SR at doses flexibly titrated up to 3 mg/kg b.i.d. (mean final doses: 2.2 mg/kg q A.M. and 1.7 mg/kg q P.M.). Outcomes were global improvement in ADHD and depression (clinician-rated), along with changes in depressive symptomatology (parent- and child-rated), ADHD symptomatology (parent- and teacher-rated), and functional impairment (parent-rated). Clinicians rated 14 subjects (58%) responders in both depression and ADHD, 7 (29%) responders in depression only, and 1 (4%) a responder in ADHD only. Compared with post-placebo ratings, final parents' (p depressive symptomatology improved significantly, as did parents' (p depressive disorders. However, randomized, placebo-controlled studies are needed.

  4. Effectiveness and tolerability of tapentadol sustained release in the Australian setting.

    Science.gov (United States)

    Russo, Marc A; Santarelli, Danielle M

    2016-01-01

    To assess the effectiveness and tolerability of tapentadol sustained release (SR) following its introduction to the Australian private market. A retrospective audit of routine clinical practice with data collection beginning 2 months after the first tapentadol SR prescription. A multidisciplinary Australian pain clinic. Fifty patients who were prescribed tapentadol SR as part of routine clinical management at the pain clinic. Trial of tapentadol SR with subsequent dose titration if the patient was satisfied with or tolerant of the medication. Patient-reported pain outcome, side effects, medication adherence, and concomitant analgesic medications. Sixty-eight percent of patients reported major reductions in pain. Seventy-two percent of patients tolerated and adhered to treatment and 76 percent reported no side effects. Pain outcome was independent of pain type and prior opioid exposure; however, patients taking tapentadol in combination were more likely to report a positive outcome (Pearson χ(2) = 9.867, n = 46, p = 0.0072). Tapentadol was effective and generally well tolerated in the majority of patients for neuropathic, nociceptive and mixed pain types and this was regardless of prior opioid use.

  5. Laboratory and Field Evaluation of Biodegradable Polyesters for Sustained Release of Isometamidium and Ethidium

    Directory of Open Access Journals (Sweden)

    Geerts S

    1999-01-01

    Full Text Available An overview is presented of the results obtained with biodegradable sustained release devices (SRDs containing a mixture of polymers and either isometamidium (ISMM or ethidium. Under controlled laboratory conditions (monthly challenge with tsetse flies infected with Trypanosoma congolense the protection period in SRD treated cattle could be extended by a factor 2.8 (for ethidium up to 4.2 (for ISMM as compared to animals treated intramuscularly with the same drugs. Using a competitive drug ELISA ISMM concentrations were detected up to 330 days after the implantation of the SRDs, whereas after i.m. injection the drug was no longer present three to four months post treatment. Two field trials carried out in Mali under heavy tsetse challenge showed that the cumulative infection rate was significantly lower in the ISMM-SRD implanted cattle than in those which received ISMM intramuscularly. Using ethidium SRD, however, contradictory results were obtained in field trials in Zambia and in Mali. The potential advantages and inconvenients of the use of SRDs are discussed and suggestions are made in order to further improve the currently available devices.

  6. Advances in Hybrid Polymer-Based Materials for Sustained Drug Release

    Directory of Open Access Journals (Sweden)

    Lígia N. M. Ribeiro

    2017-01-01

    Full Text Available The use of biomaterials composed of organic pristine components has been successfully described in several purposes, such as tissue engineering and drug delivery. Drug delivery systems (DDS have shown several advantages over traditional drug therapy, such as greater therapeutic efficacy, prolonged delivery profile, and reduced drug toxicity, as evidenced by in vitro and in vivo studies as well as clinical trials. Despite that, there is no perfect delivery carrier, and issues such as undesirable viscosity and physicochemical stability or inability to efficiently encapsulate hydrophilic/hydrophobic molecules still persist, limiting DDS applications. To overcome that, biohybrid systems, originating from the synergistic assembly of polymers and other organic materials such as proteins and lipids, have recently been described, yielding molecularly planned biohybrid systems that are able to optimize structures to easily interact with the targets. This work revised the biohybrid DDS clarifying their advantages, limitations, and future perspectives in an attempt to contribute to further research of innovative and safe biohybrid polymer-based system as biomaterials for the sustained release of active molecules.

  7. Isolation and physicochemical characterization of sustained releasing starches from Dioscorea of Jharkhand.

    Science.gov (United States)

    Deepika, V; Jayaram Kumar, K; Anima, P

    2013-04-01

    Starches were isolated from varieties of Dioscorea (Da1, Da2) grown in Jharkhand state of India and it was characterized in terms of moisture, ash, amylose content, bulk density, tapped density, true density, porosity, Carr's index, Hausner's ratio, swelling power, solubility, water holding capacity, paste clarity. Morphological, thermal and IR spectroscopic studies were also done to characterize the isolated starch. The shape and size of starch granules were round/oval to ellipsoid and 5-10μm. There were considerable differences in powder characteristics, amylose content, ash values, and water holding capacity, swelling and solubility power. Starch from variety Da2 showed high enthalpy of gelatinization temperature as compared to variety Da1. Peaks in FTIR spectra of both starches revealed its carbohydrate nature. In vitro studies revealed that both the starches from Da1 and Da2 can be used in developing sustained release formulations. The result showed that starches from both Dioscorea can be used in pharmaceutical industries as excipients with minimal modifications. Copyright © 2013. Published by Elsevier B.V.

  8. Development and characterization of gastroretentive sustained-release formulation by combination of swelling and mucoadhesive approach: a mechanistic study.

    Science.gov (United States)

    Sankar, R; Jain, Subheet Kumar

    2013-01-01

    Acyclovir has pharmacokinetic limitations, including poor oral bioavailability of 15%-30%, high variability, and short elimination half-life of 2.3 hours. These limitations necessitate frequent administration of acyclovir, up to five times daily, leading to poor patient compliance, which in turn leads to a reduction in therapeutic efficacy and development of resistance. A gastroretentive sustained-release (GR) formulation of acyclovir, based on a combination of swelling and mucoadhesive mechanisms, has been developed. Composition has been optimized after evaluation of different polymers, carbomer, polyethylene oxide, and sodium alginate alone and/or in combination. GR formulations were characterized for in-process quality-control tests, drug release and release rate kinetics, similarity factor analysis, swelling index, and matrix erosion. A formulation containing a combination of carbomer and polyethylene oxide had the highest similarity of drug release compared with a target drug-release profile obtained by pharmacokinetic simulations. The measurement of mucoadhesive strength, carried out with a texture analyzer, showed that the mucoadhesive strength of the GR formulation was significantly higher than that of the immediate-release (IR) tablet. The optimized GR formulation was found to be retained in the upper part of the gastrointestinal tract for 480 minutes; the IR tablet was retained for only 90 minutes as measured using a gastrointestinal retention study in albino rabbits. The GR formulation was also found to maintain more sustained plasma concentrations than the IR tablet. Mean residence time of the GR formulation was 7 hours versus 3.3 hours for the IR formulation. The relative bioavailability of the GR formulation was 261% of the IR formulation. The GR formulation of acyclovir, based on swelling and mucoadhesive mechanisms, has prolonged retention in the upper gastrointestinal tract, sustained in vitro drug release, prolonged in vivo absorption, and better

  9. Evaluation of superabsorbent linseed-polysaccharides as a novel stimuli-responsive oral sustained release drug delivery system.

    Science.gov (United States)

    Haseeb, Muhammad Tahir; Hussain, Muhammad Ajaz; Bashir, Sajid; Ashraf, Muhammad Umer; Ahmad, Naveed

    2017-03-01

    Advancement in technology has transformed the conventional dosage forms to intelligent drug delivery systems. Such systems are helpful for targeted and efficient drug delivery with minimum side effects. Drug release from these systems is governed and controlled by external stimuli (pH, enzymes, ions, glucose, etc.). Polymeric biomaterial having stimuli-responsive properties has opened a new area in drug delivery approach. Potential of a polysaccharide (rhamnogalacturonan)-based hydrogel from Linseeds (Linum usitatissimum L.) was investigated as an intelligent drug delivery material. Different concentrations of Linseed hydrogel (LSH) were used to prepare caffeine and diacerein tablets and further investigated for pH and salt solution-responsive swelling, pH-dependent drug release, and release kinetics. Morphology of tablets was observed using SEM. LSH tablets exhibited dynamic swelling-deswelling behavior with tendency to swell at pH 7.4 and in deionized water while deswell at pH 1.2, in normal saline and ethanol. Consequently, pH controlled release of the drugs was observed from tablets with lower release (drug release was greatly influenced by the amount of LSH in the tablets. Drug release from LSH tablets was governed by the non-Fickian diffusion. These finding indicates that LSH holds potential to be developed as sustained release material for tablet.

  10. Characterization and evaluation of self-nanoemulsifying sustained-release pellet formulation of ziprasidone with enhanced bioavailability and no food effect.

    Science.gov (United States)

    Miao, Yanfei; Chen, Guoguang; Ren, Lili; Pingkai, Ouyang

    2016-09-01

    The purpose of this work was to develop self-nanomulsifying drug delivery systems (SNEDDS) in sustained-release pellets of ziprasidone to enhance the oral bioavailability and overcome the food effect of ziprasidone. Preformulation studies including screening of excipients for solubility and pseudo-ternary phase diagrams suggested the suitability of Capmul MCM as oil phase, Labrasol as surfactant, and PEG 400 as co-surfactant for preparation of self-nanoemulsifying formulations. Preliminary composition of the SNEDDS formulations were selected from the pseudo-ternary phase diagrams. The prepared ziprasidone-SNEDDS formulations were characterized for self-emulsification time, effect of pH and robustness to dilution, droplet size analysis and zeta potential. The optimized ziprasidone-SNEDDS were used to prepare ziprasidone-SNEDDS sustained-release pellets via extrusion-spheronization method. The pellets were characterized for SEM, particle size, droplet size distribution and zeta potential. In vitro drug release studies indicated the ziprsidone-SNEDDS sustained-release pellets showed sustained release profiles with 90% released within 10 h. The ziprsidone-SNEDDS sustained-release pellets were administered to fasted and fed beagle dogs and their pharmacokinetics were compared to commercial formulation of Zeldox as a control. Pharmacokinetic studies in beagle dogs showed ziprasidone with prolonged actions and enhanced bioavailability with no food effect was achieved simultaneously in ziprsidone-SNEDDS sustained-release pellets compared with Zeldox in fed state. The results indicated a sustained release with prolonged actions of schizophrenia and bipolar disorder treatment.

  11. Adderall produces increased striatal dopamine release and a prolonged time course compared to amphetamine isomers.

    Science.gov (United States)

    Joyce, B Matthew; Glaser, Paul E A; Gerhardt, Greg A

    2007-04-01

    Adderall is currently used for the treatment of Attention-Deficit Hyperactivity Disorder (ADHD) and is composed of a novel mixture of approximately 24% L-amphetamine and 76% D-amphetamine salts. There are, however, no investigations of the pharmacological effects of this combination in vivo. The technique of high-speed chronoamperometry using Nafion-coated single carbon-fiber microelectrodes was used to study amphetamine-evoked dopamine (DA) release produced by Adderall, D-amphetamine, or D,L-amphetamine in the striatum of anesthetized male Fischer 344 (F344) rats. The amphetamine solutions were locally applied from micropipettes by pressure ejection. Local applications of Adderall resulted in significantly greater DA release signal amplitudes with prolonged time course of dopamine release and re-uptake as compared to D-amphetamine and D,L-amphetamine. These data support the hypothesis that the combination of amphetamine enantiomers and salts in Adderall has effects on DA release, which result in increased and prolonged DA release, compared to D- and D,L-amphetamine.

  12. Comparative bioequivalence studies of tramadol hydrochloride sustained-release 200 mg tablets

    Directory of Open Access Journals (Sweden)

    Suhas S Khandave

    2010-11-01

    Full Text Available Suhas S Khandave1, Satish V Sawant1, Santosh S Joshi1, Yatish K Bansal2, Sonal S Kadam21Accutest Research Laboratories (I Private Limited, Koparkhirne, Navi Mumbai, Maharashtra, India; 2Ipca Laboratories Limited, Kandivli Mumbai, Maharashtra, IndiaBackground: Tramadol hydrochloride is available as 50 mg immediate-release (IR and 100 mg, 200 mg, and 300 mg sustained-release (SR tablets. The recommended dose of tramadol is 50–100 mg IR tablets every 4–6 hours. The tramadol SR 200 mg tablet is a better therapeutic option, with a reduced frequency of dosing, and improved patient compliance and quality of life. The present study evaluated the bioequivalence of a generic tramadol SR 200 mg tablet.Methods: A comparative in vitro dissolution study was performed on the test and reference products, followed by two separate single-dose bioequivalence studies under fasting and fed conditions and one multiple-dose bioequivalence study under fasting conditions. These bioequivalence studies were conducted in healthy human subjects using an open-label, randomized, two-treatment, two-period, two-sequence, crossover design. The oral administration of the test and reference products was done on day 1 for both the single-dose studies and on days 1–5 for the multiple-dose study in each study period as per the randomization code. Serial blood samples were collected at predefined time points in all the studies. Analysis of plasma concentrations of tramadol and O-desmethyltramadol (the M1 metabolite was done by a validated liquid chromatography-mass spectrometry analytical method. The standard acceptance criterion of bioequivalence was applied on log-transformed pharmacokinetic parameters for tramadol and its M1 metabolite.Results: The ratios for geometric least-square means and 90% confidence intervals were within the acceptance range of 80%–125% for log-transformed primary pharmacokinetic parameters for tramadol and its M1 metabolite in all the three studies

  13. Formulation and evaluation of sustained release matrix tablets of pioglitazone hydrochloride using processed Aloe vera mucilage as release modifier

    Directory of Open Access Journals (Sweden)

    Manoj Choudhary

    2015-01-01

    Full Text Available Background: Natural gums and mucilage which hydrates and swells on contact with aqueous media are used as additives in the formulation of hydrophilic drug delivery system. Aim: The purpose of this study was to develop a new monolithic matrix system for complete delivery of Pioglitazone hydrochloride (HCl, in a zero-order manner over an extended time period using processed Aloe vera gel mucilage (PAG as a release modifier. Materials and Methods: The matrices were prepared by dry blending of selected ratios of polymer and ingredients using direct compression technique. Physicochemical properties of dried powdered mucilage of A. vera were studied. Various formulations of pioglitazone HCl and A. vera mucilage were prepared using different drug: Polymer ratios viz., 1:1, 1:2, 1:3, 1:4, 1:5 for PAG by direct compression technique. Results: The formulated matrix tablets were found to have better uniformity of weight and drug content with low statistical deviation. The swelling behavior and in vitro release rate characteristics were also studied. Conclusion: The study proved that the dried A. vera mucilage can be used as a matrix forming material for controlled release of Pioglitazone HCl matrix tablets.

  14. Psyllium: a promising polymer for sustained release formulations in combination with HPMC polymers.

    Science.gov (United States)

    Kaialy, Waseem; Emami, Parastou; Asare-Addo, Kofi; Shojaee, Saeed; Nokhodchi, Ali

    2014-05-01

    Psyllium has a mucilaginous property that makes it a good candidate to be utilized as an excipient in the preparation of controlled release systems. Various formulations were prepared using theophylline as a model drug and investigated with a view to achieve an ideal slow drug release profile. The addition of hydroxypropyl methylcellulose (HPMC) to psyllium significantly reduced the burst release; however, the percentage of drug release within a 12 h period was too slow and thereby inadequate. This was overcome by the addition of lactose as a hydrophilic filler that enabled a slow release with roughly 80% drug release in 12 h. The inclusion of HPMC within psyllium formulations changed the drug release kinetics from Fickian diffusion to anomalous transport. Granulated formulations demonstrated slower drug release than ungranulated or physical mixture and caused a change in the dissolution kinetics from Fickian diffusion to anomalous transport. Milled granules showed more efficient controlled drug release with no burst release. Milling of the granules also changed the drug release kinetics to anomalous transport. Although psyllium was proved to be a promising polymer to control the drug release, a combination of psyllium-HPMC and formulation processes should be considered in an attempt to achieve a zero-order release.

  15. Pharmacokinetic Profiles of Meloxicam and Sustained-release Buprenorphine in Prairie Dogs (Cynomys ludovicianus).

    Science.gov (United States)

    Cary, Cynthia D; Lukovsky-Akhsanov, Nicole L; Gallardo-Romero, Nadia F; Tansey, Cassandram M; Ostergaard, Sharon D; Taylor, Willie D; Morgan, Clint N; Powell, Nathaniel; Lathrop, George W; Hutson, Christina L

    2017-03-01

    In this study, we evaluated the pharmacokinetic profiles of meloxicam and sustained-release (SR) buprenorphine in prairie dogs. The 4 treatment groups were: low-dose meloxicam (0.2 mg/kg SC), high-dose meloxicam (4 mg/kg SC), low-dose buprenorphine SR (0.9 mg/kg SC), and high-dose buprenorphine SR (1.2 mg/kg SC). The highest plasma concentrations occurred within 4 h of administration for both meloxicam treatment groups. The therapeutic range of meloxicam in prairie dogs is currently unknown. However, as compared with the therapeutic range documented in other species (0.39 - 0.91 μg/mL), the mean plasma concentration of meloxicam fell below the minimal therapeutic range prior to 24 h in the low-dose group but remained above therapeutic levels for more than 72 h in the high-dose group. These findings suggest that the current meloxicam dosing guidelines may be subtherapeutic for prairie dogs. The highest mean plasma concentration for buprenorphine SR occurred at the 24-h time point (0.0098 μg/mL) in the low-dose group and at the 8-h time point (0.015 μg/mL) for the high-dose group. Both dosages of buprenorphine SR maintained likely plasma therapeutic levels (0.001 μg/mL, based on previous rodent studies) beyond 72 h. Given the small scale of the study and sample size, statistical analysis was not performed. The only adverse reactions in this study were mild erythematous reactions at injection sites for buprenorphine SR.

  16. Pharmacokinetics and pharmacodynamics of buprenorphine and sustained-release buprenorphine after administration to adult alpacas.

    Science.gov (United States)

    Dooley, S Bryce; Aarnes, Turi K; Lakritz, Jeffrey; Lerche, Phillip; Bednarski, Richard M; Hubbell, John A E

    2017-03-01

    OBJECTIVE To determine pharmacokinetics and pharmacodynamics of buprenorphine after IV and SC administration and of sustained-release (SR) buprenorphine after SC administration to adult alpacas. ANIMALS 6 alpacas. PROCEDURES Buprenorphine (0.02 mg/kg, IV and SC) and SR buprenorphine (0.12 mg/kg, SC) were administered to each alpaca, with a 14-day washout period between administrations. Twenty-one venous blood samples were collected over 96 hours and used to determine plasma concentrations of buprenorphine. Pharmacokinetic parameters were calculated by use of noncompartmental analysis. Pharmacodynamic parameters were assessed via sedation, heart and respiratory rates, and thermal and mechanical antinociception indices. RESULTS Mean ± SD maximum concentration after IV and SC administration of buprenorphine were 11.60 ± 4.50 ng/mL and 1.95 ± 0.80 ng/mL, respectively. Mean clearance was 3.00 ± 0.33 L/h/kg, and steady-state volume of distribution after IV administration was 3.8 ± l.0 L/kg. Terminal elimination half-life was 1.0 ± 0.2 hours and 2.7 ± 2.8 hours after IV and SC administration, respectively. Mean residence time was 1.3 ± 0.3 hours and 3.6 ± 3.7 hours after IV and SC administration, respectively. Bioavailability was 64 ± 28%. Plasma concentrations after SC administration of SR buprenorphine were below the LLOQ in samples from 4 alpacas. There were no significant changes in pharmacodynamic parameters after buprenorphine administration. Alpacas exhibited mild behavioral changes after all treatments. CONCLUSIONS AND CLINICAL RELEVANCE Buprenorphine administration to healthy alpacas resulted in moderate bioavailability, rapid clearance, and a short half-life. Plasma concentrations were detectable in only 2 alpacas after SC administration of SR buprenorphine.

  17. Bioavailability of two manufacturers' sustained-release quinidine gluconate tablets at steady state.

    Science.gov (United States)

    Zinny, M A; Taggart, W V

    1984-01-01

    Steady-state bioavailability of sustained-release quinidine gluconate tablets manufactured by two companies was compared in a crossover study. The tablets were Quinaglute Dura-Tabs, manufactured by Berlex Laboratories, Inc., and generic quinidine gluconate tablets, manufactured by Bolar Pharmaceutical Company. Sixteen healthy male volunteers were given multiple doses of the two products in randomized sequence. Blood samples were obtained immediately before administration of the seventh dose (hour 72) and at 1, 2, 3, 4, 5, 6, 8, 10, and 12 hours after administration. Plasma samples were assayed for quinidine content by high-performance liquid chromatography. The tablets manufactured by Berlex provided statistically significantly higher plasma levels during the second half of the dosing interval (six to 12 hours postdose). A 29% difference in plasma levels was observed between the products at the end of the dosing interval. The Bolar quinidine gluconate tablets had a statistically significant lower area under the curve (AUC). The greatest difference in AUC occurred during the last six hours of the dosing period. The six- to 12-hour AUC for the Bolar tablets was 24% less than that for Berlex tablets. The generic tablets also achieved peak plasma level 31% sooner than did Quinaglute Dura-Tabs. The pharmacokinetic characteristics of the two products at steady state indicate that the Bolar quinidine gluconate tablet exhibited a more rapid onset of peak plasma levels and a more rapid decline to minimum plasma levels. In summary, the data from this multiple-dose study, performed using commercially available material, indicate that differences exist in pharmacokinetic performance of the products. However, the exact correlation between pharmacokinetic data and clinical effectiveness has not been established.

  18. The Use of Hibiscus esculentus (Okra) Gum in Sustaining the Release of Propranolol Hydrochloride in a Solid Oral Dosage Form

    Science.gov (United States)

    Noordin, Mohamed Ibrahim; Kadivar, Ali

    2014-01-01

    The effectiveness of Okra gum in sustaining the release of propranolol hydrochloride in a tablet was studied. Okra gum was extracted from the pods of Hibiscus esculentus using acetone as a drying agent. Dried Okra gum was made into powder form and its physical and chemical characteristics such as solubility, pH, moisture content, viscosity, morphology study using SEM, infrared study using FTIR, crystallinity study using XRD, and thermal study using DSC and TGA were carried out. The powder was used in the preparation of tablet using granulation and compression methods. Propranolol hydrochloride was used as a model drug and the activity of Okra gum as a binder was compared by preparing tablets using a synthetic and a semisynthetic binder which are hydroxylmethylpropyl cellulose (HPMC) and sodium alginate, respectively. Evaluation of drug release kinetics that was attained from dissolution studies showed that Okra gum retarded the release up to 24 hours and exhibited the longest release as compared to HPMC and sodium alginate. The tensile and crushing strength of tablets was also evaluated by conducting hardness and friability tests. Okra gum was observed to produce tablets with the highest hardness value and lowest friability. Hence, Okra gum was testified as an effective adjuvant to produce favourable sustained release tablets with strong tensile and crushing strength. PMID:24678512

  19. Formulation and pharmaceutical development of quetiapine fumarate sustained release matrix tablets using a QbD approach

    Directory of Open Access Journals (Sweden)

    Gavan Alexandru

    2017-03-01

    Full Text Available The main objective of the present study was to apply QbD methodology in the development of once-a-day sustained release quetiapine tablets. The quality target product profile (QTPP was defined after the pharmaceutical properties and kinetic release of the innovator product, Seroquel XR 200 mg. For the D-optimal experimental design, the level and ratio of matrix forming agents and the type of extragranular diluent were chosen as independent inputs, which represented critical formulation factors. The critical quality attributes (CQAs studied were the cumulative percentages of quetiapine released after certain time intervals. After the analysis of the experimental design, optimal formulas and the design space were defined. Optimal formulas demonstrated zero-order release kinetics and a dissolution profile similar to the innovator product, with f2 values of 74.53 and 83.74. It was concluded that the QbD approach allowed fast development of sustained release tablets with similar dissolution behavior as the innovator product.

  20. Original research paper. Formulation and pharmaceutical development of quetiapine fumarate sustained release matrix tablets using a QbD approach.

    Science.gov (United States)

    Gavan, Alexandru; Porfire, Alina; Marina, Cristina; Tomuta, Ioan

    2017-03-01

    The main objective of the present study was to apply QbD methodology in the development of once-a-day sustained release quetiapine tablets. The quality target product profile (QTPP) was defined after the pharmaceutical properties and kinetic release of the innovator product, Seroquel XR 200 mg. For the D-optimal experimental design, the level and ratio of matrix forming agents and the type of extragranular diluent were chosen as independent inputs, which represented critical formulation factors. The critical quality attributes (CQAs) studied were the cumulative percentages of quetiapine released after certain time intervals. After the analysis of the experimental design, optimal formulas and the design space were defined. Optimal formulas demonstrated zero-order release kinetics and a dissolution profile similar to the innovator product, with f2 values of 74.53 and 83.74. It was concluded that the QbD approach allowed fast development of sustained release tablets with similar dissolution behavior as the innovator product.

  1. Preparation of sustained-release coated particles by novel microencapsulation method using three-fluid nozzle spray drying technique.

    Science.gov (United States)

    Kondo, Keita; Niwa, Toshiyuki; Danjo, Kazumi

    2014-01-23

    We prepared sustained-release microcapsules using a three-fluid nozzle (3N) spray drying technique. The 3N has a unique, three-layered concentric structure composed of inner and outer liquid nozzles, and an outermost gas nozzle. Composite particles were prepared by spraying a drug suspension and an ethylcellulose solution via the inner and outer nozzles, respectively, and mixed at the nozzle tip (3N-PostMix). 3N-PostMix particles exhibited a corrugated surface and similar contact angles as ethylcellulose bulk, thus suggesting encapsulation with ethylcellulose, resulting in the achievement of sustained release. To investigate the microencapsulation process via this approach and its usability, methods through which the suspension and solution were sprayed separately via two of the four-fluid nozzle (4N) (4N-PostMix) and a mixture of the suspension and solution was sprayed via 3N (3N-PreMix) were used as references. It was found that 3N can obtain smaller particles than 4N. The results for contact angle and drug release corresponded, thus suggesting that 3N-PostMix particles are more effectively coated by ethylcellulose, and can achieve higher-level controlled release than 4N-PostMix particles, while 3N-PreMix particles are not encapsulated with pure ethylcellulose, leading to rapid release. This study demonstrated that the 3N spray drying technique is useful as a novel microencapsulation method. Copyright © 2013 Elsevier B.V. All rights reserved.

  2. The use of Hibiscus esculentus (Okra) gum in sustaining the release of propranolol hydrochloride in a solid oral dosage form.

    Science.gov (United States)

    Zaharuddin, Nurul Dhania; Noordin, Mohamed Ibrahim; Kadivar, Ali

    2014-01-01

    The effectiveness of Okra gum in sustaining the release of propranolol hydrochloride in a tablet was studied. Okra gum was extracted from the pods of Hibiscus esculentus using acetone as a drying agent. Dried Okra gum was made into powder form and its physical and chemical characteristics such as solubility, pH, moisture content, viscosity, morphology study using SEM, infrared study using FTIR, crystallinity study using XRD, and thermal study using DSC and TGA were carried out. The powder was used in the preparation of tablet using granulation and compression methods. Propranolol hydrochloride was used as a model drug and the activity of Okra gum as a binder was compared by preparing tablets using a synthetic and a semisynthetic binder which are hydroxylmethylpropyl cellulose (HPMC) and sodium alginate, respectively. Evaluation of drug release kinetics that was attained from dissolution studies showed that Okra gum retarded the release up to 24 hours and exhibited the longest release as compared to HPMC and sodium alginate. The tensile and crushing strength of tablets was also evaluated by conducting hardness and friability tests. Okra gum was observed to produce tablets with the highest hardness value and lowest friability. Hence, Okra gum was testified as an effective adjuvant to produce favourable sustained release tablets with strong tensile and crushing strength.

  3. Plasma concentrations of buprenorphine following a single subcutaneous administration of a sustained release formulation of buprenorphine in sheep

    OpenAIRE

    Zullian, Chiara; Lema, Pablo; Lavoie, Melissa; Dodelet-Devillers, Aurore; Beaudry, Francis; Vachon, Pascal

    2016-01-01

    The goal of the present study was to evaluate the potential use of slow release buprenorphine in sheep. Twelve adult female sheep (6 Dorset and 6 Suffolk, 12 months of age) were used for this project and were divided into 2 experimental groups (n = 6/group comprising 3 Dorset and 3 Suffolk sheep). Sustained release (SR) buprenorphine was administered subcutaneously in the scapular region at a concentration of 0.1 mg/kg body weight (BW) for group 1 and of 0.05 mg/kg BW for group 2. Following b...

  4. Butyrate-Loaded Chitosan/Hyaluronan Nanoparticles: A Suitable Tool for Sustained Inhibition of ROS Release by Activated Neutrophils

    DEFF Research Database (Denmark)

    Sacco, Pasquale; Decleva, Eva; Tentor, Fabio

    2017-01-01

    of neutrophil ROS production by free butyrate declines over time, that of butyrate-loaded chitosan/hyaluronan nanoparticles (B-NPs) is sustained. Additional valuable features of these nanoparticles are inherent ROS scavenger activity, resistance to cell internalization, and mucoadhesiveness. B-NPs appear...... that butyrate inhibits neutrophil ROS release in a dose and time-dependent fashion. Given the short half-life of butyrate, chitosan/hyaluronan nanoparticles are next designed and developed as controlled release carriers able to provide cells with a long-lasting supply of this SCFA. Notably, while the inhibition...

  5. Comparative study of sustained-release lipid microparticles and solid dispersions containing ibuprofen

    Directory of Open Access Journals (Sweden)

    Hugo Almeida

    2012-09-01

    Full Text Available Ibuprofen is one of the most important non-steroidal anti-inflammatory drugs used in the treatment of inflammatory diseases. In its pure state, ibuprofen presents poor physical and mechanical characteristics and its use in solid dosage forms needs the addition of excipients that improve these properties. The selection of the best excipients and the most suitable pharmaceutical dosage form to carry ibuprofen is very important for the industrial success of this drug. Given these factors, lipid microparticles and solid dispersions of ibuprofen with cetyl alcohol, stearic acid, and hydrogenated castor oil were prepared. These formulations were intended to improve the physical and mechanical characteristics and to sustain the release of this drug. Physical mixtures were also prepared with the same ingredients in similar proportions. The solid dispersions of ibuprofen/stearic acid and ibuprofen/hydrogenated castor oil showed the best flow characteristics compared with pure ibuprofen. Further, gelatin capsules filled with lipid microparticles and solid dispersions were submitted to dissolution tests in order to study the influence of the prepared systems in the release profiles of ibuprofen. Prolonged release of ibuprofen was achieved with the lipid microparticles and solid dispersions prepared with the different types of excipients.O ibuprofeno é um dos antiinflamatórios não esteróides mais utilizados no tratamento de patologias associadas a processos inflamatórios. Este fármaco, quando no seu estado puro, apresenta características físicas e mecânicas pouco satisfatórias e a sua utilização em formas sólidas só é possível se forem adicionados excipientes que permitam melhorar estas propriedades. A seleção dos excipientes ideais e da forma farmacêutica mais adequada para veicular o ibuprofeno é fundamental para o sucesso industrial deste fármaco. Tendo em conta estes fatores, prepararam-se micropartículas lipídicas e dispersões s

  6. Faecal blood loss during administration of acetylsalicylic acid, ketoprofen and two new ketoprofen sustained-release compounds.

    Science.gov (United States)

    Ranløv, P J; Nielsen, S P; Bärenholdt, O

    1983-01-01

    The influence of one week's treatment with acetylsalicylic acid, ketoprofen, ketoprofen sustained-release capsules (Biovail capsules), and ketoprofen sustained-release tablets (IBP tablet) on gastrointestinal bleeding was investigated in 41 healthy male volunteers by means of a radiochromium assay. The physiological faecal bleeding was 0.10 to 0.90 ml/day (99% confidence limits). It appeared that faecal bleeding during treatment with acetylsalicylic acid medication was greater than bleeding during medication with ketoprofen capsules in equipotent dosage, the latter being in turn causing significantly more bleeding than during medication with the newly developed Biovail capsules. The most modest faecal bleeding (0.8 ml/day) was seen with IBP tablets.

  7. Formulation and In-vitro Characterization of Sustained Release Matrix Type Ocular Timolol Maleate Mini-Tablet

    OpenAIRE

    Mortazavi, Seyed Alireza; Jafariazar, Zahra; Ghadjahani, Yasaman; Mahmoodi, Hoda; Mehtarpour, Farzaneh

    2014-01-01

    The purpose of this study was preparation and evaluation of sustained release matrix type ocular mini-tablets of timolol maleate, as a potential formulation for the treatment of glaucoma. Following the initial studies on timolol maleate powder, it was formulated into ocular mini-tablets. The polymers investigated in this study included cellulose derivatives (HEC, CMC, EC) and Carbopol 971P. Mannitol was used as the solubilizing agent and magnesium stearate as the lubricant. Mini-tablets were ...

  8. Evaluation of gum mastic (Pistacia lentiscus) as a microencapsulating and matrix forming material for sustained drug release

    OpenAIRE

    Dinesh M. Morkhade

    2017-01-01

    In this study, a natural gum mastic was evaluated as a microencapsulating and matrix-forming material for sustained drug release. Mastic was characterized for its physicochemical properties. Microparticles were prepared by oil-in-oil solvent evaporation method. Matrix tablets were prepared by wet and melt granulation techniques. Diclofenac sodium (DFS) and diltiazem hydrochloride (DLTZ) were used as model drugs. Mastic produced discrete and spherical microspheres with DLTZ and microcapsules w...

  9. Sustained-release dexamethasone intravitreal implant in juvenile idiopathic arthritis-related uveitis.

    Science.gov (United States)

    Pichi, Francesco; Nucci, Paolo; Baynes, Kimberly; Lowder, Careen Y; Srivastava, Sunil K

    2017-02-01

    The purpose of this study is to review the results of treatment of juvenile idiopathic arthritis-related uveitis with the use of intravitreal dexamethasone implant. Sixteen eyes with Juvenile idiopathic arthritis (JIA)-associated uveitis received intravitreal dexamethasone implant to treat recalcitrant anterior segment inflammation (43.7 %), chronic macular edema (6.2 %), or a combination of both (50 %). One month after injection, mean visual acuity had improvement to 39.6 ± 11 ETDRS letters (p < 0.001). Mean AC cells measure at 1 month was 0.79 and 0.75 at 3 months. One month after injection, there was a significant reduction of central retinal thickness (CRT) to 342.4 ± 79.3 µm (p < 0.01). One month after the second implant, 11 eyes (91.6 %) achieved improved activity of the anterior uveitis, and mean best-corrected visual acuity improved to 44.6 ± 8.1 ETDRS letters (p < 0.01). At 1 month after the second injection, 4/5 eyes had resolution of macular edema with CRT of 250.4 ± 13.7 µm (p < 0.01). Of the 16 eyes, 12 eyes received a second injection at mean of 7.5 ± 3.1 months after the first treatment, and 5 eyes received a third Ozurdex injection on average 7 ± 4.6 months after the second injection. Of the 16 eyes, five eyes were pseudophakic prior to injection. Of the remaining 11 eyes, 8 (73 %) developed worsening posterior subcapsular cataract at a mean of 7.3 ± 1.2 months after the first injection. After the first injection, only one eye required topical antiglaucoma therapy with maximum pressure of 25 mmHg. In patients with recalcitrant JIA-associated active uveitis, injection of sustained-release dexamethasone can achieve control of anterior inflammation and resolution of macular edema.

  10. Formulation of novel sustained release rifampicin-loaded solid lipid microparticles based on structured lipid matrices from Moringa oleifera.

    Science.gov (United States)

    Onyishi, Ikechukwu V; Chime, Salome A; Ogudiegwu, Echezona O

    2015-01-01

    To formulate sustained release rifampicin-loaded solid lipid microparticles (SLMs) using structured lipid matrices based on Moringa oil (MO) and Phospholipon 90G (P90G). Rifampicin-loaded and unloaded SLMs were formulated by melt homogenization and characterized in terms of particle morphology and size, percentage drug content (PDC), pH stability, stability in simulated gastric fluid (SGF, pH 1.2), minimum inhibitory concentration (MIC) and in vitro release. In vivo release was studied in Wistar rats. Rifampicin-loaded SLMs had particle size range of 32.50 ± 2.10 to 34.0 ± 8.40 μm, highest PDC of 87.6% and showed stable pH. SLMs had good sustained release properties with about 77.1% release at 12 h in phosphate buffer (pH 6.8) and 80.3% drug release at 12 h in simulated intestinal fluid (SIF, pH 7.4). SLMs exhibited 48.51% degradation of rifampicin in SGF at 3 h, while rifampicin pure sample had 95.5% degradation. Formulations exhibited MIC range of 0.781 to 1.562, 31.25 to 62.5 and 6.25 to 12.5 μg/ml against Salmonella typhi, Escherichia coli, and Bacillus subtilis respectively and had higher in vivo absorption than the reference rifampicin (p < 0.05). Rifampicin-loaded SLMs could be used once daily for the treatment tuberculosis.

  11. Determination of solid state characteristics of spray-congealed Ibuprofen solid lipid microparticles and their impact on sustaining drug release.

    Science.gov (United States)

    Wong, Priscilla Chui Hong; Heng, Paul Wan Sia; Chan, Lai Wah

    2015-05-04

    This study was used to find solid state characteristics of ibuprofen loaded spray-congealed solid lipid microparticles (SLMs) by employing simple lipids as matrices, with or without polymeric additives, and the impact of solid drug-matrix miscibility on sustaining drug release. Solid miscibility of ibuprofen with two lipids, cetyl alcohol (CA) and stearic acid (SA), were investigated using differential scanning calorimetry (DSC). SLMs containing 20% w/w ibuprofen with or without polymeric additives, PVP/VA and EC, were produced by spray congealing, and the resultant microparticles were subjected to visual examination by scanning electron microscopy (SEM), thermal analysis using DSC, and hot-stage microscopy. Intermolecular interactions between lipids and drug as well as additives were investigated by Fourier-transformed infrared spectroscopy (FTIR) and nuclear magnetic resonance spectroscopy (NMR). X-ray diffractometry (XRD) was utilized to study polymorphic changes of drug and matrix over the course of a year. Ibuprofen was found to depress the melting points of CA and SA in a colligative manner, reaching maximum solubility at 10% w/w and 30% w/w for CA and SA, respectively. Drug encapsulation efficiencies and yields of spray-congealed SLMs containing 20% w/w ibuprofen were consistently high for both lipid matrices. CA and SA were found to adopt their stable γ- and β-polymorphs, respectively, immediately after spray congealing. The spray congealing process resulted in ibuprofen adopting an amorphous or poorly crystalline state, with no further changes over the course of a year. SEM, DSC, and hot stage microscope studies on the SLMs confirmed the formation of a solid dispersion between ibuprofen and CA and a solid solution between ibuprofen and SA. SA was found to sustain the release of ibuprofen significantly better than CA. PVP/VA and EC showed some interactions with CA, which led to an expansion of unit cell dimensions of CA upon spray congealing, whereas they

  12. In-vitro trials to ascertain sustained release efficacy of assembly pheromone micro particles for the control of brown dog tick, Rhipicephalus sanguineus.

    Science.gov (United States)

    Bhoopathy, Dhivya; Bhaskaran Ravi, Latha

    2017-12-01

    Sustained release micro particles were prepared incorporating assembly pheromone and deltamethrin. Two natural polymers, namely, chitosan and calcium alginate and a synthetic polymer, poly-ε-caprolactone were used for encapsulating the assembly pheromone-acaricide combination. The micro particles were subjected to in vitro evaluation freshly after preparation and then at monthly intervals to assess their sustained release efficacy. The response of the unfed stages of dog tick, Rhipicephalus sanguineus to fresh and aged micro particles was assessed and results were recorded. The micro particles were found to release assembly pheromone in a sustained manner up to 2 months of study period.

  13. Pore size is a critical parameter for obtaining sustained protein release from electrochemically synthesized mesoporous silicon microparticles

    Directory of Open Access Journals (Sweden)

    Ester L. Pastor

    2015-10-01

    Full Text Available Mesoporous silicon has become a material of high interest for drug delivery due to its outstanding internal surface area and inherent biodegradability. We have previously reported the preparation of mesoporous silicon microparticles (MS-MPs synthesized by an advantageous electrochemical method, and showed that due to their inner structure they can adsorb proteins in amounts exceeding the mass of the carrier itself. Protein release from these MS-MPs showed low burst effect and fast delivery kinetics with complete release in a few hours. In this work, we explored if tailoring the size of the inner pores of the particles would retard the protein release process. To address this hypothesis, three new MS-MPs prototypes were prepared by electrochemical synthesis, and the resulting carriers were characterized for morphology, particle size, and pore structure. All MS-MP prototypes had 90 µm mean particle size, but depending on the current density applied for synthesis, pore size changed between 5 and 13 nm. The model protein α-chymotrypsinogen was loaded into MS-MPs by adsorption and solvent evaporation. In the subsequent release experiments, no burst release of the protein was detected for any prototype. However, prototypes with larger pores (>10 nm reached 100% release in 24–48 h, whereas prototypes with small mesopores (<6 nm still retained most of their cargo after 96 h. MS-MPs with ∼6 nm pores were loaded with the osteogenic factor BMP7, and sustained release of this protein for up to two weeks was achieved. In conclusion, our results confirm that tailoring pore size can modify protein release from MS-MPs, and that prototypes with potential therapeutic utility for regional delivery of osteogenic factors can be prepared by convenient techniques.

  14. Development and characterization of gastroretentive sustained-release formulation by combination of swelling and mucoadhesive approach: a mechanistic study

    Directory of Open Access Journals (Sweden)

    Sankar R

    2013-12-01

    Full Text Available R Sankar,1 Subheet Kumar Jain1,2 1Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, Punjab, India; 2Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, Punjab, India Background: Acyclovir has pharmacokinetic limitations, including poor oral bioavailability of 15%–30%, high variability, and short elimination half-life of 2.3 hours. These limitations necessitate frequent administration of acyclovir, up to five times daily, leading to poor patient compliance, which in turn leads to a reduction in therapeutic efficacy and development of resistance. Methods: A gastroretentive sustained-release (GR formulation of acyclovir, based on a combination of swelling and mucoadhesive mechanisms, has been developed. Composition has been optimized after evaluation of different polymers, carbomer, polyethylene oxide, and sodium alginate alone and/or in combination. GR formulations were characterized for in-process quality-control tests, drug release and release rate kinetics, similarity factor analysis, swelling index, and matrix erosion. Results: A formulation containing a combination of carbomer and polyethylene oxide had the highest similarity of drug release compared with a target drug-release profile obtained by pharmacokinetic simulations. The measurement of mucoadhesive strength, carried out with a texture analyzer, showed that the mucoadhesive strength of the GR formulation was significantly higher than that of the immediate-release (IR tablet. The optimized GR formulation was found to be retained in the upper part of the gastrointestinal tract for 480 minutes; the IR tablet was retained for only 90 minutes as measured using a gastrointestinal retention study in albino rabbits. The GR formulation was also found to maintain more sustained plasma concentrations than the IR tablet. Mean residence time of the GR formulation was 7 hours versus 3.3 hours for the IR formulation. The relative

  15. Bimatoprost-loaded ocular inserts as sustained release drug delivery systems for glaucoma treatment: in vitro and in vivo evaluation.

    Directory of Open Access Journals (Sweden)

    Juçara Ribeiro Franca

    Full Text Available The purpose of the present study was to develop and assess a novel sustained-release drug delivery system of Bimatoprost (BIM. Chitosan polymeric inserts were prepared using the solvent casting method and characterized by swelling studies, infrared spectroscopy, differential scanning calorimetry, drug content, scanning electron microscopy and in vitro drug release. Biodistribution of 99mTc-BIM eye drops and 99mTc-BIM-loaded inserts, after ocular administration in Wistar rats, was accessed by ex vivo radiation counting. The inserts were evaluated for their therapeutic efficacy in glaucomatous Wistar rats. Glaucoma was induced by weekly intracameral injection of hyaluronic acid. BIM-loaded inserts (equivalent to 9.0 µg BIM were administered once into conjunctival sac, after ocular hypertension confirmation. BIM eye drop was topically instilled in a second group of glaucomatous rats for 15 days days, while placebo inserts were administered once in a third group. An untreated glaucomatous group was used as control. Intraocular pressure (IOP was monitored for four consecutive weeks after treatment began. At the end of the experiment, retinal ganglion cells and optic nerve head cupping were evaluated in the histological eye sections. Characterization results revealed that the drug physically interacted, but did not chemically react with the polymeric matrix. Inserts sustainedly released BIM in vitro during 8 hours. Biodistribution studies showed that the amount of 99mTc-BIM that remained in the eye was significantly lower after eye drop instillation than after chitosan insert implantation. BIM-loaded inserts lowered IOP for 4 weeks, after one application, while IOP values remained significantly high for the placebo and untreated groups. Eye drops were only effective during the daily treatment period. IOP results were reflected in RGC counting and optic nerve head cupping damage. BIM-loaded inserts provided sustained release of BIM and seem to be a

  16. The impact of selected preparations of trace elements - magnesium, potassium, calcium, and zinc on the release of diclofenac sodium from enteric coated tablets and from sustained release capsules.

    Science.gov (United States)

    Biernat, Paweł; Musiał, Witold; Gosławska, Dorota; Pluta, Janusz

    2014-01-01

    In an aging society, many patients require long-term treatment. This fact is associated clearly with the simultaneous occurrence of lifestyle diseases such as hypertension, diabetes, and even osteoarthritis. Concomitant medications, which are a common practice, pose a major threat of an interaction between these drugs. Very popular now "fast way of life" that makes people have less and less time to prepare well-balanced meals of high nutritional value. The result of this lifestyle is an increased need for supplementation preparations necessary vitamins and minerals. Given the wide availability of dietary supplements (shops, kiosks, petrol stations) raises the question about the possibility of an interaction between the uncontrolled intake of dietary supplements and medications received in the most common diseases of civilization. The aim of this study was to investigate the effect of the most important minerals (magnesium, potassium, calcium, zinc) contained in the popular nutritional supplements, the release also often used as an anti-pain, anti-inflammatory, diclofenac sodium from the different formulations. Among the many as sodium diclofenac selected two most common: film-coated tablets and sustained release capsules. The study showed a significant effect of minerals on the release of diclofenac sodium and differences that impact, depending on the test form of the drug.

  17. Sustained release of adipose-derived stem cells by thermosensitive chitosan/gelatin hydrogel for therapeutic angiogenesis.

    Science.gov (United States)

    Cheng, Nai-Chen; Lin, Wei-Jhih; Ling, Thai-Yen; Young, Tai-Horng

    2017-03-15

    Adipose-derived stem cells (ASCs) secrete several angiogenic growth factors and can be applied to treat ischemic tissue. However, transplantation of dissociated ASCs has frequently resulted in rapid cell death. Therefore, we aimed to develop a thermosensitive chitosan/gelatin hydrogel that is capable of ASC sustained release for therapeutic angiogenesis. By blending gelatin in the chitosan thermosensitive hydrogel, we significantly enhanced the viability of the encapsulated ASCs. During in vitro culturing, the gradual degradation of gelatin led to sustained release of ASCs from the chitosan/gelatin hydrogel. In vitro wound healing assays revealed significantly faster cell migration by co-culturing fibroblasts with ASCs encapsulated in chitosan/gelatin hydrogel compared to pure chitosan hydrogels. Additionally, significantly higher concentrations of vascular endothelial growth factor were found in the supernatant of ASC-encapsulated chitosan/gelatin hydrogels. Co-culturing SVEC4-10 endothelial cells with ASC-encapsulated chitosan/gelatin hydrogels resulted in significantly more tube-like structures, indicating the hydrogel's potential in promoting angiogenesis. Chick embryo chorioallantoic membrane assay and mice wound healing model showed significantly higher capillary density after applying ASC-encapsulated chitosan/gelatin hydrogel. Relative to ASC alone or ASC-encapsulated chitosan hydrogel, more ASCs were also found in the wound tissue on post-wounding day 5 after applying ASC-encapsulated chitosan/gelatin hydrogel. Therefore, chitosan/gelatin thermosensitive hydrogels not only maintain ASC survival, they also enable sustained release of ASCs for therapeutic angiogenesis applications, thereby exhibiting great clinical potential in treating ischemic diseases. Adipose-derived stem cells (ASCs) exhibit great potential to treat ischemic diseases. However, poor delivery methods lead to low cellular survival or dispersal of cells from target sites. In this study, we

  18. Development of molecularly imprinted polymer as sustain release drug carrier for propranolol HCL.

    Science.gov (United States)

    Barde, Laxmikant N; Ghule, Mahesh M; Roy, Arghya A; Mathur, Vijay B; Shivhare, Umesh D

    2013-08-01

    Applications of molecularly imprinted polymer (MIPs), is rapidly increasing, especially in the drug delivery field. Molecularly imprinted polymers are the molecular traps, which can entrap the specific molecule and also control its release. Polymer complexes were prepared with and without propranolol HCl as templates, MAA (methacrylic acid) as monomer and EGDMA (ethyleneglycol dimethacrylate) as crosslinker by solvent polymerization technique. Drug release pattern from these polymer complexes were compared and maximum drug release in 12 h was consider to optimize the ratio of MAA and EGDMA. Since, the maximum propranolol HCl release from polymer complex was low (62.15%) in optimized batch, inclusion complex of drug with β-cyclodextrin were prepared for the higher drug release (80.32%). The selected polymer complexes were treated with methanol for complete removal of the drug to form MIPs. These MIPs were reloaded with the drug and subjected for drug release. The release patterns from reloaded MIP's were observed to be slightly quicker than their corresponding MIP's.

  19. A poly({epsilon}-caprolactone) device for sustained release of an anti-glaucoma drug

    Energy Technology Data Exchange (ETDEWEB)

    Natu, Madalina V; De Sousa, HermInio C; Gil, M H [Department of Chemical Engineering, University of Coimbra, Polo II, Pinhal de Marrocos, 3030-290, Coimbra (Portugal); Gaspar, Manuel N; Fontes Ribeiro, Carlos A [Institute of Pharmacology and Experimental Therapeutics, University of Coimbra, Azinhaga de Santa Comba, Celas, 3000-354, Coimbra (Portugal); Correia, IlIdio J; Silva, Daniela, E-mail: hgil@eq.uc.pt [Centro de Investigacao em Ciencias da Saude, Faculdade de Ciencias da Saude, Universidade da Beira Interior, Covilha (Portugal)

    2011-04-15

    Implantable dorzolamide-loaded discs were prepared by blending poly({epsilon}-caprolactone), PCL, with poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide), Lu. By blending, crystallinity, water uptake and mass loss were modified relative to the pure polymers. Burst was diminished by coating the discs with a PCL shell. All samples presented burst release except PCL-coated samples that showed controlled release during 18 days. For PCL-coated samples, barrier control of diffusion coupled with partition control from the core slowed down the release, while for 50/50 Lu/PCL-coated samples, the enhancement in the porosity of the core diminished partition control of drug release. Nonlinear regression analysis suggested that a degradation model fully describes the release curve considering a triphasic release mechanism: the instantaneous diffusion (burst), diffusion and polymer degradation stages. The MTT test indicated that the materials are not cytotoxic for corneal endothelial cells. A good in vitro-in vivo correlation was obtained, with similar amounts of drug released in vitro and in vivo. The discs decreased intraocular pressure (IOP) in normotensive rabbit eyes by 13.0% during 10 days for PCL-coated and by 13.0% during 4 days for 50/50 Lu/PCL-coated samples. The percentages of IOP decrease are similar to those obtained by dorzolamide eyedrop instillation (11.0%).

  20. Nanostructure of liquid crystalline matrix determines in vitro sustained release and in vivo oral absorption kinetics for hydrophilic model drugs.

    Science.gov (United States)

    Lee, Kathy W Y; Nguyen, Tri-Hung; Hanley, Tracey; Boyd, Ben J

    2009-01-05

    Nanostructured lipid-based liquid crystalline systems have been proposed as sustained oral drug delivery systems, but the interplay between their intrinsic release rates, susceptibility to digestive processes, and the manner in which these effects impact on their application in vivo, are not well understood. In this study, two different bicontinuous cubic phases, prepared from glyceryl monooleate and phytantriol, and a reversed hexagonal phase formed by addition of a small amount of vitamin E to phytantriol (Q(II GMO), Q(II PHYT) and H(II PHYT+VitEA), respectively) were prepared. The release kinetics for a number of model hydrophilic drugs with increasing molecular weights (glucose, Allura Red and FITC-dextrans) was determined in in vitro release experiments. Diffusion-controlled release was observed in all cases as anticipated from previous studies with liquid crystalline systems, and it was discovered that the release rates of each drug decreased as the matrix was changed from Q(II GMO) to Q(II PHYT) to H(II PHYT+VitEA). Formulations containing (14)C-glucose, utilized as a rapidly absorbed marker of drug release, were then orally administered to rats to determine the relative in vivo absorption rates from the different formulations. The results showed a trend by which the rate of absorption of (14)C-glucose followed that observed in the corresponding in vitro release studies, providing the first indication that the nanostructure of these materials may provide the ability to tailor the absorption kinetics of hydrophilic drugs in vivo, and hence form the basis of a new drug delivery system.

  1. Doc2b synchronizes secretion from chromaffin cells by stimulating fast and inhibiting sustained release

    DEFF Research Database (Denmark)

    da Silva Pinheiro, Paulo César; de Wit, Heidi; Walter, Alexander M

    2013-01-01

    Synaptotagmin-1 and -7 constitute the main calcium sensors mediating SNARE-dependent exocytosis in mouse chromaffin cells, but the role of a closely related calcium-binding protein, Doc2b, remains enigmatic. We investigated its role in chromaffin cells using Doc2b knock-out mice and high temporal...... resolution measurements of exocytosis. We found that the calcium dependence of vesicle priming and release triggering remained unchanged, ruling out an obligatory role for Doc2b in those processes. However, in the absence of Doc2b, release was shifted from the readily releasable pool to the subsequent...

  2. Sustained-release microspheres of amifostine for improved radio-protection, patient compliance, and reduced side effects.

    Science.gov (United States)

    Wu, Hong-Yu; Hu, Zhen-Hua; Jin, Tuo

    2016-11-01

    A biweekly administration of sustained-release microsphere dosage form of amifostine, a radioprotective drug used in radiotherapy, was performed to examine the feasibility to minimize injection frequency and blood concentration-associated side effects. Model animal trials indicated that this subcutaneously injecting microspheres, 50-100 μm in diameter, achieved bi-weekly prolonged radio-protective efficacy and, at the same time, significantly reduced skin irritation than the solution form of amifostine given by the same administration route. In addition, the hypertension associated with blood concentration of amifostine was not observed in the drug-treated rats. The animals given the amifostine microspheres and amifostine showed significantly differences in white blood cell, red blood cell, hematocrit, hemoglobin and spleen tissue histopathology after exposed under a cobalt-60 γ-radiation at a dose rate of 1.0 Gy/min for 6 min. The in vitro release profile of amifostine from the micropsheres showed a minor initial burst (less than 20% of total drug loading in the first day of administration), consisting with the side effects observations. The results suggest that amifostine encapsulated in sustained-release microspheres may be an ideal dosage form for prolonged radio-protective efficacy and improved patient compliance.

  3. Development of Denticap, a matrix based sustained release formulation for treatment of toothache, dental infection and other gum problem.

    Science.gov (United States)

    Mukherjee, Biswajit; Roy, Gopa; Ghosh, Soma

    2009-04-01

    Toothache is a serious problem worldwide. To give relief from this intolerable toothache, doctors prescribe painkillers along with antibiotics. Most of the painkillers, if not all, produce hyperacidity and gastric irritation upon oral administration. Oral antibiotics have slow onset of action and undergo hepatic "first-pass" effect. Moreover, available dental formulations are mostly liquid and last only few hours upon application, before being washed out by saliva. To overcome the above-mentioned problems, a soft polymeric mold containing antibiotic and analgesic drugs and having an appropriate consistency to adhere to the tooth, was developed for sustained drug release to provide better relief in dental patients. Eudragit L 100-55, carbopol 971 P, gum karaya powder and ethyl cellulose were used to prepare the mold "Denticaps" containing Lidocaine hydrochloride and Amoxicillin trihydrate individually and in combination, by mixing and solvent evaporation technique. Different physicochemical characterization studies such as mucoadhesion test, water absorption capacity and swelling index were carried out. In vitro drug release studies showed sustained release of Lidocaine hydrochloride and Amoxicillin trihydrate in simulated saliva for 24 h. Further studies are warranted to succeed with these formulations in humans. Upon success, this type of dosage form may open up new avenues towards dentistry.

  4. High-Amylose Sodium Carboxymethyl Starch Matrices: Development and Characterization of Tramadol Hydrochloride Sustained-Release Tablets for Oral Administration

    Science.gov (United States)

    Nabais, Teresa; Leclair, Grégoire

    2014-01-01

    Substituted amylose (SA) polymers were produced from high-amylose corn starch by etherification of its hydroxyl groups with chloroacetate. Amorphous high-amylose sodium carboxymethyl starch (HASCA), the resulting SA polymer, was spray-dried to obtain an excipient (SD HASCA) with optimal binding and sustained-release (SR) properties. Tablets containing different percentages of SD HASCA and tramadol hydrochloride were produced by direct compression and evaluated for dissolution. Once-daily and twice-daily SD HASCA tablets containing two common dosages of tramadol hydrochloride (100 mg and 200 mg), a freely water-soluble drug, were successfully developed. These SR formulations presented high crushing forces, which facilitate further tablet processing and handling. When exposed to both a pH gradient simulating the pH variations through the gastrointestinal tract and a 40% ethanol medium, a very rigid gel formed progressively at the surface of the tablets providing controlled drug-release properties. These properties indicated that SD HASCA was a promising and robust excipient for oral, sustained drug-release, which may possibly minimize the likelihood of dose dumping and consequent adverse effects, even in the case of coadministration with alcohol. PMID:25006518

  5. Sustained release of antibiotic complexed by multivalent ion: in vitro and in vivo study for the treatment of peritonitis.

    Science.gov (United States)

    Na, Seung Yeon; Oh, Se Heang; Kim, Tae Ho; Yoon, Jin A; Lee, In Soo; Lee, Jin Ho

    2014-12-10

    The main aims of this study are (i) the development of an antibiotic complexed with multivalent ion, which can allow sustained release of the antibiotic without any additional matrix or difficult process and (ii) the feasibility study of the ion-complexed antibiotic as a therapeutic technique for peritonitis treatment. An ion-complexed antibiotic is prepared by simple mixing of two aqueous solutions containing an ionized (water-soluble) drug (tetracycline) and a multivalent counter ionic compound. The ion-complexed antibiotic shows a continuous release of the antibiotic up to 21 days, and thus prolonged anti-bacterial effect by gradual ionic exchange between the multivalent ions in the complex and same-charged monovalent ions in surrounding medium. From the in vivo animal study using a cecum perforated peritonitis mouse model, the ion-complexed antibiotic group shows sufficient anti-bacterial effect and thus effectively treat the peritonitis because of the extermination of the contaminated enteric bacteria in the peritoneum during wound healing of injury cecum (by the sustained release of antibiotic from the ion complex). These results suggest that the ion-complexed antibiotic system may be promising for the effective treatment of the peritonitis caused by frequent gastrointestinal defect in clinical fields. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. Perforator-Based Interposition Flaps for Sustainable Scar Contracture Release: A Versatile, Practical, and Safe Technique

    NARCIS (Netherlands)

    Verhaegen, Pauline D. H. M.; Stekelenburg, Carlijn M.; van Trier, Antoine J. M.; Schade, Frank B.; van Zuijlen, Paul P. M.

    2011-01-01

    Background: Problematic scar contractures are frequently observed following extensive (burn) wounds. In this study, the authors investigated the applicability of islanded and nonislanded perforator-based interposition flaps as a technique for release of scar contracture. Methods: Patients requiring

  7. Optimization of sustained-release propranolol dosage form using factorial design and response surface methodology.

    Science.gov (United States)

    Huang, Yaw-Bin; Tsai, Yi-Hung; Yang, Wan-Chiech; Chang, Jui-Sheng; Wu, Pao-Chu

    2004-10-01

    The purpose of this study was to develop propranolol extended release formulations containing hydroxypropylmethylcellulose (HPMC). The results indicate that the drug release from the tablet form containing a high amount of HPMC was incomplete, and avicel addition could increase the release percent at a later stage. In order to readily obtain an optimal formulation, response surface methodology and multiple response optimization utilizing a quadratic polynomial equation was used. The model formulations were prepared according to a factorial design. The effects of causal factors including the HPMC/drug ratio (X1) and avicel level (X2), on drug release were also measured. The drug release percentage at 1.5, 4, 8, 14 and 24 h were the target response and were restricted to not more than 25%, 35-50%, 55-70%, 75-90%, and 95-110%, respectively. The results showed that the optimized formulation provided a dissolution pattern equivalent to the predicted curve, which indicated that the optimal formulation could be obtained using response surface methodology. The mechanism of drug release from HMPC matrices tablets followed quasi-Fickian diffusion.

  8. Sustained release of aspirin and vitamin C from titanium nanotubes: An experimental and stimulation study.

    Science.gov (United States)

    Yang, Weihu; Deng, Conghui; Liu, Peng; Hu, Yan; Luo, Zhong; Cai, Kaiyong

    2016-07-01

    Anodization is a promising method to change the topography and wettability of titanium (Ti) implant. The formed TiO2 nanotubes (TiNTs) arrays could enhance the biological properties of Ti implants. In this study, to investigate the possibility of TiNTs arrays on a Ti implant surface as nano-reservoirs for small molecular drugs when using in orthopedic and dental prosthesis, TiNTs on a Ti implant surface were prepared. Then, aspirin and/or vitamin C were loaded into TiNTs as model drugs. Meanwhile, low molecular weight polylactic acid (PLA, Mw=3000) was synthesized and loaded alternately along with aspirin or vitamin C. The release rates of aspirin and vitamin C with/or without PLA loading were investigated by using a UV-Vis spectrometer. The results showed that when loading without PLA, drugs released quickly with presence of burst release. However, when loading with PLA, the cumulative release duration of aspirin and vitamin C was prolonged to over 240h. Molecular dynamics (MD) simulation and dissipative particle dynamics (DPD) simulation results proved that when loading with PLA, PLA molecules aggregated gradually and formed clusters or micelles in these nanotubes. Meanwhile, drug molecules were captured and distributed inside the PLA matrix, which retarding the release of drugs. Only when PLA micelles degrade gradually in body fluid, drugs could be released slowly from nanotubes. These knowledge laid ground basis for the following biological experiments. Copyright © 2016. Published by Elsevier B.V.

  9. Local sustained-release delivery systems of the antibiofilm agent thiazolidinedione-8 for prevention of catheter-associated urinary tract infections.

    Science.gov (United States)

    Shenderovich, Julia; Feldman, Mark; Kirmayer, David; Al-Quntar, Abed; Steinberg, Doron; Lavy, Eran; Friedman, Michael

    2015-05-15

    Thiazolidinedione-8 (TZD-8) is an anti-quorum-sensing molecule that has the potential to effectively prevent catheter-associated urinary tract infections, a major healthcare challenge. Sustained-release drug-delivery systems can enhance drugs' therapeutic potential, by maintaining their therapeutic level and reducing their side effects. Varnishes for sustained release of TZD-8 based on ethylcellulose or ammonio methacrylate copolymer type A (Eudragit(®) RL) were developed. The main factors affecting release rate were found to be film thickness and presence of a hydrophilic or swellable polymer in the matrix. The release mechanism of ethylcellulose-based systems matched the Higuchi model. Selected varnishes were retained on catheters for at least 8 days. Sustained-release delivery systems of TZD-8 were active against Candida albicans biofilms. The present study demonstrates promising results en route to developing applications for the prevention of catheter-associated infections. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. Pharmacokinetics of a Sustained-release Formulation of Meloxicam After Subcutaneous Administration to Hispaniolan Amazon Parrots (Amazona ventralis).

    Science.gov (United States)

    Guzman, David Sanchez-Migallon; Court, Michael H; Zhu, Zhaohui; Summa, Noémie; Paul-Murphy, Joanne R

    2017-09-01

    Meloxicam has been shown to have a safe and favorable pharmacodynamic profile with individual variability in Hispaniolan Amazon parrots (Amazona ventralis). In the current study, we determined the pharmacokinetics of a sustained-release formulation of meloxicam after subcutaneous administration to Hispaniolan Amazon parrots. Twelve healthy adult parrots, 6 males and 6 females, were used in the study. Blood samples were collected before (time 0) and at 0.5, 1, 2, 6, 12, 24, 48, 72, 96, and 120 hours after a single dose of the sustained-release meloxicam formulation (3 mg/kg SC). Plasma meloxicam concentrations were measured by high-pressure liquid chromatography. Pharmacokinetic parameters were determined by noncompartmental analysis. Plasma concentrations reached a mean Cmax of 23.4 μg/mL (range, 14.7-46.0 μg/mL) at 1.8 hours (range, 0.5-6 hours), with a terminal half-life of 7.4 hours (range, 1.4-40.9 hours). Individual variation was noticeable, such that some parrots (4 of 12 birds) had very low plasma meloxicam concentrations, similar to the high variability reported in a previous pharmacokinetic study of the standard meloxicam formulation in the same group of birds. Two birds developed small self-resolving scabs at the injection site. On the basis of these results, the sustained-release meloxicam formulation could be administered every 12 to 96 hours in Hispaniolan Amazon parrots to manage pain. Because of these highly variable results, the use of this formulation in this species cannot be recommended until further pharmacokinetic, safety, and pharmacogenomic evaluations are performed to establish accurate dosing recommendations and to understand the high pharmacokinetic variability.

  11. Synthetic geopolymers for controlled delivery of oxycodone: adjustable and nanostructured porosity enables tunable and sustained drug release.

    Science.gov (United States)

    Forsgren, Johan; Pedersen, Christian; Strømme, Maria; Engqvist, Håkan

    2011-03-15

    In this article we for the first time present a fully synthetic mesoporous geopolymer drug carrier for controlled release of opioids. Nanoparticulate precursor powders with different Al/Si-ratios were synthesized by a sol-gel route and used in the preparation of different geopolymers, which could be structurally tailored by adjusting the Al/Si-ratio and the curing temperatures. In particular, it was shown that the pore sizes of the geopolymers decreased with increasing Al/Si ratio and that completely mesoporous geopolymers could be produced from precursor particles with the Al/Si ratio 2:1. The mesoporosity was shown to be associated with a sustained and linear in vitro release profile of the opioid oxycodone. A clinically relevant release period of about 12 h was obtained by adjusting the size of the pellets. The easily fabricated and tunable geopolymers presented in this study constitute a novel approach in the development of controlled release formulations, not only for opioids, but whenever the clinical indication is best treated with a constant supply of drugs and when the mechanical stability of the delivery vehicle is crucial.

  12. Synthetic Geopolymers for Controlled Delivery of Oxycodone: Adjustable and Nanostructured Porosity Enables Tunable and Sustained Drug Release

    Science.gov (United States)

    Forsgren, Johan; Pedersen, Christian; Strømme, Maria; Engqvist, Håkan

    2011-01-01

    In this article we for the first time present a fully synthetic mesoporous geopolymer drug carrier for controlled release of opioids. Nanoparticulate precursor powders with different Al/Si-ratios were synthesized by a sol-gel route and used in the preparation of different geopolymers, which could be structurally tailored by adjusting the Al/Si-ratio and the curing temperatures. In particular, it was shown that the pore sizes of the geopolymers decreased with increasing Al/Si ratio and that completely mesoporous geopolymers could be produced from precursor particles with the Al/Si ratio 2∶1. The mesoporosity was shown to be associated with a sustained and linear in vitro release profile of the opioid oxycodone. A clinically relevant release period of about 12 h was obtained by adjusting the size of the pellets. The easily fabricated and tunable geopolymers presented in this study constitute a novel approach in the development of controlled release formulations, not only for opioids, but whenever the clinical indication is best treated with a constant supply of drugs and when the mechanical stability of the delivery vehicle is crucial. PMID:21423616

  13. Synthetic geopolymers for controlled delivery of oxycodone: adjustable and nanostructured porosity enables tunable and sustained drug release.

    Directory of Open Access Journals (Sweden)

    Johan Forsgren

    Full Text Available In this article we for the first time present a fully synthetic mesoporous geopolymer drug carrier for controlled release of opioids. Nanoparticulate precursor powders with different Al/Si-ratios were synthesized by a sol-gel route and used in the preparation of different geopolymers, which could be structurally tailored by adjusting the Al/Si-ratio and the curing temperatures. In particular, it was shown that the pore sizes of the geopolymers decreased with increasing Al/Si ratio and that completely mesoporous geopolymers could be produced from precursor particles with the Al/Si ratio 2:1. The mesoporosity was shown to be associated with a sustained and linear in vitro release profile of the opioid oxycodone. A clinically relevant release period of about 12 h was obtained by adjusting the size of the pellets. The easily fabricated and tunable geopolymers presented in this study constitute a novel approach in the development of controlled release formulations, not only for opioids, but whenever the clinical indication is best treated with a constant supply of drugs and when the mechanical stability of the delivery vehicle is crucial.

  14. Therapeutic effect of an injectable sustained-release sinomenine hydrochloride and sodium hyaluronate compound in a rabbit model of osteoarthritis.

    Science.gov (United States)

    Liu, Wen-Guang; Ling, Pei-Xue; Lin, Xiu-Kun; Chen, Jian-Ying; Wang, Shao-Jin; Li, Peng; Wu, Xiao-Juan; Zhao, Dong-Mei; Liu, Sheng-Hou

    2012-07-01

    While intra-articular injection of sinomenine hydrochloride has a therapeutic effect on osteoarthritis, it has a short half-life, and is thermolabile and photolabile. The aim of this research was to evaluate the sustained-release of sinomenine hydrochloride from an injectable sinomenine hydrochloride and sodium hyaluronate compound (CSSSI) and its therapeutic effect in a rabbit model of osteoarthritis following intra-articular injection. An injectable compound consisting of 1% sodium hyaluronate and 2.5% sinomenine hydrochloride was prepared and kept as the experiment group, and 2.5% sinomenine hydrochloride was prepared and kept as the control group. The cumulative mass release was measured at different time points in each group in vitro. Sixty-five male Zelanian rabbits were randomly divided into five groups: 15 (30 knees) each for the control, sodium hyaluronate, sinomenine hydrochloride, and CSSSI groups respectively, and five (10 knees) for the modeling group. Papain was injected into both knees of each rabbit for model establishment. Subsequently, 0.2 ml of the corresponding drugs was injected into the articular cavities of the remaining experiment groups, while the control group was treated with 0.2 ml normal saline. All groups were treated once a week for 4 weeks. Seven days after the last treatment, knees were anatomized to perform pathological observations and Mankin's evaluation of the synovium. Four groups were compared using the SPSS 13.0 software package. In the in vitro sustained-release experiments, 90% of the drug was released in the experiment group 360 minutes following the injection. Comparison of the Mankin's evaluations of the four groups illustrated statistical discrepancies (P hyaluronate/sinomenine hydrochloride groups, statistical significance was uniformly obtained. Moreover, sodium hyaluronate and sinomenine hydrochloride treatments showed significant improvement over the modeling control (P hyaluronate vs. sinomenine hydrochloride

  15. Carboxylic acid functionalization of halloysite nanotubes for sustained release of diphenhydramine hydrochloride

    Science.gov (United States)

    Zargarian, S. Sh.; Haddadi-Asl, V.; Hematpour, H.

    2015-05-01

    Halloysite nanotubes (HNT) (cylindrical shape with external diameter and length in the range of 30-80 nm and 0.2-1 µm, respectively) were functionalized with 3-aminopropyltriethoxysilane (APTES) from hydroxyl groups by a coupling reaction. Subsequently, maleic anhydride was attached to the APTES moieties to yield carboxylic acid-functionalized HNT. Loading and subsequent release of a model drug molecule diphenhydramine hydrochloride (DPH) on modified and unmodified nanotubes were investigated. Morphology of HNT was studied by electron microscopy. Successful attachment of APTES and carboxylic acid groups to halloysite and drug loading were evaluated by Fourier transform infrared spectroscopy. The amount of surface modification and drug adsorption capacity were calculated via thermogravimetric analysis. The ordered crystal structure of loaded drug was evaluated by X-ray diffraction. UV-Visible spectrophotometer was used to study drug release from modified and unmodified samples. Carboxylated halloysite exhibits higher loading capacity and prolonged release of DPH as compared to that of the natural halloysite.

  16. Development of a Sustained-Release Voriconazole-Containing Thermogel for Subconjunctival Injection in Horses.

    Science.gov (United States)

    Cuming, Rosemary S; Abarca, Eva M; Duran, Sue; Wooldridge, Anne A; Stewart, Allison J; Ravis, William; Babu, R Jayachandra; Lin, Yuh-Jing; Hathcock, Terri

    2017-05-01

    To determine in vitro release profiles, transcorneal permeation, and ocular injection characteristics of a voriconazole-containing thermogel suitable for injection into the subconjunctival space (SCS). In vitro release rate of voriconazole (0.3% and 1.5%) from poly (DL-lactide-co-glycolide-b-ethylene glycol-b-DL-lactide-co-glycolide) (PLGA-PEG-PLGA) thermogel was determined for 28 days. A Franz cell diffusion chamber was used to evaluate equine transcorneal and transscleral permeation of voriconazole (1.5% topical solution, 0.3% and 1.5% voriconazole-thermogel) for 24 hours. Antifungal activity of voriconazole released from the 1.5% voriconazole-thermogel was determined via the agar disk diffusion method. Ex vivo equine eyes were injected with liquid voriconazole-thermogel (4°C). Distension of the SCS was assessed ultrasonographically and macroscopically. SCS voriconazole-thermogel injections were performed in a horse 1 week and 2 hours before euthanasia and histopathologic analysis of ocular tissues performed. Voriconazole was released from the PLGA-PEG-PLGA thermogel for more than 21 days in all groups. Release followed first-order kinetics. Voriconazole diffused through the cornea and sclera in all groups. Permeation was greater through the sclerae than corneas. Voriconazole released from the 1.5% voriconazole-thermogel showed antifungal activity in vitro. Voriconazole-thermogel was easily able to be injected into the dorsal SCS where it formed a discrete gel deposit. Voriconazole-thermogel was easily injected in vivo and did not induce any adverse reactions. Voriconazole-containing thermogels have potential application in treatment of keratomycosis. Further research is required to evaluate their performance in vivo.

  17. Sustainability assessment of electrokinetic bioremediation compared with alternative remediation options for a petroleum release site.

    Science.gov (United States)

    Gill, R T; Thornton, S F; Harbottle, M J; Smith, J W N

    2016-12-15

    Sustainable management practices can be applied to the remediation of contaminated land to maximise the economic, environmental and social benefits of the process. The Sustainable Remediation Forum UK (SuRF-UK) have developed a framework to support the implementation of sustainable practices within contaminated land management and decision making. This study applies the framework, including qualitative (Tier 1) and semi-quantitative (Tier 2) sustainability assessments, to a complex site where the principal contaminant source is unleaded gasoline, giving rise to a dissolved phase BTEX and MTBE plume. The pathway is groundwater migration through a chalk aquifer and the receptor is a water supply borehole. A hydraulic containment system (HCS) has been installed to manage the MTBE plume migration. The options considered to remediate the MTBE source include monitored natural attenuation (MNA), air sparging/soil vapour extraction (AS/SVE), pump and treat (PT) and electrokinetic-enhanced bioremediation (EK-BIO). A sustainability indictor set from the SuRF-UK framework, including priority indicator categories selected during a stakeholder engagement workshop, was used to frame the assessments. At Tier 1 the options are ranked based on qualitative supporting information, whereas in Tier 2 a multi-criteria analysis is applied. Furthermore, the multi-criteria analysis was refined for scenarios where photovoltaics (PVs) are included and amendments are excluded from the EK-BIO option. Overall, the analysis identified AS/SVE and EK-BIO as more sustainable remediation options at this site than either PT or MNA. The wider implications of this study include: (1) an appraisal of the management decision from each Tier of the assessment with the aim to highlight areas for time and cost savings for similar assessments in the future; (2) the observation that EK-BIO performed well against key indicator categories compared to the other intensive treatments; and (3) introducing methods to

  18. The Sustainable Release of Vancomycin and Its Degradation Products From Nanostructured Collagen/Hydroxyapatite Composite Layers

    Czech Academy of Sciences Publication Activity Database

    Suchý, Tomáš; Šupová, Monika; Klapková, E.; Horný, L.; Rýglová, Šárka; Žaloudková, Margit; Braun, Martin; Sucharda, Zbyněk; Ballay, R.; Veselý, J.; Chlup, H.; Denk, František

    2016-01-01

    Roč. 105, č. 3 (2016), 1288-1294 ISSN 0022-3549 R&D Projects: GA TA ČR(CZ) TA04010330 Institutional support: RVO:67985891 Keywords : anti-infectives * HPLC * coating * controlled release * degradation products * drug delivery systems * nanoparticles * pharmacokinetics * polymeric drug delivery systems Subject RIV: JI - Composite Materials Impact factor: 2.713, year: 2016

  19. Selection of 12-Hour Sustained-Release Acetaminophen (Paracetamol) Formulation Through Comparison of Pharmacokinetic Profiles of 4 Sustained-Release Prototype Formulations and Standard Acetaminophen Formulation: An Open-Label, Randomized, Proof-of-Principle Pharmacokinetic Study.

    Science.gov (United States)

    Yue, Yong; Liu, Dongzhou J

    2017-08-16

    Acetaminophen (APAP; paracetamol), a widely used analgesic and antipyretic, is available in modified-release and immediate-release (IR) formulations requiring 3- or 4-times-daily dosing. This phase 1 open-label crossover study compared pharmacokinetic profiles of single 2000-mg doses of 4 different sustained-release (SR) formulations of APAP (designed to allow twice-daily dosing) against two 1000-mg doses (taken 6 hours apart) of standard IR APAP in 14 healthy volunteers. The primary end point was duration of time that plasma APAP concentration exceeded a plasma concentration (TC ) of 4 μg/mL. Of the 4 SR APAP formulations studied, a single 2000-mg dose of a bilayer SR formulation had the longest mean TC>4μg/mL (8.1 hours), similar to that of 2 doses of IR APAP (8.3 hours). Mean TC>4μg/mL was 7.3 hours with a single-layer SR APAP, 7.5 hours with another single-layer SR APAP formulation using a different excipient, and 7.1 hours with an enteric-coated SR APAP coupled with a fast-dissolving IR APAP. Secondary pharmacokinetic analyses showed a similar extent of absorption and lower peak concentration for the bilayer SR formulation compared with IR APAP. Adverse events were all mild. Based on these results, the bilayer SR APAP formulation was selected for further development. © 2017, The American College of Clinical Pharmacology.

  20. A Meta-Analysis of the Efficacy of Bupropion Sustained-Release for Smoking Cessation in Heavy Smokers

    Directory of Open Access Journals (Sweden)

    Adrian Paszek

    2017-09-01

    Full Text Available Cigarette smoking damages just about every organ in the body and reduces overall health. Even with the prevalence of accessible nicotine replacement therapies and behavioral counseling, there remains a need for alternative therapies to improve the odds of successfully abstaining from smoking in the long term. Bupropion sustained-release (SR is a pharmacological, prescription-only intervention that is approved as a first-line treatment for smoking cessation. This meta-analysis examines the effectiveness of bupropion sustained-release for smoking cessation amongst heavy smokers, defined as those who consistently smoke at least fifteen or more cigarettes per day. Across five qualifying studies, bupropion SR increased odds of cessation over placebo treatment at six and twelve months. Bupropion SR is a well-tolerated, non-nicotinic therapy for smoking cessation. Treatment with bupropion SR reduces initial cravings and withdrawal effects but does not appear to address the multi-faceted problem of cigarette addiction, resulting in decreased abstinence rates over time. An integrated approach incorporating bupropion SR with other interventions, such as nicotine replacement therapies and psychotherapy, may provide the necessary means to achieve lasting cessation and promote well-being.

  1. Development and Validation of a RP-HPLC Method for Determination of Nimodipine in Sustained Release Tablets

    Directory of Open Access Journals (Sweden)

    Xiaojun Shang

    2013-01-01

    Full Text Available A rapid, sensitive, and reproducible reverse phase high performance liquid chromatographic (RP-HPLC method with UV detector for the determination of nimodipine in sustained release tablets was developed. The method involved using a SinoChoom ODS-BP C18 reversed phase column (5 μm, 4.6 mm × 200 mm and mobile phase consisting of methanol-acetonitrile-water (35 : 38 : 27, v/v. The flow rate is 1.0 mL/min, the UV detector was operated at 237 nm, and the column was maintained at 25°C. The method was validated according to official compendia guidelines. The calibration curve of nimodipine for RP-HPLC method was linear over the range of 10–100 μg/mL. The retention time was found at 7.50 min for nimodipine. The variation for interday and intraday assay was found to be less than 0.72%. The proposed RP-HPLC was proved to be suitable for the determination of nimodipine in sustained release tablets.

  2. Sustained-release study on Exenatide loaded into mesoporous silica nanoparticles: in vitro characterization and in vivo evaluation.

    Science.gov (United States)

    Chen, Cuiwei; Zheng, Hongyue; Xu, Junjun; Shi, Xiaowei; Li, Fanzhu; Wang, Xuanshen

    2017-09-04

    Exenatide (EXT), the first glucagon-like peptide-1 receptor agonist, has been approved as an adjunctive therapy for patients with type 2 diabetes. Due to EXT's short half-life, EXT must be administrated by continuous subcutaneous (s.c.) injection twice daily. In previous studies, many studies on EXT loaded into polymer materials carriers for sustained release had been reported. However, these carriers have some defects, such as hydrophobicity, low surface energy, low mechanical strength, and poor chemical stability. Therefore, this study aims to develop a novel drug delivery system, which is EXT loaded into well-ordered hexagonal mesoporous silica structures (EXT-SBA-15), to control the sustainability of EXT. SBA-15 was prepared by hydrothermal method with uniform size. Morphology of SBA-15 was employed by transmission electron microscopy. The pore size of SBA-15 was characterized by N2 adsorption-desorption isotherms. The in vitro drug release behavior and pharmacokinetics of EXT-SBA-15 were investigated. Furthermore, the blood glucose levels of diabetic mice were monitored after subcutaneous injection of EXT-Sol and EXT-SBA-15 to evaluate further the stable hypoglycemic effect of EXT-SBA-15. EXT-SBA-15 showed a higher drug loading efficiency (15.2 ± 2.0%) and sustained-release features in vitro. In addition, pharmacokinetic studies revealed that the EXT-SBA-15 treatment group extended the half-life t 1/2(β) to 14.53 ± 0.70 h compared with that of the EXT solution (EXT-Sol) treatment group (0.60 ± 0.08 h) in vivo. Results of the pharmacodynamics study show that the EXT-SBA-15 treatment group had inhibited blood glucose levels below 20 mmol/L for 25 days, and the lowest blood glucose level was 13 mmol/L on the 10th day. This study demonstrates that the EXT-SBA-15 delivery system can control the sustainability of EXT and contribute to improve EXT clinical use.

  3. Stimulation of Rotator Cuff Repair by Sustained Release of Bone Morphogenetic Protein-7 Using a Gelatin Hydrogel Sheet.

    Science.gov (United States)

    Kabuto, Yukichi; Morihara, Toru; Sukenari, Tsuyoshi; Kida, Yoshikazu; Oda, Ryo; Arai, Yuji; Sawada, Koshiro; Matsuda, Ken-Ichi; Kawata, Mitsuhiro; Tabata, Yasuhiko; Fujiwara, Hiroyoshi; Kubo, Toshikazu

    2015-07-01

    Bone morphogenetic protein-7 (BMP-7) promotes not only osteogenesis but also matrix production in chondrocytes and tenocytes. However, because of its short half-life, maintaining local concentrations of BMP-7 is difficult. We examined the use of a gelatin hydrogel sheet (GHS) for the sustained release of BMP-7 in stimulating rotator cuff repair at the tendon-to-bone insertion. Twelve-week-old male Sprague-Dawley rats were used. Radiolabeled BMP-7 ((125)I-BMP-7) was injected into the subacromial bursa in the (125)I-BMP-7 group, whereas a GHS impregnated with (125)I-BMP-7 was implanted on the tendon attached to the tendon-to-bone insertion in the (125)I-BMP-7+GHS group. Levels of (125)I-BMP-7 in the tendon-to-bone insertion were assessed at 1, 3, 7, 14, and 21 postoperative days. The BMP-7 concentrations were significantly higher in the (125)I-BMP-7+GHS group than in the (125)I-BMP-7 group. Next, the bilateral supraspinatus tendons were resected and sutured to the greater tuberosity of the humerus using the Mason-Allen technique. Treatment groups were created as follows: either phosphate-buffered saline (PBS) or BMP-7 was injected into the subacromial bursa in the PBS and BMP-7 groups, whereas a GHS impregnated with either PBS or BMP-7 was implanted on the repaired tendon attached to the tendon-to-bone insertion in the PBS+GHS and BMP-7+GHS groups. The resected specimens were stained at 2, 4, and 8 postoperative weeks with hematoxylin and eosin as well as Safranin O, and tissue repair was evaluated histologically by using the tendon-to-bone maturing score. Tissue repair was assessed biomechanically at 4 and 8 postoperative weeks. The BMP-7+GHS group at 8 postoperative weeks demonstrated a favorable cartilage matrix production and tendon orientation; moreover, the tendon-to-bone maturing score and the ultimate force-to-failure were the highest in this group. The ability of GHS to provide controlled release of various growth factors has been previously reported. We

  4. Fully embeddable chitosan microneedles as a sustained release depot for intradermal vaccination.

    Science.gov (United States)

    Chen, Mei-Chin; Huang, Shih-Fang; Lai, Kuan-Ying; Ling, Ming-Hung

    2013-04-01

    This study introduces a microneedle transdermal delivery system, composed of embeddable chitosan microneedles and a poly(L-lactide-co-D,L-lactide) (PLA) supporting array, for complete and sustained delivery of encapsulated antigens to the skin. Chitosan microneedles were mounted to the top of a strong PLA supporting array, providing mechanical strength to fully insert the microneedles into the skin. When inserted into rat skin in vivo, chitosan microneedles successfully separated from the supporting array and were left within the skin for sustained drug delivery without requiring a transdermal patch. The microneedle penetration depth was approximately 600 μm (i.e. the total length of the microneedle), which is beneficial for targeted delivery of antigens to antigen-presenting cells in the epidermis and dermis. To evaluate the utility of chitosan microneedles for intradermal vaccination, ovalbumin (OVA; MW = 44.3 kDa) was used as a model antigen. When the OVA-loaded microneedles were embedded in rat skin in vivo, histological examination showed that the microneedles gradually degraded and prolonged OVA exposure at the insertion sites for up to 14 days. Compared to traditional intramuscular immunization, rats immunized by a single microneedle dose of OVA showed a significantly higher OVA-specific antibody response which lasted for at least 6 weeks. These results suggest that embeddable chitosan microneedles are a promising depot for extended delivery of encapsulated antigens to provide sustained immune stimulation and improve immunogenicity. Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. Effect of functionalization of polymeric nanoparticles incorporated with whole attenuated rabies virus antigen on sustained release and efficacy

    Directory of Open Access Journals (Sweden)

    Kiran Nivedh

    2016-12-01

    Full Text Available Nanovaccines introduced a new dimension to prevent or cure diseases in an efficient and sustained manner. Various polymers have been used for the drug delivery to increase the therapeutic value with minimal side effects. Thus the present study incorporates both nanotechnology and polymers for the drug delivery. Poly(d,l-lactic-co-glycolic acid-b-poly(ethylene glycol was incorporated with the rabies whole attenuated viral antigen using double emulsion (W/O/W method and characterized by Scanning Electron Microscopy (SEM and Atomic Force Microscopy (AFM. Chitosan-PEG nanoparticles incorporated with the rabies whole attenuated virus antigen (CS-PEG NP-RV Ag. were prepared using Ionic Gelation method. The CS-PEG NP-RV Ag. was surface modified with biocompatible polymers such as Acacia, Bovine Serum Albumin (BSA, Casein, Ovalbumin and Starch by Ionic Gelation method. The morphology was confirmed by SEM and Transmission Electron Microscopy (TEM. The surface modification was confirmed by Fourier Transform Infrared Spectroscopy (FTIR, Zeta potential. The size distribution of CS-PEG-RV Ag. and surface modified CS-PEG-RV Ag. by respective biocompatible polymers was assessed by Zetasizer. Release profile of both stabilized nanoparticles was carried out by modified centrifugal ultrafiltration method which showed the sustained release pattern of the Rabies Ag. Immune stimulation under in-vitro condition was studied using rosette assay and phagocytosis assay. In-vitro toxicity using human blood and genotoxicity using human blood DNA was also studied to assess the toxicity of the nanoformulations. The results of these studies infer that PLGA-b-PEG nanoparticles, CS-PEG and surface modified CS-PEG nanoparticles may be an efficient nanocarrier for the RV Ag. to elicit immune response sustainably with negligible toxic effect to the human system.

  6. Alginate hydrogels allow for bioactive and sustained release of VEGF-C and VEGF-D for lymphangiogenic therapeutic applications.

    Science.gov (United States)

    Campbell, Kevin T; Hadley, Dustin J; Kukis, David L; Silva, Eduardo A

    2017-01-01

    Lymphatic dysfunction is associated with the progression of many cardiovascular disorders due to their role in maintaining tissue fluid homeostasis. Promoting new lymphatic vessels (lymphangiogenesis) is a promising strategy to reverse these cardiovascular disorders via restoring lymphatic function. Vascular endothelial growth factor (VEGF) members VEGF-C and VEGF-D are both potent candidates for stimulating lymphangiogenesis, though maintaining spatial and temporal control of these factors represents a challenge to developing efficient therapeutic lymphangiogenic applications. Injectable alginate hydrogels have been useful for the controlled delivery of many angiogenic factors, including VEGF-A, to stimulate new blood vasculature. However, the utility of these tunable hydrogels for delivering lymphangiogenic factors has never been closely examined. Thus, the objective of this study was to utilize ionically cross-linked alginate hydrogels to deliver VEGF-C and VEGF-D for potential lymphangiogenic applications. We demonstrated that lymphatic endothelial cells (LECs) are sensitive to temporal presentation of VEGF-C and VEGF-D but with different responses between the factors. The greatest LEC mitogenic and sprouting response was observed for constant concentrations of VEGF-C and a high initial concentration that gradually decreased over time for VEGF-D. Additionally, alginate hydrogels provided sustained release of radiolabeled VEGF-C and VEGF-D. Finally, VEGF-C and VEGF-D released from these hydrogels promoted a similar number of LEC sprouts as exogenously added growth factors and new vasculature in vivo via a chick chorioallantoic membrane (CAM) assay. Overall, these findings demonstrate that alginate hydrogels can provide sustained and bioactive release of VEGF-C and VEGF-D which could have applications for therapeutic lymphangiogenesis.

  7. Hydroxyapatite-alginate nanocomposite as drug delivery matrix for sustained release of ciprofloxacin.

    Science.gov (United States)

    Venkatasubbu, G Devanand; Ramasamy, S; Ramakrishnan, V; Kumar, J

    2011-12-01

    Hydroxyapatite is a bioceramic which has a wide range of medical application for bone diseases. To enhance its usage, we have prepared ciprofloxacin loaded nano hydroxyapatite (HA) composite with a natural polymer, alginate, using wet chemical method at low temperature. The prepared composites were analyzed by various physicochemical methods. The results show that the nano HA crystallites are well intact with the alginate macromolecules. For the composite system FT-IR and micro Raman results are reported in this paper. Studies on the drug loading and drug release have been done. The drug is pre-adsorbed onto the ceramic particle before the formation of composite. The thermal behavior of composite has been studied using thermo gravimetric analysis (TGA). This work, reports that the nanocomposite prepared under optimum condition could prolong the release of ciprofloxacin compared with the ciprofloxacin loaded hydroxyapatite.

  8. Development of Water-Triggered Chitosan Film Containing Glucamylase for Sustained Release of Resveratrol.

    Science.gov (United States)

    Zhang, Dongliang; Cao, Yanfei; Ma, Chengye; Chen, Shanfeng; Li, Hongjun

    2017-03-29

    There is a paradox when incorporating enzyme into an edible chitosan film that chitosan is dissolved in acid solution and enzyme activity is maintained under mild conditions. A method for maintaining the pH of the chitosan solution at 4-6 to prepare a chitosan film containing β-cyclodextrin, resveratrol-β-cyclodextrin inclusion (RCI), was developed, using glucamylase and acetic acid. A considerable amount of resveratrol was released by the glucamylase-incorporated film within 15 days, and the maximum amount released was 46% of the total resveratrol content. The highest resveratrol release ratio (released resveratrol/total resveratrol) was obtained in the film with 6 mL of RCI. Scratches and spores were generated on the surface of the glucamylase-added film immersed in water (GAFW) for 7 days because of β-cyclodextrin hydrolysis during film drying and water immersion. RCI and β-cyclodextrin were extruded from the film surface and formed teardrops, which were erased by water on the GAFW surface but appeared on the glucamylase-added film without water immersion (GAF). The bubbles generated by the reaction of acetic acid and residual sodium bicarbonate were observed in both glucamylase-free films immersed in water (GFFW) for 7 days and without water immersion (GFF). The FT-IR spectra illustrated that the covalent bond was not generated during water immersion and β-cyclodextrin hydrolysis. The crystal structure of chitosan was destroyed by water immersion and β-cyclodextrin hydrolysis, resulting in the lowest chitosan crystallization peak at 22°. The increasing of water holding capacity determined by EDX presented the following order: GAF, GFFW, GFF, and GAFW.

  9. Preparation and characterization of silk fibroin hydrogel as injectable implants for sustained release of Risperidone.

    Science.gov (United States)

    Ebrahimi, Atefeh; Sadrjavadi, Komail; Hajialyani, Marziyeh; Shokoohinia, Yalda; Fattahi, Ali

    2018-02-01

    The principal objective of the present study is to achieve a depot formulation of Risperidone by gelation of silk fibroin (SF). For this purpose, hydrochloric acid (HCl)/acetone-based and methanol-based hydrogels were prepared with different drug/polymer ratios (1:3, 1:6, and 1:15). For all the drug-loaded methanol-based hydrogels, gel transition of SF solutions occurred immediately and the gelation time was 1 min, while the gelation time of HCL/acetone-based hydrogels was around 360 min. According to the results obtined from Fourier transform infrared spectroscopy (FT-IR) and X-ray diffraction (XRD) spectra, solvent systems and Risperidone could induce β-sheet structure, but HCL/acetone system had the lowest effect on induction of β-sheets. The crystallinity was increased by increasing the amount of Risperidone, and drug to polymer ratio of 1:3 possessed the highest crystallinity. Thermogravimetric analysis (TGA) indicated that increasing the amount of drug in formulation increased the stability of hydrogels, and methanol-based hydrogel with a ratio of 1:3 had the most stable structure. The release rate of Risperidone from methanol-based hydrogel at ratio of 1:3 was lower than that for HCl/acetone-based one, and it decreased by increasing the amount of Risperidone. The release of Risperidone from methanol hydrogel at ratios 1:3 and 1:6 continued up to 25 d which is acceptable for depot form of Risperidone and shows that the extended release of Risperidone was achieved successfully. In conclusion, SF hydrogel with the ability to respond to the environmental stimuli is an excellent candidate for injectable implants for extended release of Risperidone.

  10. Carboxylic acid functionalization of halloysite nanotubes for sustained release of diphenhydramine hydrochloride

    Energy Technology Data Exchange (ETDEWEB)

    Zargarian, S. Sh.; Haddadi-Asl, V., E-mail: haddadi@aut.ac.ir; Hematpour, H. [Amirkabir University of Technology, Department of Polymer Engineering and Color Technology (Iran, Islamic Republic of)

    2015-05-15

    Halloysite nanotubes (HNT) (cylindrical shape with external diameter and length in the range of 30–80 nm and 0.2–1 µm, respectively) were functionalized with 3-aminopropyltriethoxysilane (APTES) from hydroxyl groups by a coupling reaction. Subsequently, maleic anhydride was attached to the APTES moieties to yield carboxylic acid-functionalized HNT. Loading and subsequent release of a model drug molecule diphenhydramine hydrochloride (DPH) on modified and unmodified nanotubes were investigated. Morphology of HNT was studied by electron microscopy. Successful attachment of APTES and carboxylic acid groups to halloysite and drug loading were evaluated by Fourier transform infrared spectroscopy. The amount of surface modification and drug adsorption capacity were calculated via thermogravimetric analysis. The ordered crystal structure of loaded drug was evaluated by X-ray diffraction. UV–Visible spectrophotometer was used to study drug release from modified and unmodified samples. Carboxylated halloysite exhibits higher loading capacity and prolonged release of DPH as compared to that of the natural halloysite.

  11. Development and in vitro characterization of floating sustained-release drug delivery systems of polyphenols.

    Science.gov (United States)

    Rosenzweig, Ohad; Lavy, Eran; Gati, Irith; Kohen, Ron; Friedman, Michael

    2013-01-01

    The aim of this study was to develop and characterize floating stomach-retentive matrix tablets that will deliver polyphenols in a controlled release manner. The tablets were prepared by direct compression. A number of polymers were examined and egg albumin was chosen in light of a better performance in terms of floating behavior and decomposition time. Dissolution studies for three representative polyphenols loaded into a number of formulations were performed using the "f₂" factor in order to compare release profiles of different polyphenols and formulations. The release data showed a good fit into the power law equation and zero-order kinetics has been determined for some of the systems. Erosion and textural analysis studies revealed that higher concentration of egg albumin results in a higher gel strength that is less susceptible to erosion, potentially leading to a prolonged delivery time of drug. The ability of egg albumin-based tablets to resist high mechanical forces was also determined, while comparison to cellulose-derived polymers revealed that the latter have a much lower ability to resist the same forces. The developed delivery system has the potential to increase the efficacy of the therapy for various pathological stomach conditions and to improve patient compliance.

  12. Polymeric and Solid Lipid Nanoparticles for Sustained Release of Carbendazim and Tebuconazole in Agricultural Applications

    Science.gov (United States)

    Campos, Estefânia Vangelie Ramos; Oliveira, Jhones Luiz De; da Silva, Camila Morais Gonçalves; Pascoli, Mônica; Pasquoto, Tatiane; Lima, Renata; Abhilash, P. C.; Fernandes Fraceto, Leonardo

    2015-09-01

    Carbendazim (MBC) (methyl-2-benzimidazole carbamate) and tebuconazole (TBZ) ((RS)-1-(4-chlorophenyl)-4,4-dimethyl-3-(1H-1,2,4-triazol-1-ylmethyl)pentan-3-ol) are widely used in agriculture for the prevention and control of fungal diseases. Solid lipid nanoparticles and polymeric nanocapsules are carrier systems that offer advantages including changes in the release profiles of bioactive compounds and their transfer to the site of action, reduced losses due to leaching or degradation, and decreased toxicity in the environment and humans. The objective of this study was to prepare these two types of nanoparticle as carrier systems for a combination of TBZ and MBC, and then investigate the release profiles of the fungicides as well as the stabilities and cytotoxicities of the formulations. Both nanoparticle systems presented high association efficiency (>99%), indicating good interaction between the fungicides and the nanoparticles. The release profiles of MBC and TBZ were modified when the compounds were loaded in the nanoparticles, and cytotoxicity assays showed that encapsulation of the fungicides decreased their toxicity. These fungicide systems offer new options for the treatment and prevention of fungal diseases in plants.

  13. Sustained Release and Cytotoxicity Evaluation of Carbon Nanotube-Mediated Drug Delivery System for Betulinic Acid

    Directory of Open Access Journals (Sweden)

    Julia M. Tan

    2014-01-01

    Full Text Available Carbon nanotubes (CNTs have been widely utilized as a novel drug carrier with promising future applications in biomedical therapies due to their distinct characteristics. In the present work, carboxylic acid-functionalized single-walled carbon nanotubes (f-SWCNTs were used as the starting material to react with anticancer drug, BA to produce f-SWCNTs-BA conjugate via π-π stacking interaction. The conjugate was extensively characterized for drug loading capacity, physicochemical properties, surface morphology, drug releasing characteristics, and cytotoxicity evaluation. The results indicated that the drug loading capacity was determined to be around 20 wt% and this value has been verified by thermogravimetric analysis. The binding of BA onto the surface of f-SWCNTs was confirmed by FTIR and Raman spectroscopies. Powder XRD analysis showed that the structure of the conjugate was unaffected by the loading of BA. The developed conjugate was found to release the drug in a controlled manner with a prolonged release property. According to the preliminary in vitro cytotoxicity studies, the conjugate was not toxic in a standard fibroblast cell line, and anticancer activity was significantly higher in A549 than HepG2 cell line. This study suggests that f-SWCNTs could be developed as an efficient drug carrier to conjugate drugs for pharmaceutical applications in cancer chemotherapies.

  14. Multilayer, degradable coating as a carrier for the sustained release of antibiotics: preparation and antimicrobial efficacy in vitro.

    Science.gov (United States)

    Guillaume, Olivier; Garric, Xavier; Lavigne, Jean-Philippe; Van Den Berghe, Helene; Coudane, Jean

    2012-09-28

    One of the most critical post-surgical complications is mesh-related infection. This paper describes how a commercially available polypropylene (PP) mesh was modified to minimize the risk of post-implantation infection. A dual drug-release coating was created around mesh filaments using an airbrush spray system. This coating was composed of three layers containing ofloxacin and rifampicin dispersed in a degradable polymer reservoir made up of [poly(ε-caprolactone) (PCL) and poly(DL-lactic acid) (PLA)]. Drug release kinetics were managed by varying the structure of the degradable polymer and the multilayer coating. In vitro, this new drug delivery polymer system was seen to be more rapidly invaded by fibroblasts than was the initial PP mesh. Active mesh showed excellent antibacterial properties with regard to microorganism adhesion, biofilm formation and the periprosthetic inhibition of bacterial growth. Sustained release of the two antibiotics from the coated mesh prevented mesh contamination for at least 72 h. This triple-layer coating technology is potentially of great interest for it can be easily extrapolated to other medical devices and drug combinations for the prevention or treatment of other diseases. Copyright © 2012 Elsevier B.V. All rights reserved.

  15. Sustained-release effervescent floating matrix tablets of baclofen: development, optimization and in vitro-in vivo evaluation in healthy human volunteers.

    Science.gov (United States)

    Gande, S; Rao, Ym

    2011-01-01

    Baclofen, a centrally acting skeletal muscle relaxant, is indicated in the long-term treatment of spasticity. It is difficult to formulate baclofen sustained release dosage forms because its absorption on arrival to colon (or even before) is low or nonexistent. In the present investigation efforts were made to improve the bioavailability of baclofen by increasing the residence time of the drug through sustained-release matrix tablet formulation via gastroretentive mechanism. Tablets were prepared by wet granulation technique. The influence of gas generating and gel forming agents, amount of baclofen and total weight of tablet on physical properties, in vitro buoyancy, floating lag time, drug release, DSC, X-ray studies were investigated. The release mechanisms were explored and explained by applying zero order, first order, Higuchi and Korsmeyer equations. The selected formulations were subjected to stability study for the period of three months. For all formulations, kinetics of drug release from tablet followed Higuchi's square root of time kinetic treatment heralding diffusion as predominant mechanism of drug release. Formulations containing 20 mg and 40 mg (F-1 and F-7) showed similar release profiles. There was no significant change in the selected formulations, when subjected to accelerated stability conditions over a period of three months. X-ray imaging in six healthy human volunteers revealed a mean gastric retention period of 5.50±0.7 hrs for the selected formulation. Stable, sustained release effervescent floating matrix tablets of baclofen could be prepared by wet granulation technique.

  16. A diels-alder modulated approach to control and sustain the release of dexamethasone and induce osteogenic differentiation of human mesenchymal stem cells

    Science.gov (United States)

    Koehler, Kenneth C.; Alge, Daniel L.; Anseth, Kristi S.; Bowman, Christopher N.

    2013-01-01

    We report a new approach to controlled drug release based upon exploiting the dynamic equilibrium that exists between Diels-Alder reactants and products, demonstrating the release of a furan containing dexamethasone peptide (dex-KGPQG-furan) from a maleimide containing hydrogel. Using a reaction-diffusion model, the release kinetics were tuned to achieve sustained concentrations conducive to osteogenic differentiation of human mesenchymal stem cells (hMSCs). Efficacy was first demonstrated in a 2D culture model, in which dexamethasone release induced significant increases in alkaline phosphatase (ALP) activity and mineral deposition in hMSCs compared to a dexamethasone-free treatment. The results were similar to that observed with a soluble dexamethasone treatment. More dramatic differences were observed in 3D culture, where co-encapsulation of a dexamethasone releasing hydrogel depot within an hMSC-laden extracellular matrix mimetic poly(ethylene glycol) hydrogel resulted in a local and robust osteogenic differentiation. ALP activity reached levels that were up to six times higher than the dexamethasone free treatment. Interestingly, at 5 and 10 day time points, the ALP activity exceeded the dexamethasone positive control, suggesting a potential benefit of sustained release in 3D culture. After 21 days, substantial mineralization comparable to the positive control was also observed in the hydrogels. Collectively, these results demonstrate Diels-Alder modulated release as an effective and versatile new platform for controlled drug delivery that may prove especially beneficial for sustaining the release of low molecular weight molecules in hydrogel systems. PMID:23465826

  17. Modification of concomitant drug release from oil vehicles using drug-prodrug combinations to achieve sustained balanced analgesia after joint installation

    DEFF Research Database (Denmark)

    Thing, Mette; Jensen, Sabrine Smedegaard; Larsen, Claus Selch

    2012-01-01

    ,N-diethyl glycolamide ester of naproxen and ropivacaine from an oil vehicle consisting of medium-chain triglycerides were investigated in vitro. The release into both phosphate buffer and 80% (v/v) synovial fluid at pH 7.4 was examined in two dialysis membrane-based release models. The ester prodrug exhibited high...... solubility in medium-chain triglyceride, a high partition coefficient and was rapidly converted to naproxen in synovial fluid. Compared to naproxen, the release of the prodrug from the oil was sustained. In synovial fluid, the reconversion to naproxen resulted in faster release compared to that observed...... using buffer. In both release models, the use of ropivacaine-prodrug combination provided concomitant release from the oil into synovial fluid with ropivacaine being released faster than naproxen. The use of lipophilic prodrugs that are converted fast to the parent drug in synovial fluid seems...

  18. Sustained Na+/H+ exchanger activation promotes gliotransmitter release from reactive hippocampal astrocytes following oxygen-glucose deprivation.

    Directory of Open Access Journals (Sweden)

    Pelin Cengiz

    Full Text Available Hypoxia ischemia (HI-related brain injury is the major cause of long-term morbidity in neonates. One characteristic hallmark of neonatal HI is the development of reactive astrogliosis in the hippocampus. However, the impact of reactive astrogliosis in hippocampal damage after neonatal HI is not fully understood. In the current study, we investigated the role of Na(+/H(+ exchanger isoform 1 (NHE1 protein in mouse reactive hippocampal astrocyte function in an in vitro ischemia model (oxygen/glucose deprivation and reoxygenation, OGD/REOX. 2 h OGD significantly increased NHE1 protein expression and NHE1-mediated H(+ efflux in hippocampal astrocytes. NHE1 activity remained stimulated during 1-5 h REOX and returned to the basal level at 24 h REOX. NHE1 activation in hippocampal astrocytes resulted in intracellular Na(+ and Ca(2+ overload. The latter was mediated by reversal of Na(+/Ca(2+ exchange. Hippocampal astrocytes also exhibited a robust release of gliotransmitters (glutamate and pro-inflammatory cytokines IL-6 and TNFα during 1-24 h REOX. Interestingly, inhibition of NHE1 activity with its potent inhibitor HOE 642 not only reduced Na(+ overload but also gliotransmitter release from hippocampal astrocytes. The noncompetitive excitatory amino acid transporter inhibitor TBOA showed a similar effect on blocking the glutamate release. Taken together, we concluded that NHE1 plays an essential role in maintaining H(+ homeostasis in hippocampal astrocytes. Over-stimulation of NHE1 activity following in vitro ischemia disrupts Na(+ and Ca(2+ homeostasis, which reduces Na(+-dependent glutamate uptake and promotes release of glutamate and cytokines from reactive astrocytes. Therefore, blocking sustained NHE1 activation in reactive astrocytes may provide neuroprotection following HI.

  19. Ciprofloxacin-imprinted hydrogels for drug sustained release in aqueous media.

    Science.gov (United States)

    Kioomars, Sajedeh; Heidari, Somayeh; Malaekeh-Nikouei, Bizhan; Shayani Rad, Maryam; Khameneh, Bahman; Mohajeri, Seyed Ahmad

    2017-02-01

    In this study several ciprofloxacin (CFX) imprinted and non-imprinted hydrogels were prepared and evaluated as ocular drug delivery systems in aqueous media. 2-Hydroxyethyl methacrylate (HEMA) was used as a solvent and backbone monomer, ethylene glycol dimethacrylate (EGDMA) as a cross-linker, methacrylic acid (MAA) as a functional monomer and CFX as the template molecule. CFX-imprinted hydrogels (MIPs) were prepared applying different CFX:MAA molar ratios (1:16, 1:20 and 1:32) in feed composition of monomer solutions. Thermal polymerization was applied and hydrogels were synthesized in a polypropylene mold (0.4 mm thickness). Swelling and binding properties of hydrogels were evaluated in water. Release profile of the MIPs was evaluated in NaCl (0.9%) and artificial tears. The data showed that enhancing the MAA concentration, as a co-monomer, and using molecular imprinting improved binding properties of the synthesized hydrogels. The optimized MIPs with 400 mM MAA and CFX: MAA molar ratio of 1:20 and 1:16 showed the greatest affinity for CFX and the highest ability to control drug release. In vitro antibacterial activity of hydrogels was studied and demonstrated the effect of CFX-loaded hydrogels against Pseudomonas aeruginosa (P. aeruginosa) and Staphylococcus aureus (S. aureus) isolated from patients' eyes. This study indicated antibacterial efficacy of CFX-loaded MIP hydrogels.

  20. Evaluation of sustained release polylactate electron donors for removal of hexavalent chromium from contaminated groundwater

    Energy Technology Data Exchange (ETDEWEB)

    Brodie, E.L.; Joyner, D. C.; Faybishenko, B.; Conrad, M. E.; Rios-Velazquez, C.; Mork, B.; Willet, A.; Koenigsberg, S.; Herman, D.; Firestone, M. K.; Hazen, T. C.; Malave, Josue; Martinez, Ramon

    2011-02-15

    To evaluate the efficacy of bioimmobilization of Cr(VI) in groundwater at the Department of Energy Hanford site, we conducted a series of microcosm experiments using a range of commercial electron donors with varying degrees of lactate polymerization (polylactate). These experiments were conducted using Hanford Formation sediments (coarse sand and gravel) immersed in Hanford groundwater, which were amended with Cr(VI) and several types of lactate-based electron donors (Hydrogen Release Compound, HRC; primer-HRC, pHRC; extended release HRC) and the polylactate-cysteine form (Metal Remediation Compound, MRC). The results showed that polylactate compounds stimulated an increase in bacterial biomass and activity to a greater extent than sodium lactate when applied at equivalent carbon concentrations. At the same time, concentrations of headspace hydrogen and methane increased and correlated with changes in the microbial community structure. Enrichment of Pseudomonas spp. occurred with all lactate additions, and enrichment of sulfate-reducing Desulfosporosinus spp. occurred with almost complete sulfate reduction. The results of these experiments demonstrate that amendment with the pHRC and MRC forms result in effective removal of Cr(VI) from solution most likely by both direct (enzymatic) and indirect (microbially generated reductant) mechanisms.

  1. Coaxial Electrospray of Curcumin-Loaded Microparticles for Sustained Drug Release.

    Directory of Open Access Journals (Sweden)

    Shuai Yuan

    Full Text Available Curcumin exhibits superior anti-inflammatory, antiseptic and analgesic activities without significant side effects. However, clinical dissemination of this natural medicine is limited by its low solubility and poor bio-availability. To overcome this limitation, we propose to encapsulate curcumin in poly(lactic-co-glycolic acid (PLGA microparticles (MPs by an improved coaxial electrospray (CES process. This process is able to generate a stable cone-jet mode in a wide range of operation parameters in order to produce curcumin-loaded PLGA MPs with a clear core-shell structure and a designated size of several micrometers. In order to optimize the process outcome, the effects of primary operation parameters such as the applied electric voltages and the liquid flow rates are studied systemically. In vitro drug release experiments are also carried out for the CES-produced MPs in comparison with those by a single axial electrospray process. Our experimental results show that the CES process can be effectively controlled to encapsulate drugs of low aqueous solubility for high encapsulation efficiency and optimal drug release profiles.

  2. Sustained release of a p38 inhibitor from non-inflammatory microspheres inhibits cardiac dysfunction

    Science.gov (United States)

    Sy, Jay C.; Seshadri, Gokulakrishnan; Yang, Stephen C.; Brown, Milton; Oh, Teresa; Dikalov, Sergey; Murthy, Niren; Davis, Michael E.

    2008-11-01

    Cardiac dysfunction following acute myocardial infarction is a major cause of death in the world and there is a compelling need for new therapeutic strategies. In this report we demonstrate that a direct cardiac injection of drug-loaded microparticles, formulated from the polymer poly(cyclohexane-1,4-diylacetone dimethylene ketal) (PCADK), improves cardiac function following myocardial infarction. Drug-delivery vehicles have great potential to improve the treatment of cardiac dysfunction by sustaining high concentrations of therapeutics within the damaged myocardium. PCADK is unique among currently used polymers in drug delivery in that its hydrolysis generates neutral degradation products. We show here that PCADK causes minimal tissue inflammatory response, thus enabling PCADK for the treatment of inflammatory diseases, such as cardiac dysfunction. PCADK holds great promise for treating myocardial infarction and other inflammatory diseases given its neutral, biocompatible degradation products and its ability to deliver a wide range of therapeutics.

  3. Interlayer-crosslinked micelles prepared from star-shaped copolymers via click chemistry for sustained drug release

    Science.gov (United States)

    Zhang, Xiaojin; Wang, Hongquan; Dai, Yu

    2017-05-01

    To balance the stability and the particle size of polymeric micelles, star-shaped copolymers Hx-yne-N3-PEG containing both alkynyl and azido groups were synthesized from hyperbranched 2,2-bismethylolpropionic acid polyester (H20 with 16 hydroxyl, H30 with 32 hydroxyl, H40 with 64 hydroxyl) to develop interlayer-crosslinked micelles by click chemistry. The results of dynamic light scattering indicate that the crosslinking could enhance the stability of polymeric micelles. The crosslinked micelles are regular nanosized (approximately 20 nm) spheres observed by a transmission electron microscope. The crosslinked micelles have better drug loading capacity and more sustained drug release behavior than the un-crosslinked micelles.

  4. [Outcomes of an Independent Clinical Study to Compare Branded and Generic Formulations of Sustained-Release Oxycodone].

    Science.gov (United States)

    Yamamoto, Mai; Saito, Yoshiko; Onodera, Yurika; Okawa, Masayo; Shimizu, Kei; Yamamoto, Yusuke; Nawa, Takeshi; Aoyama, Yoshifumi

    2017-03-01

    To evaluate the potential for the adoption of a generic formulation of sustained-release oxycodone(Oxycodone SR Capsules), an independent clinical study was planned to accurately evaluate the efficacy and safety during a 9-day period. After a 3-day pretreatment period, the generic formulation was administered to patients with progressive cancer, who had been treated with a branded formulation(OxyContin®Tablets)of the drug for 5 days at the same dose. This was followed by a 1- day observation period. Drug administration to 3 patients with pulmonary cancer achieved the primary(dose, pain level, and adverse drug reactions)and secondary(rescue dose frequency and quality of life)endpoints, as well as safety goals. The merits of adopting a different dosage form were also noted. Independent data collection using an appropriate evaluation method consequently promoted the understanding of generic opioids in the clinical setting.

  5. Controlled trial for smoking cessation in a Navy shipboard population using nicotine patch, sustained-release buproprion, or both.

    Science.gov (United States)

    Swanson, Nancy A; Burroughs, Charles C; Long, Mark A; Lee, Robert W

    2003-10-01

    This study reports an experimental, randomized controlled clinical trial comparing three treatments for smoking cessation: sustained-release bupropion, nicotine patch, and combination nicotine and bupropion, to a counseling-only control group (N = 140), for smoking sailors aboard seven Navy ships. The purpose was to determine the effectiveness of different pharmcotherapies used in smoking cessation programs. Continuous abstinence was defined as the percentage of subjects who did not smoke since the quit date assessed at 6 and 12 months and having an expired carbon monoxide concentration of <10 ppm at educational sessions 2, 3, and 4. Nine subjects dropped out of the study, and 40 subjects were lost to follow-up. Eleven percent (15/140 subjects) had continuous abstinence at 12 months. The abstinence rates at 12 months were 47% in the control group, as compared with 27% in the nicotine patch/bupropion group, 20% in the nicotine patch group, and 7% in the bupropion group.

  6. A comparative study between melt granulation/compression and hot melt extrusion/injection molding for the manufacturing of oral sustained release thermoplastic polyurethane matrices.

    Science.gov (United States)

    Verstraete, G; Mertens, P; Grymonpré, W; Van Bockstal, P J; De Beer, T; Boone, M N; Van Hoorebeke, L; Remon, J P; Vervaet, C

    2016-11-20

    During this project 3 techniques (twin screw melt granulation/compression (TSMG), hot melt extrusion (HME) and injection molding (IM)) were evaluated for the manufacturing of thermoplastic polyurethane (TPU)-based oral sustained release matrices, containing a high dose of the highly soluble metformin hydrochloride. Whereas formulations with a drug load between 0 and 70% (w/w) could be processed via HME/(IM), the drug content of granules prepared via melt granulation could only be varied between 85 and 90% (w/w) as these formulations contained the proper concentration of binder (i.e. TPU) to obtain a good size distribution of the granules. While release from HME matrices and IM tablets could be sustained over 24h, release from the TPU-based TSMG tablets was too fast (complete release within about 6h) linked to their higher drug load and porosity. By mixing hydrophilic and hydrophobic TPUs the in vitro release kinetics of both formulations could be adjusted: a higher content of hydrophobic TPU was correlated with a slower release rate. Although mini-matrices showed faster release kinetics than IM tablets, this observation was successfully countered by changing the hydrophobic/hydrophilic TPU ratio. In vivo experiments via oral administration to dogs confirmed the versatile potential of the TPU platform as intermediate-strong and low-intermediate sustained characteristics were obtained for the IM tablets and HME mini-matrices, respectively. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Method-of-use study of naltrexone sustained release (SR)/bupropion SR on body weight in individuals with obesity.

    Science.gov (United States)

    Halseth, Amy; Shan, Kevin; Walsh, Brandon; Gilder, Kye; Fujioka, Ken

    2017-02-01

    This study assessed the effects of 32 mg naltrexone sustained release (SR)/360 mg bupropion SR (NB) on body weight in adults with obesity, with comprehensive lifestyle intervention (CLI), for 78 weeks. In this phase 3b, randomized, open-label, controlled study, subjects received NB + CLI or usual care (standard diet/exercise advice) for 26 weeks. NB subjects not achieving 5% weight loss at week 16 were discontinued, as indicated by product labeling. After week 26, usual care subjects began NB + CLI. Assessments continued through week 78. The primary end point was percent change in weight from baseline to week 26 in the per protocol population. Other end points included percentage of subjects achieving ≥5%, ≥10%, and ≥15% weight loss, percent change in weight at week 78, and adverse events (AEs) necessitating study medication discontinuation. NB + CLI subjects lost significantly more weight than usual care subjects at week 26 (8.52% difference; P Weight loss persisted through 78 weeks. In total, 20.7% of subjects discontinued medication for AEs, including 7.0% for nausea. Treatment with NB, used as indicated by prescribing information and with CLI, significantly improved weight loss over usual care alone. NB-facilitated weight loss was sustained for 78 weeks and was deemed safe and well tolerated. © 2016 The Authors. Obesity published by Wiley Periodicals, Inc. onbehalf of The Obesity Society (TOS).

  8. Ion-exchange complex of famotidine: sustained release and taste masking approach of stable liquid dosage form.

    Science.gov (United States)

    Aman, Reham Mokhtar; Meshali, Mahasen Mohamed; Abdelghani, Galal Mahmoud

    2014-12-01

    A stable controlled release resinate-complex for the highly bitter taste famotidine (FAM) was developed to allow once-daily administration and improve patient compliance especially in pediatric and geriatric medicine. The drug-resinate complexes were prepared in different drug to resin (Amberlite IRP-69) ratios by weight (1:1, 1:2, 1:3, 1:4, 1:5 and 1:6). The optimized drug-resinate complex resulted from 1:6 drug to resin ratio experienced maximum drug loading and sustained release property. Hence, it was subjected to physicochemical characterizations by differential scanning colorimetry (DSC), x-ray diffractometry (XRD), Fourier transform infrared spectroscopy (FTIR) and scanning electron microscope (SEM). The optimized complex was further dispensed in the prepared syrup and the suspension was subjected to accelerated stability study, as mentioned in the International Conference on Harmonization (ICH) guidelines. Furthermore, the gustatory properties of the complex were evaluated on humans. The syrup complied successfully with ICH guidelines and sufficiently alleviated the bitterness of famotidine.

  9. Plasma concentrations of buprenorphine following a single subcutaneous administration of a sustained release formulation of buprenorphine in sheep.

    Science.gov (United States)

    Zullian, Chiara; Lema, Pablo; Lavoie, Melissa; Dodelet-Devillers, Aurore; Beaudry, Francis; Vachon, Pascal

    2016-07-01

    The goal of the present study was to evaluate the potential use of slow release buprenorphine in sheep. Twelve adult female sheep (6 Dorset and 6 Suffolk, 12 months of age) were used for this project and were divided into 2 experimental groups (n = 6/group comprising 3 Dorset and 3 Suffolk sheep). Sustained release (SR) buprenorphine was administered subcutaneously in the scapular region at a concentration of 0.1 mg/kg body weight (BW) for group 1 and of 0.05 mg/kg BW for group 2. Following blood collections at selected time points, plasma concentrations of buprenorphine was performed by tandem liquid chromatograph-mass spectrometry. Mean buprenorphine concentration was above 0.1 ng/mL at 48 h up to 192 h post-injection for group 1 and it was above 0.1 ng/mL at 48 h up to 72 h post-injection for group 2. In conclusion, a long lasting potential analgesic plasma level of buprenorphine is attained following a single subcutaneous injection of 0.1 mg/kg BW of SR buprenorphine in sheep. However the effective analgesic plasma threshold still needs to be determined in sheep.

  10. Poly(ε-caprolactone)/triclosan loaded polylactic acid nanoparticles composite: A long-term antibacterial bionanocomposite with sustained release.

    Science.gov (United States)

    Kaffashi, Babak; Davoodi, Saeed; Oliaei, Erfan

    2016-07-11

    In this study, the antibacterial bionanocomposites of poly(ε-caprolactone) (PCL) with different concentrations of triclosan (TC) loaded polylactic acid (PLA) nanoparticles (30wt% triclosan) (LATC30) were fabricated via a melt mixing process in order to lower the burst release of PCL and to extend the antibacterial activity during its performance. Due to the PLA's higher glass transition temperature (Tg) and less flexibility compared with PCL; the PLA nanoparticles efficiently trapped the TC particles, reduced the burst release of TC from the bionanocomposites; and extended the antibacterial property of the samples up to two years. The melt mixing temperature was adjusted to a temperature lower than the melting point of LATC30 nanoparticles; therefore, these nanoparticles were dispersed in the PCL matrix without any chemical reaction and/or drug extraction. The sustained release behavior of TC from PCL remained unchanged since no significant changes occurred in the samples' crystallinity compared with that in the neat PCL. The elastic moduli of samples were enhanced once LATC30 is included. This is necessary since the elastic modulus is decreased with water absorption. The rheological behaviors of samples showed appropriate properties for melt electro-spinning. A stable process was established as the relaxation time of the bionanocomposites was increased. The hydrophilic properties of samples were increased with increasing LATC30. The proliferation rate of the fibroblast (L929) cells was enhanced as the content of nanoparticles was increased. A system similar to this could be implemented to prepare long-term antibacterial and drug delivery systems based on PCL and various low molecular weight drugs. The prepared bionanocomposites are considered as candidates for the soft connective tissue engineering and long-term drug delivery. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Hollow microcapsules built by layer by layer assembly for the encapsulation and sustained release of curcumin.

    Science.gov (United States)

    Manju, S; Sreenivasan, K

    2011-02-01

    Hollow microcapsules fabricated by layer-by-layer assembly (LbL) using oppositely charged polyelectrolytes have figured in studies towards the design of novel drug delivery systems. The possibility of loading a fair amount of active component of poor aqueous solubility is one of the encouraging factors on the wide spread interest of this emerging technology. Curcumin has potent anti-cancer properties. Clinical application of this efficacious agent in cancer and other diseases has been limited due to poor aqueous solubility and consequently minimal systemic bioavailability. LbL constructed polyelectrolyte microcapsules based drug delivery systems have the potential for dispersing hydrophobic agent like curcumin in aqueous media. Here we report the preparation of LbL assembled microcapsules composed of poly(sodium 4-styrene sulfonic acid) and poly(ethylene imine) one after another. The microcapsules were characterized using various analytical techniques. Curcumin was encapsulated in these microcapsules and the efficacy of the released curcumin was studied using L929 cells. Copyright © 2010 Elsevier B.V. All rights reserved.

  12. Novel sustained release and swellable gastroretentive dosage form for ciprofloxacin hydrochloride

    Science.gov (United States)

    Gaikwad, Vinay Dhananjay; Yadav, Vishal Dadasaheb; Gaikwad, Manish Dhananjay

    2014-01-01

    Introduction: The present study aims at developing a gastroretentive swellable and floating matrix tablet formulation of ciprofloxacin hydrochloride (HCl) for the effective treatment of infections caused by susceptible organisms. Ciprofloxacin HCl is a fluoroquinoline antibiotic drug. Ciprofloxacin HCl is more stable in acidic medium and it has a narrow absorption window which is sited at the stomach and proximal portions of the small intestine, so it covers the required criteria for selection of drug for gastroretentive dosage form. Materials and Methods: Ciprofloxacin HCl gastroretentive tablets were formulated by using direct compression method and different grades of hydroxypropyl methylcellulose as suspending and stabilizing agent (polymer), sodium starch glycolate (SSG), crospovidone as disintegrates, sodium bicarbonate as alkalizing agent and magnesium stearate as lubricant. Results: The tablets were evaluated for post compression parameters. All the parameters were within the pharmacopoeial limits. Conclusion: The in vitro dissolution studies showed that the drug release was fast in formulations F2, F4 and F6 containing SSG as super disintegrant when compared with all other formulations. In SEM study of F2 formulation shows maximum swelling and porosity observed after 12 h. Hence, formulation F2 shows the best formulation among the six formulations containing different binders and super disintegrants. PMID:25006553

  13. Intratumoral chemotherapy with a sustained-release drug delivery system inhibits growth of human pancreatic cancer xenografts.

    Science.gov (United States)

    Smith, J P; Stock, E; Orenberg, E K; Yu, N Y; Kanekal, S; Brown, D M

    1995-12-01

    This study provides the first evidence that treatment of human pancreatic adenocarcinoma is markedly improved by the intratumoral administration of chemotherapeutic agents in a novel drug delivery system. The effect of chemotherapeutic agents delivered in a sustained-release, protein-based, injectable gel was evaluated on the growth of human pancreatic adenocarcinoma cell line, BxPC-3. In vitro chemosensitivity of BxPC-3 cells exposed for 24 or 72 h to fluorouracil (0.01-5 mM), cisplatin or doxorubicin (0.1-50 microM) and floxuridine, vinblastine, mitomycin or paclitaxel (1.0-100 microM) was compared with that of untreated cells. In vitro chemosensitivity was also studied with fluorouracil and mitomycin in the poorly differentiated PANC-1, human pancreatic cancer cell line. Survival was determined after 7-10 days. All drugs decreased cell growth in a dose-dependent fashion. The efficacy of fluorouracil, cisplatin and doxorubicin increased with prolonged exposure, rendering these drugs most appropriate for a sustained-release preparation. For in vivo studies, athymic nude mice bearing BxPC-3 xenografts were treated either with fluorouracil, cisplatin or doxorubicin in the therapeutic injectable gel containing epinephrine or with vehicle alone administered intratumorally on days 1 and 4. After 28 days, the mice were sacrificed and tumors dissected and weighed. Tumors in mice treated with the injectable gel decreased in size by 72-79% compared with tumors in untreated controls and tumors treated with vehicle alone. Intratumoral injection of drug solution and intraperitoneal injection of drug in the injectable gel did not change tumor size compared with controls. In a drug-retention study, mice were injected intratumorally with [3H]fluorouracil either in the injectable gel or in solution. Sustained radioactivity was observed in tumors injected with the gel, and, conversely, greater radioactivity was detected in the liver and kidneys in mice receiving the radiolabeled

  14. Development of a Sustainable Release System for a Ranibizumab Biosimilar Using Poly(lactic-co-glycolic acid) Biodegradable Polymer-Based Microparticles as a Platform.

    Science.gov (United States)

    Tanetsugu, Yusuke; Tagami, Tatsuaki; Terukina, Takayuki; Ogawa, Takaya; Ohta, Masato; Ozeki, Tetsuya

    2017-01-01

    Ranibizumab is a humanized monoclonal antibody fragment against vascular endothelial growth factor (VEGF)-A and is widely used to treat age-related macular degeneration (AMD) caused by angiogenesis. Ranibizumab has a short half-life in the eye due to its low molecular weight and susceptibility to proteolysis. Monthly intravitreal injection of a large amount of ranibizumab formulation is a burden for both patients and medical staff. We therefore sought to develop a sustainable release system for treating the eye with ranibizumab using a drug carrier. A ranibizumab biosimilar (RB) was incorporated into microparticles of poly(lactic-co-glycolic acid) (PLGA) biodegradable polymer. Ranibizumab was sustainably released from PLGA microparticles (80+% after 3 weeks). Assay of tube formation by endothelial cells indicated that RB released from PLGA microparticles inhibited VEGF-induced tube formation and this tendency was confirmed by a cell proliferation assay. These results indicate that RB-loaded PLGA microparticles are useful for sustainable RB release and suggest the utility of intraocular sustainable release systems for delivering RB site-specifically to AMD patients.

  15. Long term effects of oral sustained release morphine on neuropsychological performance in patients with chronic non-cancer pain.

    Science.gov (United States)

    Tassain, V; Attal, N; Fletcher, D; Brasseur, L; Dégieux, P; Chauvin, M; Bouhassira, D

    2003-07-01

    Morphine is increasingly used in patients with chronic non-cancer pain, but a major concern associated with chronic use relates to possible cognitive side-effects. The aim of this long-term prospective study was to evaluate the cognitive impact of oral sustained release morphine in patients with non-cancer pain. A battery of neuropsychological tests to explore attention, psychomotor speed and memory was administered. The effects of morphine on pain, quality of life, mood, subjective memory impairment and side-effects were also investigated. Evaluations were performed at baseline in patients free from opioids and then after 3, 6 and 12 months. Twenty-eight patients were included: 18 received oral sustained morphine (range 40-140 mg/day), ten patients stopped morphine prematurely because of side-effects or insufficient pain relief and were followed as a control group. There was no impairment of any neuropsychological variable over time in the morphine treated patients in comparison with the control group. Two measures of information processing speed - the Stroop interference score and the digit symbol test were improved at 6 and 12 months and there were significant correlations with the pain relief and improvement of mood. Self-reported memory impairment improved notably in responders to morphine. Morphine induced persisting effects on pain, and to a lesser extent on quality of life and mood. The visual analog scale score for side-effects increased at 12 months and essentially consisted of gastrointestinal disorders. This study demonstrates that 12 months treatment with oral morphine does not disrupt cognitive functioning in patients with chronic non-cancer pain and instead results in moderate improvement of some aspects of cognitive functioning, as a consequence of the pain relief and concomitant improvement of well-being and mood.

  16. Safety and efficacy of sustained release of basic fibroblast growth factor using gelatin hydrogel in patients with critical limb ischemia.

    Science.gov (United States)

    Kumagai, Motoyuki; Marui, Akira; Tabata, Yasuhiko; Takeda, Takahide; Yamamoto, Masaya; Yonezawa, Atsushi; Tanaka, Shiro; Yanagi, Shigeki; Ito-Ihara, Toshiko; Ikeda, Takafumi; Murayama, Toshinori; Teramukai, Satoshi; Katsura, Toshiya; Matsubara, Kazuo; Kawakami, Koji; Yokode, Masayuki; Shimizu, Akira; Sakata, Ryuzo

    2016-05-01

    As a form of therapeutic angiogenesis, we sought to investigate the safety and efficacy of a sustained-release system of basic fibroblast growth factor (bFGF) using biodegradable gelatin hydrogel in patients with critical limb ischemia (CLI). We conducted a phase I-IIa study that analyzed 10 CLI patients following a 200-μg intramuscular injection of bFGF-incorporated gelatin hydrogel microspheres into the ischemic limb. Primary endpoints were safety and transcutaneous oxygen pressure (TcO2) at 4 and 24 weeks after treatment. During the follow-up, there was no death or serious procedure-related adverse event. After 24 weeks, TcO2 (28.4 ± 8.4 vs. 46.2 ± 13.0 mmHg for pretreatment vs after 24 weeks, p < 0.01) showed significant improvement. Regarding secondary endpoints, the distance walked in 6 min (255 ± 105 vs. 318 ± 127 m, p = 0.02), the Rutherford classification (4.4 ± 0.5 vs. 3.1 ± 1.4, p = 0.02), the rest pain scale (1.7 ± 1.0 vs. 1.2 ± 1.3, p = 0.03), and the cyanotic scale (2.0 ± 1.1 vs. 0.9 ± 0.9, p < 0.01) also showed improvement. The blood levels of bFGF were within the normal range in all patients. A subanalysis of patients with arteriosclerosis obliterans (n = 7) or thromboangiitis obliterans (Buerger's disease) (n = 3) revealed that TcO2 had significantly improved in both subgroups. TcO2 did not differ between patients with or without chronic kidney disease. The sustained release of bFGF from biodegradable gelatin hydrogel may offer a safe and effective form of angiogenesis for patients with CLI.

  17. Parents' views on their children's use of eye drops and willingness to accept a new sustained-release subconjunctival injection

    Directory of Open Access Journals (Sweden)

    Ozdemir S

    2017-10-01

    Full Text Available Semra Ozdemir,1,* Hong King Wu,1,* Eric A Finkelstein,1 Tina T Wong2 1Signature Program in Health Services and Systems Research, Duke-NUS Medical School Singapore, 2Glaucoma Department, Singapore National Eye Centre, Singapore *These authors contributed equally to this work Aim: The objectives of this study were to explore parents' views about their children's use of regular eye drops and whether they would consider a sustained-release subconjunctival injection as a replacement for daily drops.Methods: A survey was conducted with 134 parents of children with chronic eye diseases at the Singapore National Eye Centre. Parents were asked their views about their children’s use of eye drops and were then presented with a discrete choice experiment that, via a series of trade-off tasks, allowed for estimating demand for a series of hypothetical subconjunctival injections that varied along product features, including interval between administrations, risk of complications, out-of-pocket cost and whether it is recommended by the patient’s treating physician.Results: Results showed that the vast majority of parents did not find administration of eye drops to be inconvenient (78% nor did children complain about using daily eye drops (78%. Furthermore, only about half of parents whose child missed doses stated concerns about the consequences of non-compliance. The discrete choice experiment revealed that only one in five parents would consider a subconjunctival injection for their children. These parents tended to be more concerned about the consequences of non-compliance with eye drops, had children who administered the drops themselves or had other chronic disease requiring regular medication. Among these parents, risk of complications had the largest effect on injection uptake.Conclusion: This study shows that parents do not find administration of daily eye drops to be a significant burden. As a result, most would not consider a subconjunctival

  18. Feasibility of localized immunosuppression: 3. Preliminary evaluation of organosilicone constructs designed for sustained drug release in a cell transplant environment using dexamethasone.

    Science.gov (United States)

    Song, Y; Margolles-Clark, E; Fraker, C A; Weaver, J D; Ricordi, C; Pileggi, A; Stabler, C L; Buchwald, P

    2012-05-01

    As part of our ongoing effort to develop biohybrid devices for pancreatic islet transplantation, we are interested in establishing the feasibility of a localized immune-suppressive approach to avoid or minimize the undesirable side effects of existing systemic treatments. Since biohybrid devices can also incorporate biocompatible scaffold constructs to provide a support environment for the transplanted cells that enhances their engraftment and long-term function, we are particularly interested in an approach that would use the same three-dimensional construct, or part of the same construct, to also provide sustained release of therapeutic agents to modulate the inflammatory and immune responses locally. Within this framework, here, we report preliminary results obtained during the investigation of the suitability of organosilicone constructs for providing sustained localized drug release using small, matrix-type polydimethylsiloxane (PDMS) disks and dexamethasone as a model hydrophobic drug. Following a short burst, long-term steady sustained release was observed under in vitro conditions at levels of 0.1-0.5 microg/day/disk with a profile in excellent agreement with that predicted by the Higuchi equation. To verify that therapeutic levels can be achieved, suppression of LPS-induced activation has been shown in THP-1 cells with disks that have been pre-soaked for up to 28 days. These preliminary results prove the feasibility of this approach where an integral part of the biomaterial construct used to enhance cell engraftment and long-term function also serves to provide sustained local drug release.

  19. Improvement of cellular uptake, in vitro antitumor activity and sustained release profile with increased bioavailability from a nanoemulsion platform.

    Science.gov (United States)

    Choudhury, Hira; Gorain, Bapi; Karmakar, Sanmoy; Biswas, Easha; Dey, Goutam; Barik, Rajib; Mandal, Mahitosh; Pal, Tapan Kumar

    2014-01-02

    Paclitaxel, a potential anticancer agent against solid tumors has been restricted from its oral use due to poor water solubility as well as Pgp efflux property. The present study was aimed to improve the oral bioavailability of paclitaxel through development of (o/w) nanoemulsion consisting of Capryol 90 as internal phase with Tween 20 as emulsifier with water as an external phase. Formulations were selected from the nanoemulsion region of pseudo-ternary phase diagrams, formulated by aqueous titration method. The developed nanoemulsion has been characterized by its thermodynamic stability, morphology, droplet size, zeta potential, viscosity where in vitro release was evaluated through dialysis. Paclitaxel nanoemulsion exhibited thermodynamical stability with low viscosity, nano-sized oil droplets in water with low poly-dispersity index. The shelf life of the paclitaxel nanoemulsion was found to be approximately 2.38 years. Increased permeability through the Caco-2 cell monolayer and decreased efflux is great advantageous for nanoemulsion formulation. The effects of paclitaxel nanoemulsion on breast cancer cell proliferation, morphology and DNA fragmentation were analyzed in vitro which showed significant anti-proliferation and decreased IC50 values in nanoemulsion group which may be due to enhanced uptake of paclitaxel through the oil core. Moreover, the absolute oral bioavailability and sustained release profile of the paclitaxel nanoemulsion evaluated in mouse model was found to improve up to 55.9%. The concentration of paclitaxel in mice plasma was determined by our validated LC-MS/MS method. By reviewing the significant outcome of the present investigation based on stability study, Caco-2 permeability, cell proliferative assay and pharmacokinetic profile it may be concluded that the oral nanoemulsion has got encouraging advantages over the presently available formulations of this injectable chemotherapeutic drug. Copyright © 2013 Elsevier B.V. All rights

  20. Sustained-release effervescent floating matrix tablets of baclofen: development, optimization and in vitro-in vivo evaluation in healthy human volunteers

    Directory of Open Access Journals (Sweden)

    YM Rao

    2011-07-01

    Full Text Available "n  Background and the purpose of the study: Baclofen, a centrally acting skeletal muscle relaxant, is indicated in the long-term treatment of spasticity. It is difficult to formulate baclofen sustained release dosage forms because its absorption on arrival to colon (or even before is low or nonexistent. In the present investigation efforts were made to improve the bioavailability of baclofen by increasing the residence time of the drug through sustained-release matrix tablet formulation via gastroretentive mechanism. "n  Methods: Tablets were prepared by wet granulation technique. The influence of gas generating and gel forming agents, amount of baclofen and total weight of tablet on physical properties, in vitro buoyancy, floating lag time, drug release, DSC, X-ray studies were investigated. The release mechanisms were explored and explained by applying zero order, first order, Higuchi and Korsmeyer equations. The selected formulations were subjected to stability study for the period of three months. "n  Results: For all formulations, kinetics of drug release from tablet followed Higuchi's square root of time kinetic treatment heralding diffusion as predominant mechanism of drug release. Formulations containing 20 mg and 40 mg (F-1 and F-7 showed similar release profiles. There was no significant change in the selected formulations, when subjected to accelerated stability conditions over a period of three months. X-ray imaging in six healthy human volunteers revealed a mean gastric retention period of 5.50±0.7 hrs for the selected formulation. "n  Conclusion:Stable, sustained release effervescent floating matrix tablets of baclofen could be prepared by wet granulation technique.

  1. Potential Use of Polyvinyl Acetate-Polyvinylpyrrolidone Mixture for the Development of Atenolol Sustained Release Matrix Tablets: Optimization of Formulation through in Vitro-in Vivo Assessment Study.

    Science.gov (United States)

    Owayez, Ali Saeed; Abd El-Ghany, Galal Mahmoud; Abu Hashim, Irhan Ibrahim

    2017-01-01

    The objective of this study was to develop sustained release matrix tablets of atenolol (AT) using different concentrations of polyvinyl acetate-polyvinylpyrrolidone mixture (KSR) (20, 30, or 40%) with various types of fillers such as spray dried lactose (SP.D.L), avicel pH 101 (AV), and emcompress (EMS). The physical characteristics of the prepared tablets were evaluated. Characterization of the optimized formulation was performed using Fourier transform (FT)-IR spectroscopy and differential scanning calorimetry (DSC). Moreover, the in vitro release profiles of AT formulations were investigated in different pH dissolution media. Drug release kinetics and mechanisms were also determined. The results revealed that there was no potential incompatibility of the drug with the polymer. The release profiles of AT were affected by the concentration of KSR, fillers used, and pH of the dissolution media. The drug release kinetic from most of the formulations obeyed Higuchi diffusion model. The selected formulae were investigated for their stability by storage at 30 and 40°C with atmospheric humidity and 75% relative humidity (RH), respectively. The results demonstrated that no change in the physicochemical properties of the tablets stored at 30°C/atmospheric RH in comparison with some changes at 40°C/75% RH. Finally, the in vivo study provided an evidence that the optimized AT tablet containing 40% KSR and SP.D.L exhibited prominent higher oral bioavailability and more efficient sustained-release effect than the drug alone or the commercial tablet product. It is noteworthy that KSR could be considered as a promising useful release retardant for the production of AT sustained release matrix tablets.

  2. Poly(glycerol adipate-co-ω-pentadecalactone) spray-dried microparticles as sustained release carriers for pulmonary delivery.

    Science.gov (United States)

    Tawfeek, Hesham; Khidr, Sayed; Samy, Eman; Ahmed, Sayed; Murphy, Mark; Mohammed, Afzaal; Shabir, Anjum; Hutcheon, Gillian; Saleem, Imran

    2011-09-01

    The aim of this work was to optimize biodegradable polyester poly(glycerol adipate-co-ω-pentadecalactone), PGA-co-PDL, microparticles as sustained release (SR) carriers for pulmonary drug delivery. Microparticles were produced by spray drying directly from double emulsion with and without dispersibility enhancers ((L)-arginine and (L)-leucine) (0.5-1.5%w/w) using sodium fluorescein (SF) as a model hydrophilic drug. Spray-dried microparticles without dispersibility enhancers exhibited aggregated powders leading to low fine particle fraction (%FPF) (28.79 ± 3.24), fine particle dose (FPD) (14.42 ± 1.57 μg), with a mass median aerodynamic diameter (MMAD) 2.86 ± 0.24 μm. However, (L)-leucine was significantly superior in enhancing the aerosolization performance ((L-)arginine:%FPF 27.61 ± 4.49-26.57 ± 1.85; FPD 12.40 ± 0.99-19.54 ± 0.16 μg and MMAD 2.18 ± 0.35-2.98 ± 0.25 μm, (L)-leucine:%FPF 36.90 ± 3.6-43.38 ± 5.6; FPD 18.66 ± 2.90-21.58 ± 2.46 μg and MMAD 2.55 ± 0.03-3.68 ± 0.12 μm). Incorporating (L)-leucine (1.5%w/w) reduced the burst release (24.04 ± 3.87%) of SF compared to unmodified formulations (41.87 ± 2.46%), with both undergoing a square root of time (Higuchi's pattern) dependent release. Comparing the toxicity profiles of PGA-co-PDL with (L)-leucine (1.5%w/w) (5 mg/ml) and poly(lactide-co-glycolide), (5 mg/ml) spray-dried microparticles in human bronchial epithelial 16HBE14o- cell lines, resulted in cell viability of 85.57 ± 5.44 and 60.66 ± 6.75%, respectively, after 72 h treatment. The above data suggest that PGA-co-PDL may be a useful polymer for preparing SR microparticle carriers, together with dispersibility enhancers, for pulmonary delivery.

  3. Therapeutic treatment with sustained-release platelet-rich plasma restores blood perfusion by augmenting ischemia-induced angiogenesis and arteriogenesis in diabetic mice.

    Science.gov (United States)

    Bir, Shyamal Chandra; Esaki, Jiro; Marui, Akira; Sakaguchi, Hisashi; Kevil, Christopher G; Ikeda, Tadashi; Komeda, Masashi; Tabata, Yasuhiko; Sakata, Ryuzo

    2011-01-01

    The objective of this investigation was to establish the effectiveness of sustained-release platelet-rich plasma (PRP) on perfusion and neovascularization in diabetic murine hind limb ischemia. After surgery in streptozotocin-induced diabetic mice, the mice were randomly assigned to the following 4 experimental groups: control (C), 100 μl of the sustained-release form of platelet-poor plasma (PPP), 100 μl of the solution form of PRP (PRP-sol), and 100 μl of the sustained-release form of PRP (PRP-sr). Endpoint evaluations were: blood perfusion by laser Doppler perfusion imaging (LDPI), vascular density by anti-vWF, and mature vessel density by anti-smooth muscle actin antibody. This study demonstrated that a sustained release of PRP increases the perfusion of ischemic tissue as measured by LDPI (57 ± 12; 56 ± 9; 72 ± 7, and 98 ± 4 for the C, PPP, PRP-sol, and PRP-sr groups, respectively; p < 0.05), capillary density (151 ± 16; 158 ± 12; 189 ± 39, and 276 ± 39 for groups C, PPP, PRP-sol, and PRP-sr, respectively; p < 0.05), and mature vessel density (28 ± 2; 31 ± 3; 52 ± 10, and 85 ± 13 for the C, PPP, PRP-sol, and PRP-sr groups, respectively; p < 0.05). A sustained release of PRP containing potent angiogenic growth factors restores blood perfusion by stimulating angiogenesis and arteriogenesis. Copyright © 2010 S. Karger AG, Basel.

  4. Effects of bupropion sustained release on task-related EEG alpha activity in smokers: Individual differences in drug response.

    Science.gov (United States)

    Zhu, Jian; Coppens, Ryan P; Rabinovich, Norka E; Gilbert, David G

    2017-02-01

    The mechanisms underlying bupropion's efficacy as an antidepressant and a smoking cessation aid are far from being fully characterized. The present study is the first to examine the effects of bupropion on visuospatial task-related parietal EEG alpha power asymmetry-an asymmetry that has previously been found to be associated with severity of depressive symptoms (i.e., the more depressive symptoms, the greater alpha power in the right vs. left parietal area [Henriques & Davidson, 1997; Rabe, Debener, Brocke, & Beauducel, 2005]). Participants, all of whom were smokers and none of whom were clinically depressed, were randomly assigned to the Placebo group (n = 79) or Bupropion group (n = 31) in a double-blind study. EEG during the performance of the visuospatial task was collected before and after 14 days on placebo or bupropion sustained-release capsules. Relative to the Placebo group, the Bupropion group (especially, the Bupropion subgroup who had a positive right versus left parietal alpha power asymmetry at pretreatment) had a reduction in the parietal alpha asymmetry (driven largely by a decrease in right parietal alpha power). These findings support the hypothesis that bupropion can induce changes in parietal EEG asymmetry that have been shown in previous literature to be associated with a reduction in depressive states and traits. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  5. Freeze-dried mucoadhesive polymeric system containing pegylated lipoplexes: Towards a vaginal sustained released system for siRNA.

    Science.gov (United States)

    Furst, Tania; Dakwar, George R; Zagato, Elisa; Lechanteur, Anna; Remaut, Katrien; Evrard, Brigitte; Braeckmans, Kevin; Piel, Geraldine

    2016-08-28

    Topical vaginal sustained delivery of siRNA presents a significant challenge due to the short residence time of formulations. Therefore, a drug delivery system capable to adhere to the vaginal mucosa is desirable, as it could allow a prolonged delivery and increase the effectiveness of the therapy. The aim of this project is to develop a polymeric solid mucoadhesive system, loaded with lipoplexes, able to be progressively rehydrated by the vaginal fluids to form a hydrogel and to deliver siRNA to vaginal tissues. To minimize adhesive interactions with vaginal mucus components, lipoplexes were coated with different derivatives of polyethylene glycol: DPSE-PEG2000, DPSE-PEG750 and ceramide-PEG2000. Based on stability and diffusion properties in simulated vaginal fluids, lipoplexes containing DSPE-PEG2000 were selected and incorporated in hydroxyethyl cellulose (HEC) hydrogels. Solid systems, called sponges, were then obtained by freeze-drying. Sponges meet acceptable mechanical characteristics and their hardness, deformability and mucoadhesive properties are not influenced by the presence of lipoplexes. Finally, mobility and stability of lipoplexes inside sponges rehydrated with vaginal mucus, mimicking in situ conditions, were evaluated by advanced fluorescence microscopy. The release rate was found to be influenced by the HEC concentration and consequently by the viscosity after rehydration. This study demonstrates the feasibility of entrapping pegylated lipoplexes into a solid matrix system for a prolonged delivery of siRNA into the vagina. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Sustained-release morphine sulfate with sequestered naltrexone for moderate to severe pain: a new opioid analgesic formulation and beyond.

    Science.gov (United States)

    Ruan, Xiulu

    2011-05-01

    Opioid usage during chronic nonmalignant pain has increased substantially over the past two decades. Prescription opioids have become the second most misused drug in the USA and prescription opioid abuse has escalated into a widespread public health problem. It is hoped that abuse-deterrent opioid formulations will take an important role in reducing opioid abuse, misuse and diversion. Embeda (sustained-release morphine sulfate with sequestered naltrexone)represents a new opioid formulation with an intended abuse-deterrent feature, now available on the market. Although Embeda seems to be a successful formulation by passing the efficacy trial, safety trial, pharmacokinetic study and abuse liability study, etc., it will require some long-term prospective epidemiological studies to substantiate fully its abuse-deterrent benefit. Embeda represents a new opioid formulation, adding to our arsenal to treat moderate to severe pain and playing its potential role in discouraging opioid abuse, misuse and diversion. Faced with an overwhelmingly expanding public health burden due to prescription opioid abuse, clinicians should always keep in mind the balance of maximizing pain relief and minimizing prescription opioid abuse. © 2011 Informa UK, Ltd

  7. Antinociceptive effects of sustained-release buprenorphine in a model of incisional pain in rats (Rattus norvegicus).

    Science.gov (United States)

    Chum, Helen H; Jampachairsri, Katechan; McKeon, Gabriel P; Yeomans, David C; Pacharinsak, Cholawat; Felt, Stephen A

    2014-03-01

    Effective management of postoperative pain is an essential component of the care and welfare of laboratory animals. A sustained-release formulation of buprenorphine (Bup-SR) has recently been introduced to the veterinary market and has been reported to provide analgesia for as long as 72 h. Using evoked mechanical and thermal hypersensitivity tests, we here evaluated the antinociceptive effects of Bup-SR in a model of incisional pain in rats. Paw withdrawal responses were obtained before and 1 through 4 d after surgery. Rats are assigned to receive Bup-SR (0.3, 1.2, or 4.5 mg/kg SC once) or buprenorphine HCl (Bup HCl, 0.05 mg/kg SC twice daily for 3 d). Responses to mechanical and thermal stimuli in the 1.2 and 4.5 Bup-SR groups did not differ from those of rats in the Bup HCl group. Thermal latency on day 3 in rats that received 0.3 mg/kg Bup-SR was significantly different from baseline, indicating that this dose effectively decreased thermal hypersensitivity for at least 48 h. Marked sedation occurred in rats in the 4.5 Bup-SR group. Our findings indicate that Bup-SR at 0.3 or 1.2 mg/kg SC is effective in minimizing hypersensitivity with minimal sedation for at least 48 h (thermal hypersensitivity) and 72 h, respectively, in the incisional pain model in rats.

  8. Investigation of in situ gelling alginate formulations as a sustained release vehicle for co-precipitates of dextromethrophan and Eudragit S 100

    Directory of Open Access Journals (Sweden)

    Maghraby Gamal Mohamed El

    2014-03-01

    Full Text Available Alginate vehicles are capable of forming a gel matrix in situ when they come into contact with gastric medium in the presence of calcium ions. However, the gel structure is pH dependent and can break after gastric emptying, leading to dose dumping. The aim of this work was to develop modified in situ gelling alginate formulations capable of sustaining dextromethorphan release throughout the gastrointestinal tract. Alginate solution (2 %, m/m was used as a vehicle for the tested formulations. Solid matrix of the drug and Eudragit S 100 was prepared by dissolving the drug and polymer in acetone. The organic solvent was then evaporated and the deposited solid matrix was micronized, sieved and dispersed in alginate solution to obtain candidate formulations. The release behavior of dextromethorphan was monitored and evaluated in a medium simulating the gastric and intestinal pH. Drug-polymer compatibility and possible solid-state interactions suggested physical interaction through hydrogen bonding between the drug and the polymer. A significant decrease in the rate and extent of dextromethorphan release was observed with increasing Eudragit S 100 concentration in the prepared particles. Most formulations showed sustained release profiles similar to that of a commercial sustained-release liquid based on ion exchange resin. The release pattern indicated strict control of drug release both under gastric and intestinal conditions, suggesting the potential advantage of using a solid dispersion of drug-Eudragit S 100 to overcome the problem of dose dumping after the rupture of the pH dependent alginate gels

  9. Angiogenic properties of sustained release platelet-rich plasma: characterization in-vitro and in the ischemic hind limb of the mouse.

    Science.gov (United States)

    Bir, Shyamal Chandra; Esaki, Jiro; Marui, Akira; Yamahara, Kenichi; Tsubota, Hideki; Ikeda, Tadashi; Sakata, Ryuzo

    2009-10-01

    While single growth factor has limitation to induce optimal neovascularization, platelet-rich plasma (PRP) is an autologous reserver of various growth factors. However, little is known about the mechanism of PRP-related neovascularization.The objective of this investigation was to characterize the angiogenic and growth factor content of PRP and to determine, in vitro, its effect on endothelial cell proliferation. Additionally, this experiment sought to determine the effectiveness of different compositions of PRP (solution versus sustained release) on perfusion and neovascularization in a murine model of hind limb ischemia. Different growth factors were measured by enzyme-linked immunosorbent assay (ELISA). In vivo study, we used gelatin hydrogel as a sustained release carrier for growth factors in PRP. We induced hind limb ischemia by excising right femoral artery in wild type C57BL6 mice. After surgery, mice were randomly assigned to four experimental groups; control (C), 100 muL of sustained release form of platelet-poor plasma (PPP), 100 muL of solution form of PRP (PRP-sol), 100 muL of sustained release form of PRP (PRP-sr); each formulation was administered via an intramuscular injection to the ischemic hind limb. Endpoint evaluations were blood perfusion by laser Doppler perfusion image, vascular density by anti Von Willebrand factor (vWF), and mature vessel density by anti smooth muscle actin (SMA) antibody. Green fluorescent protein (GFP+) transgenic mice were generated by transplantation of bone marrow derived mononuclear cells to wild type C57BL6 mice, and finally CD34+ cell in the ischemic site of transgenic mice was detected by staining with anti-CD34 antibody. In vitro study showed that PRP containing different growth factors induces endothelial cell proliferation and capillary tube formation. In vivo study demonstrated that sustained release of PRP increased perfusion of ischemic tissue as measured by laser Doppler perfusion imaging (LDPI) (57 +/- 12

  10. A (polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer)-dispersed sustained-release tablet for imperialine to simultaneously prolong the drug release and improve the oral bioavailability.

    Science.gov (United States)

    Lin, Qing; Fu, Yu; Li, Jia; Qu, Mengke; Deng, Li; Gong, Tao; Zhang, Zhirong

    2015-11-15

    Imperialine, extracted from Bulbus Fritillariae Cirrhosae, is an efficient antitussive and expectorant medicine. However, its short half-life and stomach degradation limited imperialine from further clinical use. The current study was conducted to develop a sustained-release tablet for imperialine both to prolong absorption time and to improve the oral bioavailability of the drug. The tablets were prepared by a direct compression method formulated on optimized solid dispersion (SD) for imperialine based on polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (Soluplus(®)) with imperialine/Soluplus(®) ratio of 1:8 (w/w). In order to obtain the optimized formulation, factors that affected the drug release were investigated by in vitro dissolution studies in the media of pH1.2, 5.8, 7.0 and 7.4. Powder X-ray diffraction and scanning electron microscope confirmed that the imperialine in SD was amorphous instead of crystalline, and still stayed amorphous even after the direct compression. And besides, pharmacokinetic study in Beagle dogs was performed to inspect the in vivo sustained release. Plasma concentration-time curves and pharmacokinetic parameters were gained. As a result, the Cmax of imperialine was one-fold reduced and Tmax was two-fold prolonged, and the mean AUC0-24 was expressed as 89.581±21.243μgh/L, which showed that the oral bioavailability of imperialine was 2.46-fold improved. Moreover, the in vitro-in vivo correlation was recommended to carry out, demonstrating the percentages of drug release in vitro were well-correlated with the absorptive fraction in vivo with the correlation coefficients above 0.9900. By mathematically modeling and moment imaging of the drug release, Peppas equation was selected as the most fitted model for the sustained-release tablets with the diffusional coefficient in the range of 0.59-0.62, indicating the release of imperialine from the sustained-release tablets was an anomalous process involving

  11. Is gentamycin delivery via sustained-release vehicles a safe and effective treatment for refractory Meniere's disease? A critical analysis of published interventional studies.

    Science.gov (United States)

    Vlastarakos, Petros V; Iacovou, Emily; Nikolopoulos, Thomas P

    2017-03-01

    The aim of this study is to review the literature on sustained-release vehicles delivering gentamycin in the inner ear of patients suffering from Meniere's disease (MD), and critically assess their respective clinical effectiveness and safety. A systematic literature review was conducted in Medline and other database sources until January 2016, along with critical analysis of pooled data. Overall, six prospective and four retrospective studies were systematically analyzed. The total number of treated patients was 320. A 2 year patient follow up was only reported in 40 % of studies. Inner ear gentamycin delivery using sustained-release vehicles is associated with improved vertigo control (strength of recommendation B), and quality of life (strength of recommendation B) in MD sufferers. In addition, dynamic-release devices seem to achieve high rates of improvement in the appearance of tinnitus (65.4 %) and aural pressure (76.2 %). By contrast, percentages of complete and partial hearing loss appear unacceptably high (31.08 and 23.38 % of patients, respectively), compared to historical data involving simple intratympanic gentamycin injections. Sustained-release vehicles for gentamycin delivery may have a role in the management of MD patients who have previously failed intratympanic gentamycin injections, or those who have already lost serviceable hearing. Their use as first line treatment over single intratympanic injections for all MD patients, who do not respond to conservative treatment should be discouraged.

  12. Exploring polyvinylpyrrolidone in the engineering of large porous PLGA microparticles via single emulsion method with tunable sustained release in the lung: In vitro and in vivo characterization.

    Science.gov (United States)

    Ni, Rui; Muenster, Uwe; Zhao, Jing; Zhang, Lan; Becker-Pelster, Eva-Maria; Rosenbruch, Martin; Mao, Shirui

    2017-03-10

    Sustained pulmonary drug delivery is regarded as an effective strategy for local treatment of chronic lung diseases. Despite of the progress made so far, there remains a need for respirable drug loaded porous microparticles, where porosity of the microparticles can be readily engineered during the preparation process, with tunable sustained drug release upon lung deposition. In this work, polyvinyl pyrrolidone (PVP) was used as a novel porogen to engineer PLGA-based large porous particles (LPPs) using single emulsion method, with fine tuning of the porosity, sustained drug release both in vitro and in vivo. Using cinaciguat as the model drug, influence of PVP content and PLGA type on the properties of the LPPs was characterized, including geometric particle size, drug encapsulation efficiency, tap density, theoretical and experimental aerodynamic particle size, specific surface area, morphology, and in vitro drug release. Solid state of cinaciguat in the LPPs was studied based on DSC and X-ray analysis. LPPs retention in the rat lung was carried out using bronchoalveolar lavage fluid method. Raw 264.7 macrophage cells were used for LPPs uptake study. Pharmacodynamic study was performed in mini-pigs in a well-established model of pulmonary arterial hypertension (thromboxane challenge). It was demonstrated that porosity of the LPPs is tunable via porogen content variation. Cinaciguat can be released from the LPP in a controlled manner for over 168h. Significant reduction of macrophage phagocytosis was presented for LPPs. Furthermore, LPPs was found to have extended retention time (~36h) in the rat lung and accordingly, sustained pharmacodynamics effect was achieved in mini-pig model. Taken together, our results demonstrated that this simple PLGA based LPPs engineering using single emulsion method with PVP as porogen may find extensive application for the pulmonary delivery of hydrophobic drugs to realize tunable sustained effect with good safety profile. Copyright

  13. Lenghty reverse poly(butylene oxide)-poly(ethylene oxide)-poly(butylene oxide) polymeric micelles and gels for sustained release of antifungal drugs.

    Science.gov (United States)

    Figueroa-Ochoa, Edgar B; Villar-Alvarez, Eva M; Cambón, Adriana; Mistry, Dharmista; Llovo, José; Attwood, David; Barbosa, Silvia; Soltero, J F Armando; Taboada, Pablo

    2016-08-20

    In this work, we present a detailed study of the potential application of polymeric micelles and gels of four different reverse triblock poly(butylene oxide)-poly(ethylene oxide)-poly(butylene oxide) copolymers (BOnEOmBOn, where n denotes the respective block lengths), specifically BO8EO90BO8, BO14EO378BO14, BO20EO411BO20 and BO21EO385BO21, as effective drug transport nanocarriers. In particular, we tested the use of this kind of polymeric nanostructures as reservoirs for the sustained delivery of the antifungals griseofulvin and fluconazole for oral and topical administration. Polymeric micelles and gels formed by these copolymers were shown to solubilize important amounts of these two drugs and to have a good stability in physiologically relevant conditions for oral or topical administration. These polymeric micellar nanocarriers were able to release drugs in a sustained manner, being the release rate slower as the copolymer chain hydrophobicity increased. Different sustained drug release profiles were observed depending on the medium conditions. Gel nanocarriers were shown to display longer sustained release rates than micellar formulations, with the existence of a pulsatile-like release mode under certain solution conditions as a result of their inner network structure. Certain bioadhesive properties were observed for the polymeric physical gels, being moderately tuned by the length and hydrophobicity of the polymeric chains. Furthermore, polymeric gels and micelles showed activity against the yeast Candida albicans and the mould demartophytes (Trichophyton rubrum and Microsporum canis) and, thus, may be useful for the treatment of different cutaneous fungal infections. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Bypassing the EPR effect with a nanomedicine harboring a sustained-release function allows better tumor control.

    Science.gov (United States)

    Shen, Yao An; Shyu, Ing Luen; Lu, Maggie; He, Chun Lin; Hsu, Yen Mei; Liang, Hsiang Fa; Liu, Chih Peng; Liu, Ren Shyan; Shen, Biing Jiun; Wei, Yau Huei; Chuang, Chi Mu

    2015-01-01

    The current enhanced permeability and retention (EPR)-based approved nanomedicines have had little impact in terms of prolongation of overall survival in patients with cancer. For example, the two Phase III trials comparing Doxil(®), the first nanomedicine approved by the US Food and Drug Administration, with free doxorubicin did not find an actual translation of the EPR effect into a statistically significant increase in overall survival but did show less cardiotoxicity. In the current work, we used a two-factor factorial experimental design with intraperitoneal versus intravenous delivery and nanomedicine versus free drug as factors to test our hypothesis that regional (intraperitoneal) delivery of nanomedicine may better increase survival when compared with systemic delivery. In this study, we demonstrate that bypassing, rather than exploiting, the EPR effect via intraperitoneal delivery of nanomedicine harboring a sustained-release function demonstrates dual pharmacokinetic advantages, producing more efficient tumor control and suppressing the expression of stemness markers, epithelial-mesenchymal transition, angiogenesis signals, and multidrug resistance in the tumor microenvironment. Metastases to vital organs (eg, lung, liver, and lymphatic system) are also better controlled by intraperitoneal delivery of nanomedicine than by standard systemic delivery of the corresponding free drug. Moreover, the intraperitoneal delivery of nanomedicine has the potential to replace hyperthermic intraperitoneal chemotherapy because it shows equal efficacy and lower toxicity. In terms of efficacy, exploiting the EPR effect may not be the best approach for developing a nanomedicine. Because intraperitoneal chemotherapy is a type of regional chemotherapy, the pharmaceutical industry might consider the regional delivery of nanomedicine as a valid alternative pathway to develop their nanomedicine(s) with the goal of better tumor control in the future.

  15. Pharmacokinetics and Paw Withdrawal Pressure in Female Guinea Pigs (Cavia porcellus) Treated with Sustained-Release Buprenorphine and Buprenorphine Hydrochloride.

    Science.gov (United States)

    Smith, Brian J; Wegenast, Daniel J; Hansen, Ryan J; Hess, Ann M; Kendall, Lon V

    2016-11-01

    Providing appropriate analgesia is essential in minimizing pain and maintaining optimal animal care and welfare in laboratory animals. Guinea pigs are common animal models in biomedical research, often requiring analgesic support. Here we evaluated the pharmacokinetics and efficacy of a sustained-release formulation of buprenorphine (Bup-SR) in this species. Guinea pigs (n = 7 each group) received either Bup-HCl (0.05 mg/kg BID for 3 d) or Bup-SR (0.3 mg/kg once). Plasma collection and measurement of paw-withdrawal pressure (PWP) was conducted at 0, 1, 3, 6, 12, 26, 48, and 72 h after treatment. Plasma levels of Bup-HCl peaked at 2331 pg/mL at 1 h after administration and declined to 165 pg/mL by 12 h. Plasma concentrations of Bup-SR peaked at 1344 pg/mL at 26 h after administration and declined to 429 pg/mL by 48 h. The PWP of the Bup-HCltreated guinea pigs peaked at 674 g at 1 h and declined to 402 g at 6 h, whereas that of Bup-SRtreated guinea pigs at 1 h was 361 g, 555 g at 6 h (significantly higher than that after Bup-HCl), and peaked at 680 g at 12 h. The PWP of both treatments was similar from 24 to 72 h and ranged from 348 to 450 g. The plasma concentration and PWP showed good correlation. These results suggest that Bup-SR provides consistent analgesia equivalent to that of Bup-HCl for a prolonged period of time and that Bup-SR is an alternative method of analgesia in guinea pigs.

  16. Effects of sustained-release trimetazidine on chronically dysfunctional myocardium of ischemic dilated cardiomyopathy - Six months follow-up result.

    Science.gov (United States)

    Momen, A; Ali, M; Karmakar, P K; Ali, M Z; Haque, A; Khan, M R; Khalil, M I; Hossain, M S; Huda, R M; Goni, M N

    Ischemic cardiomyopathy is a growing burden in third world countries. So far, benefits of trimetazidine in this group of patients have been suggested by clinical trials mainly conducted in Europe. We evaluated the effect of trimetazidine on ischemic dilated cardiomyopathy in our population. 98 patients (aged 58.5±9.2 years), admitted with decompensated heart failure with previous history of MI and/or documentation of significant CAD with previous CAG, were chosen for the study. Patients were randomized into two groups - one provided with trimetazidine 35mg sustained released tablet, twice daily and the other with a placebo, along with other conventional medications. Patients were included if they had dilated LV (LVIDd>57mm) and left ventricular ejection fraction (LVEF) ≤40%. After 6 months, significantly higher number of patients in trimetazidine group were in NYHA class I (22% vs. 8%, p=0.03) and class II (56% vs. 34%, p=0.01); higher number of patients in placebo group were in NYHA class III class IV. Anginal episodes and use of sublingual nitrate per week were significantly lower in the trimetazidine group. Left ventricular diastolic dimension (59.7±5.2 vs. 65.1±6.1, p=0.001) was significantly different in the two groups as was the increase of LVEF (11% vs. 5.6%, p=0.001). Hospitalization for worsening heart failure was significantly lower in trimetazidine group (13 vs. 22, p=0.047). Trimetazidine seems to be beneficial in patients with ischemic dilated cardiomyopathy in South Asian population and larger scale study with extended follow-up is needed. Copyright © 2016 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.

  17. Pregnancy success of lactating Holstein cows after a single administration of a sustained-release formulation of recombinant bovine somatotropin

    Directory of Open Access Journals (Sweden)

    Gutiérrez CG

    2008-06-01

    Full Text Available Abstract Background Results regarding the use of bovine somatotropin for enhancing fertility in dairy cattle are variable. Here, the hypothesis was tested that a single injection of a sustained-release preparation of bovine somatotropin (bST during the preovulatory period would improve pregnancy success of lactating dairy cows at first service. Results The first experiment was conducted in a temperate region of Mexico. Cows inseminated following natural estrus or timed artificial insemination were given a single injection of bST or a placebo injection at insemination (n = 100 cows per group. There was no significant difference between bST and control groups in the proportion of inseminated cows diagnosed pregnant (29 vs 31% pregnant. The second experiment was performed during heat stress in Florida. Cows were subjected to an ovulation synchronization regimen for first insemination. Cows treated with bST received a single injection at 3 days before insemination. Controls received no additional treatment. As expected, bST did not increase vaginal temperature. Treatment with bST did not significantly increase the proportion of inseminated cows diagnosed pregnant although it was numerically greater for the bST group (24.2% vs 17.8%, 124–132 cows per group. There was a tendency (p = 0.10 for a smaller percent of control cows to have high plasma progesterone concentrations (≥ 1 ng/ml at Day 7 after insemination than for bST-treated cows (72.6 vs 81.1%. When only cows that were successfully synchronized were considered, the magnitude of the absolute difference in the percentage of inseminated cows that were diagnosed pregnant between bST and control cows was reduced (24.8 vs 22.4% pregnant for bST and control. Conclusion Results failed to indicate a beneficial effect of bST treatment on fertility of lactating dairy cows.

  18. Clinical Efficacy of Sustained-Release Buprenorphine with Meloxicam for Postoperative Analgesia in Beagle Dogs Undergoing Ovariohysterectomy

    Science.gov (United States)

    Nunamaker, Elizabeth A; Stolarik, DeAnne F; Ma, Junli; Wilsey, Amanda S; Jenkins, Gary J; Medina, Chris L

    2014-01-01

    The goal of the current study was to compare the efficacy, adverse effects, and plasma buprenorphine concentrations of sustained-release buprenorphine (SRB) and buprenorphine after subcutaneous administration in dogs undergoing ovariohysterectomy. In a prospective, randomized, blinded design, 20 healthy adult female Beagle dogs underwent routine ovariohysterectomy and received multimodal analgesia consisting of meloxicam and one of two buprenorphine formulations. Dogs were randomly assigned to receive either SRB (0.2 mg/kg SC, once) or buprenorphine (0.02 mg/kg SC every 12 h for 3 d). Blinded observers assessed all dogs by using sedation scores, pain scores, temperature, HR, RR, and general wellbeing. Dogs were provided rescue analgesia with 0.02 mg/kg buprenorphine SC if the postoperative pain score exceeded a predetermined threshold. Blood samples were collected, and mass spectrometry was used to determine plasma buprenorphine concentrations. Data were analyzed with a linear mixed model and Tukey–Kramer multiple comparison. Age, body weight, anesthetic duration, surgical duration, sevoflurane concentration, and cardiorespiratory variables did not differ significantly between groups. Dogs in both formulation groups had comparable postoperative sedation and pain scores. One dog from each formulation group had breakthrough pain requiring rescue analgesia. Plasma buprenorphine concentrations remained above a hypothesized therapeutic concentration of 0.6 ng/mL for 136.0 ± 11.3 and 10.67 ± 0.84 h for SRB and buprenorphine, respectively. Based on the results of this study, multimodal analgesic regimens consisting of meloxicam and either buprenorphine or SRB are equally efficacious in managing pain associated with an ovariohysterectomy and show comparable side effects. PMID:25255072

  19. Pharmacokinetics of a Sustained Release Formulation of Buprenorphine After Intramuscular and Subcutaneous Administration to American Kestrels ( Falco sparverius ).

    Science.gov (United States)

    Guzman, David Sanchez-Migallon; Knych, Heather K; Olsen, Glenn H; Paul-Murphy, Joanne R

    2017-06-01

    Previous studies have validated the clinical use of opioids with μ-receptor affinities for pain management in raptors. Buprenorphine appears to have a longer duration of action and minimal adverse effects when compared to other opioids in American kestrels ( Falco sparverius ). To determine the pharmacokinetics of a sustained release formulation of buprenorphine in kestrels, we administered a commercially available product (Buprenorphine SR-LAB; Wildlife Pharmaceuticals, Windsor, CO, USA) intramuscularly and subcutaneously to adult kestrels in a partial-crossover experimental design study. A total of 12 birds (6 males and 6 females) were assigned randomly to 3 groups of 4 birds each. A single dose of Buprenorphine SR-LAB (1.8 mg/kg) was administered intramuscularly (IM), and blood samples were collected at 0.25, 3, and 24 hours (n = 4); 1, 6, and 48 hours (n = 4); and 2, 12, and 72 hours (n = 4) after drug administration. Plasma buprenorphine concentrations were measured by tandem liquid chromatography-mass spectrometry. Pharmacokinetic parameters were determined by use of least squares linear regression and noncompartmental analysis of naïve pooled data. After 1 year, the same dose of buprenorphine was administered subcutaneously (SC) to 12 birds divided into 3 groups as previously, and blood samples were collected at the same times after drug administration. Maximum plasma buprenorphine concentration was measured at 15 minutes after IM and SC administration. Mean plasma buprenorphine concentrations were >1 ng/mL for 48 hours after IM and SC administration. The elimination half-life was 13.5 and 11.1 hours for IM and SC administration, respectively. Depending on the severity and type of pain, adjunctive therapy, and the individual response, Buprenorphine SR-LAB administered at 1.8 mg/kg IM or SC to American kestrels would require administration every 12 to 72 hours to manage pain. Further pharmacodynamic and clinical evaluations are warranted in kestrels and

  20. Efficacy and safety of sustained-release recombinant human growth hormone in Korean adults with growth hormone deficiency.

    Science.gov (United States)

    Kim, Youngsook; Hong, Jae Won; Chung, Yoon-Sok; Kim, Sung-Woon; Cho, Yong-Wook; Kim, Jin Hwa; Kim, Byung-Joon; Lee, Eun Jig

    2014-07-01

    The administration of recombinant human growth hormone in adults with growth hormone deficiency has been known to improve metabolic impairment and quality of life. Patients, however, have to tolerate daily injections of growth hormone. The efficacy, safety, and compliance of weekly administered sustained-release recombinant human growth hormone (SR-rhGH, Declage™) supplement in patients with growth hormone deficiency were evaluated. This trial is 12-week prospective, single-arm, open-label trial. Men and women aged ≥20 years with diagnosed growth hormone deficiency (caused by pituitary tumor, trauma and other pituitary diseases) were eligible for this study. Each subject was given 2 mg (6 IU) of SR-rhGH once a week, subcutaneously for 12 weeks. Efficacy and safety at baseline and within 30 days after the 12th injection were assessed and compared. Score of Assessment of Growth Hormone Deficiency in Adults (AGHDA score) for quality of life and serum IGF-1 level. The IGF-1 level of 108.67±74.03 ng/mL was increased to 129.01±68.37 ng/mL (p=0.0111) and the AGHDA QoL score was decreased from 9.80±6.51 to 7.55±5.76 (p<0.0001) at week 12 compared with those at baseline. Adverse events included pain, swelling, erythema, and warmth sensation at the administration site, but many adverse events gradually disappeared during the investigation. Weekly administered SR-rhGH for 12 weeks effectively increased IGF-1 level and improved the quality of life in patients with GH deficiency without serious adverse events.

  1. Sustained release nitrite therapy results in myocardial protection in a porcine model of metabolic syndrome with peripheral vascular disease.

    Science.gov (United States)

    Bradley, Jessica M; Islam, Kazi N; Polhemus, David J; Donnarumma, Erminia; Brewster, Luke P; Tao, Ya-Xiong; Goodchild, Traci T; Lefer, David J

    2015-07-15

    Metabolic syndrome (MetS) reduces endothelial nitric oxide (NO) bioavailability and exacerbates vascular dysfunction in patients with preexisting vascular diseases. Nitrite, a storage form of NO, can mediate vascular function during pathological conditions when endogenous NO is reduced. The aims of the present study were to characterize the effects of severe MetS and obesity on dyslipidemia, myocardial oxidative stress, and endothelial NO synthase (eNOS) regulation in the obese Ossabaw swine (OS) model and to examine the effects of a novel, sustained-release formulation of sodium nitrite (SR-nitrite) on coronary vascular reactivity and myocardial redox status in obese OS subjected to critical limb ischemia (CLI). After 6 mo of an atherogenic diet, obese OS displayed a MetS phenotype. Obese OS had decreased eNOS functionality and NO bioavailability. In addition, obese OS exhibited increased oxidative stress and a significant reduction in antioxidant enzymes. The efficacy of SR-nitrite therapy was examined in obese OS subjected to CLI. After 3 wk of treatment, SR-nitrite (80 mg · kg(-1) · day(-1) bid po) increased myocardial nitrite levels and eNOS function. Treatment with SR-nitrite reduced myocardial oxidative stress while increasing myocardial antioxidant capacity. Ex vivo assessment of vascular reactivity of left anterior descending coronary artery segments demonstrated marked improvement in vasoreactivity to sodium nitroprusside but not to substance P and bradykinin in SR-nitrite-treated animals compared with placebo-treated animals. In conclusion, in a clinically relevant, large-animal model of MetS and CLI, treatment with SR-nitrite enhanced myocardial NO bioavailability, attenuated oxidative stress, and improved ex vivo coronary artery vasorelaxation.

  2. Extracellular Matrix (ECM Multilayer Membrane as a Sustained Releasing Growth Factor Delivery System for rhTGF-β3 in Articular Cartilage Repair.

    Directory of Open Access Journals (Sweden)

    Soon Sim Yang

    Full Text Available Recombinant human transforming growth factor beta-3 (rhTGF-β3 is a key regulator of chondrogenesis in stem cells and cartilage formation. We have developed a novel drug delivery system that continuously releases rhTGF-β3 using a multilayered extracellular matrix (ECM membrane. We hypothesize that the sustained release of rhTGF-β3 could activate stem cells and result in enhanced repair of cartilage defects. The properties and efficacy of the ECM multilayer-based delivery system (EMLDS are investigated using rhTGF-β3 as a candidate drug. The bioactivity of the released rhTGF-ß3 was evaluated through chondrogenic differentiation of mesenchymal stem cells (MSCs using western blot and circular dichroism (CD analyses in vitro. The cartilage reparability was evaluated through implanting EMLDS with endogenous and exogenous MSC in both in vivo and ex vivo models, respectively. In the results, the sustained release of rhTGF-ß3 was clearly observed over a prolonged period of time in vitro and the released rhTGF-β3 maintained its structural stability and biological activity. Successful cartilage repair was also demonstrated when rabbit MSCs were treated with rhTGF-β3-loaded EMLDS ((+ rhTGF-β3 EMLDS in an in vivo model and when rabbit chondrocytes and MSCs were treated in ex vivo models. Therefore, the multilayer ECM membrane could be a useful drug delivery system for cartilage repair.

  3. A novel strategy to design sustained-release poorly water-soluble drug mesoporous silica microparticles based on supercritical fluid technique.

    Science.gov (United States)

    Li-Hong, Wang; Xin, Che; Hui, Xu; Li-Li, Zhou; Jing, Han; Mei-Juan, Zou; Jie, Liu; Yi, Liu; Jin-Wen, Liu; Wei, Zhang; Gang, Cheng

    2013-09-15

    The organic solvent solution immersion method was often used to achieve the loading of the drugs into mesoporous silica, but the drugs that have loaded into the pores of the mesoporous silica would inevitable migrate from the inside to the external surface or near the outside surface during the process of drying. Hence, it often leads to the pores of mesoporous materials not be fully utilized, and results in a low drug loading efficiency and a fast releasing rate. The purpose of this study was to develop a novel drug loading strategy to avoid soluble component migration during the process of drying, then, to prepare poorly water-soluble drug mesoporous silica microparticles with higher drug loading efficiency and longer sustained-release time. Ibuprofen was used as model drug. The microparticles were prepared by a novel method based on mesoporous silica and supercritical fluid (SCF) technique. The drug-loaded mesoporous silica microparticles prepared by SCF technique were analyzed by thermogravimetric analysis (TGA), N2 adsorption/desorption, scanning electron microscopy (SEM), powder X-ray diffraction (XRD) and differential scanning calorimetry (DSC). In vitro releasing study was used to evaluate the sustained-release effect of the drug-loaded microparticles. By virtue of the high diffusibility and the high dissolving capacity of the supercritical carbon dioxide (SCF-CO2), the poorly water-soluble drugs, ibuprofen, entered the pores of the mesoporous silica. The amount and the depth of ibuprofen entered the pores of the mesoporous silica by SCF technique were both larger than those by the solution immersion method. It was found that ibuprofen loaded into the mesoporous silica by SCF technique was amorphous and the largest amount of the ibuprofen loaded into the mesoporous silica by SCF technique could reach 386 mg/g (w/w, ibuprofen/SiO2), it was more than that by the solution immersion method. In vitro releasing study showed that the sustained-release effect of

  4. The influence of spray-drying parameters on phase behavior, drug distribution, and in vitro release of injectable microspheres for sustained release.

    Science.gov (United States)

    Meeus, Joke; Lenaerts, Maité; Scurr, David J; Amssoms, Katie; Davies, Martyn C; Roberts, Clive J; Van Den Mooter, Guy

    2015-04-01

    For ternary solid dispersions, it is indispensable to characterize their structure, phase behavior, and the spatial distribution of the dispersed drug as this might influence the release profile and/or stability of these formulations. This study shows how formulation (feed concentration) and process (feed rate, inlet air temperature, and atomizing air pressure) parameters can influence the characteristics of ternary spray-dried solid dispersions. The microspheres considered here consist of a poly(lactic-co-glycolic acid) (PLGA) surface layer and an underlying polyvinylpyrrolidone (PVP) phase. A poorly soluble active pharmaceutical ingredient (API) was molecularly dispersed in this matrix. Differences were observed in component miscibility, phase heterogeneity, particle size, morphology, as well as API surface coverage for selected spray-drying parameters. Observed differences are likely because of changes in the droplet generation, evaporation, and thus particle formation processes. However, varying particle characteristics did not influence the drug release of the formulations studied, indicating the robustness of this approach to produce particles of consistent drug release characteristics. This is likely because of the fact that the release is dominated by diffusion from the PVP layer through pores in the PLGA surface layer and that observed differences in the latter have no influence on the release. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

  5. Blood Pressure Control with a Single-Pill Combination of Indapamide Sustained-Release and Amlodipine in Patients with Hypertension: The EFFICIENT Study

    OpenAIRE

    Jadhav, Uday; Hiremath, Jagdish; Namjoshi, Deepak J.; Gujral, Vinod K.; Tripathi, Kamlakar K.; Siraj, Mohammad; Shamanna, Paramesh; Safar, Michel

    2014-01-01

    OBJECTIVE: Despite antihypertensive treatment, most hypertensive patients still have high blood pressure (BP), notably high systolic blood pressure (SBP). The EFFICIENT study examines the efficacy and acceptability of a single-pill combination of sustained-release (SR) indapamide, a thiazide-like diuretic, and amlodipine, a calcium channel blocker (CCB), in the management of hypertension. METHODS: Patients who were previously uncontrolled on CCB monotherapy (BP≥140/90 mm Hg) or were previousl...

  6. Phytantriol and glyceryl monooleate cubic liquid crystalline phases as sustained-release oral drug delivery systems for poorly water-soluble drugs II. In-vivo evaluation.

    Science.gov (United States)

    Nguyen, Tri-Hung; Hanley, Tracey; Porter, Christopher J H; Larson, Ian; Boyd, Ben J

    2010-07-01

    Lipid-based liquid crystals formed from phytantriol (PHY) and glyceryl monooleate (GMO) retain their cubic-phase structure on dilution in physiologically relevant simulated gastrointestinal media, suggesting their potential application as sustained-release drug-delivery systems for poorly water-soluble drugs. In this study the potential of PHY and GMO to serve as sustained-release lipid vehicles for a model poorly-water-soluble drug, cinnarizine, was assessed and compared to that of an aqueous suspension formulation. Small-angle X-ray scattering was used to confirm the nanostructure of the liquid-crystalline matrix in the presence of the selected model drug, cinnarizine. Oral bioavailability studies were conducted in rats, and disposition of lipid and drug in segments of the gastrointestinal tract was determined over time. Differences in the digestibility and stability of formulations under digestion conditions were investigated using an in-vitro lipolysis model. The oral bioavailability of cinnarizine using the PHY formulation was 41%, compared to 19% for the GMO formulation and 6% for an aqueous suspension. The PHY formulation provided a T(max) for cinnarizine of 33 h, with absorption apparent up to 55 h after administration. In contrast, the T(max) for the GMO formulation was only 5 h. The PHY formulation was retained in the stomach for extended periods of time, with 56% of lipid remaining in the stomach after 24 h, in contrast to less than 1% of the GMO formulation after 8 h, suggesting that gastric retention was a key aspect of the prolonged period of absorption, which correlated with the formulations' relative susceptibility to in-vitro lipolysis and degradation. PHY provides a dramatic sustained-release effect for cinnarizine on oral administration, which is linked to gastric retention of the formulation and its ability to resist digestive processing. Poorly digested liquid crystal lipid formulations therefore offer a novel class of sustained-release

  7. Safety and clinical effectiveness of a compounded sustained-release formulation of buprenorphine for postoperative analgesia in New Zealand White rabbits.

    Science.gov (United States)

    DiVincenti, Louis; Meirelles, Luiz A D; Westcott, Robin A

    2016-04-01

    To determine the clinical effectiveness and safety of a compounded sustained-release formulation of buprenorphine, compared with effects of regular buprenorphine, for postoperative analgesia in rabbits. Blinded randomized controlled clinical trial. 24 purpose-bred adult male New Zealand White rabbits. Rabbits received titanium implants in each tibia as part of another study. Immediately prior to surgery, each rabbit received regular buprenorphine hydrochloride (0.02 mg/kg [0.009 mg/lb], SC, q 12 h for 3 days) or 1 dose of a compounded sustained-release formulation of buprenorphine (0.12 mg/kg [0.055 mg/lb], SC) followed by an equal volume of saline (0.9% NaCl) solution (SC, q 12 h for 3 days) after surgery. For 7 days after surgery, rabbits were evaluated for signs of pain by means of rabbit grimace and activity scoring and for adverse effects. No significant differences were identified between treatment groups in grimace and activity scores at any point. No major adverse effects were detected for either drug. However, 3 rabbits that received regular buprenorphine had pain scores suggestive of moderate to severe pain by the time dose administration was due (ie, within the 12-hour administration interval). No clinically important differences were detected in intraoperative anesthetic or postoperative recovery variables. Sustained-release buprenorphine administered SC at 0.12 mg/kg was at least as effective as regular buprenorphine in providing analgesia for rabbits following orthopedic surgery without any major adverse effects. This sustained-release formulation represents an important alternative for rabbit analgesia with potential to improve rabbit welfare over existing analgesic standards.

  8. Sustained Release Formulation of Primaquine for Prevention of Relapse of Plasmodium vivax Malaria: A Randomized, Double-Blind, Comparative, Multicentric Study

    OpenAIRE

    Pareek, Anil; Chandurkar, Nitin; Gogtay, Nithya; Deshpande, Alaka; Kakrani, Arjun; Kaneria, Mala; Karmakar, Partha; Jain, Arvind; Kochar, Dhanpat; Chogle, Arun; Ray, Arnab

    2015-01-01

    Background. Primaquine is used to eradicate latent Plasmodium vivax parasite from liver, with administration of standard dose daily up to 14 days. We studied efficacy, safety, and tolerability of sustained release (SR) formulation of primaquine in comparison with conventional primaquine in preventing relapse of P. vivax malaria. Methods. Microscopically confirmed cases of P. vivax malaria received chloroquine therapy for three days. Aparasitemic and asymptomatic patients were then randomized ...

  9. Neonatal administration of N-omega-nitro-L-arginine induces permanent decrease in NO levels and hyperresponsiveness to locomotor activity by D-amphetamine in postpubertal rats.

    Science.gov (United States)

    Morales-Medina, Julio César; Mejorada, Alejandro; Romero-Curiel, Alejandra; Aguilar-Alonso, Patricia; León-Chávez, Bertha Alicia; Gamboa, Citlalli; Quirion, Remi; Flores, Gonzalo

    2008-12-01

    Nitric oxide (NO) is associated with dopamine (DA) release. Previously, we demonstrated that rats treated with a non-selective nitric oxide synthase inhibitor, N-omega-nitro-L-arginine (L-NNA) at postnatal days 4-6 (PD4-6) show increased locomotion and disrupt neuronal cytoarchitecture after puberty (PD60). Here, we investigate whether the modulation of NO production in rats at PD4-6 causes long term changes of NO system, its impact on DA innervation, and schizophrenia-like behaviors. NO levels were measured in seven brain areas at PD35, PD60, PD90, and PD120. Autoradiographic studies explored the effect of l-NNA on the expression of D1 and D2 receptors in the caudate-putamen (CPu) and nucleus accumbens (NAcc) at PD60. Locomotor activity was assessed at PD60 using the non-selective DA agonists, amphetamine and apomorphine, and the selective DA receptor agonist [D2, quinpirole; D3, 7-hydroxy-N,N-di-n-propylaminotetralin ((+/-)-7-OH-DPAT)]. L-NNA treatment produced decreases in NO levels in the frontal cortex, striatum, brainstem and cerebellum, while in the occipital cortex changes were observed at PD120. Hippocampus and temporoparietal cortex showed differential levels of NO. Receptor autoradiography revealed increases in D1 receptor levels in the NAcc (shell), while decreases in D2 receptor binding were observed in the CPu and NAcc (core). Amphetamine and quinpirole treatments resulted in increases in locomotion. In contrast, treatment with 7-OH-DPAT produced hypolocomotion at low doses, while increased locomotion was seen at the highest dose. These results show that modulation of NO levels early postnatally (PD4-6) produces long term alteration in NO levels, with possible consequences on DA transmission, and related behaviors relevant to schizophrenia.

  10. Assessing the risk of alcohol-induced dose dumping from sustained-release oral dosage forms: in vitro-in silico approach.

    Science.gov (United States)

    Cvijić, Sandra; Aleksić, Ivana; Ibrić, Svetlana; Parojčić, Jelena

    2017-10-29

    Consumption of alcoholic beverages with sustained-release oral dosage forms may pose a risk to patients due to potential alcohol-induced dose dumping (ADD). Regulatory guidances recommend in vitro dissolution testing to identify the risk of ADD, but the question remains whether currently proposed test conditions can be considered biopredictive. The purpose of this study was to evaluate different dissolution setups to assess ADD, and the potential of combined in vitro-in silico approach to predict drug absorption after concomitant alcohol intake for hydrophilic and lipophilic sustained-release tablets containing ibuprofen or diclofenac sodium. According to the obtained results, the impact of ethanol was predominantly governed by the influence on matrix integrity, with the increase in drug solubility being less significant. Hydrophilic matrix tablets were less susceptible to ADD than lipophilic matrices, although the conclusion on formulation ethanol-vulnerability depended on the employed experimental conditions. In silico predictions indicated that the observed changes in drug dissolution would not result in plasma concentrations beyond therapeutic window, but sustained-release characteristics of the formulations might be lost. Overall, the study demonstrated that in vitro-in silico approach may provide insight into the effect of ADD on drug clinical performance, and serve as a tool for ADD risk assessment.

  11. A Sustained-Release Membrane of Thiazolidinedione-8: Effect on Formation of a Candida/Bacteria Mixed Biofilm on Hydroxyapatite in a Continuous Flow Model

    Directory of Open Access Journals (Sweden)

    Mark Feldman

    2017-01-01

    Full Text Available Thiazolidinediones (TZDs have been found to act as effective quorum sensing quenchers, capable of preventing biofilm formation. Our previous studies demonstrated a profound antibiofilm effect of the TZD derivative thiazolidinedione-8 (S-8, either in solution or incorporated into a sustained-release membrane (SRM-S-8 under batch conditions. In the present study, we used a constant depth film fermenter model in order to investigate the impact of SRM-S-8 on mixed C. albicans-S. mutans biofilm development, under flow conditions. We found that essential parameters of cospecies biofilm maintenance and maturation, such as metabolic activity, biofilm thickness, roughness, extracellular polysaccharides production, and morphology of both pathogens, were altered by SRM-S-8 in the flow system. We propose that prolonged and sustained release of S-8 in a flow-through system allows better penetration of the active agent to deeper layers of the mixed biofilm, thereby increasing its activity against both pathogens. In conclusion, the use of a locally applied sustained-release drug delivery system of S-8 can affect the dental polymicrobial biofilm, resulting in clinical improvements and a better patient compliance.

  12. Improving the encapsulation efficiency and sustained release behaviour of chitosan/β-lactoglobulin double-coated microparticles by palmitic acid grafting.

    Science.gov (United States)

    Yang, Han-Joo; Lee, Pei Sia; Choe, Jaehyeog; Suh, Seokjin; Ko, Sanghoon

    2017-04-01

    Chitosan (CS) was grafted with 0.1 and 0.5% (w/v) palmitic acid (PA) to improve its encapsulation efficiency (EE) and sustained release characteristics when forming CS microparticles. Thereafter, PA-grafted CS (PA-CS) microparticles were coated with denatured β-lactoglobulin (βlg), which forms an outer protective layer. The possibility of hydrophobic interaction with the hydrophobic substances in the CS microparticles increased as the proportion of the grafted PA increased. EE was measured as 64.79, 83.72, and 85.00% for the non-grafted, 0.1, and 0.5% PA-CS microparticles, respectively. In simulated small intestinal conditions, 4.66 and 17.55% of the core material release in the PA-CS microparticles were sustained after 180min by 0.1, and 0.5% PA grafting, respectively. PA grafting enables the sustained release in simulated gastrointestinal fluids by enhancing the hydrophobic interaction between CS and the hydrophobic core material. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. A Sustained-Release Membrane of Thiazolidinedione-8: Effect on Formation of a Candida/Bacteria Mixed Biofilm on Hydroxyapatite in a Continuous Flow Model

    Science.gov (United States)

    Feldman, Mark; Shenderovich, Julia; Lavy, Eran; Friedman, Michael

    2017-01-01

    Thiazolidinediones (TZDs) have been found to act as effective quorum sensing quenchers, capable of preventing biofilm formation. Our previous studies demonstrated a profound antibiofilm effect of the TZD derivative thiazolidinedione-8 (S-8), either in solution or incorporated into a sustained-release membrane (SRM-S-8) under batch conditions. In the present study, we used a constant depth film fermenter model in order to investigate the impact of SRM-S-8 on mixed C. albicans-S. mutans biofilm development, under flow conditions. We found that essential parameters of cospecies biofilm maintenance and maturation, such as metabolic activity, biofilm thickness, roughness, extracellular polysaccharides production, and morphology of both pathogens, were altered by SRM-S-8 in the flow system. We propose that prolonged and sustained release of S-8 in a flow-through system allows better penetration of the active agent to deeper layers of the mixed biofilm, thereby increasing its activity against both pathogens. In conclusion, the use of a locally applied sustained-release drug delivery system of S-8 can affect the dental polymicrobial biofilm, resulting in clinical improvements and a better patient compliance. PMID:29130039

  14. Floating and sustained-release characteristics of effervescent tablets prepared with a mixed matrix of Eudragit L-100-55 and Eudragit E PO.

    Science.gov (United States)

    Bani-Jaber, Ahmad Khaled; Alkawareek, Mahmoud Yousef; Al-Gousous, Jozef Jawad; Abu Helwa, Ahmad Yousef

    2011-01-01

    The aim of this study was to evaluate the influence of Na-bicarbonate as an effervescent agent on the floating and sustained-release characteristics in 0.1 M HCl of tablets made of Eudragit E PO (EE) and/or Eudragit L-100-55 (EL) as matrix formers at different EE:EL weight ratios: 0:100, 25:75, 50:50, 75:25, and 100:0. The tablets were made by direct compression utilizing metronidazole as a model drug. Effervescent tablets with 50EE/50EL (w/w) showed the best floating and sustained drug release properties in the dissolution medium. The corresponding noneffervescent tablets were nonfloating and showed significantly faster drug release. Effervescent tablets with single polymers showed an immediate drug release pattern. These results were explained by Fourier-transform infrared spectroscopy and elemental analysis, which showed strong evidence of interpolyelectrolyte complexation between EE and EL when they were exposed to 0.1 M HCl as an effervescent hybrid matrix, but not as a noneffervescent hybrid matrix. The role of Na-bicarbonate in allowing EE-EL complexation during dissolution was explained as due to raising the pH around EL particles for sufficient polymer ionization and ionic-interaction with the ionized EE. © 2011 Pharmaceutical Society of Japan

  15. Isosorbide-5-mononitrate (5-ISMN) sustained-release pellets prepared by double layer coating for reducing 5-ISMN migration and sublimation.

    Science.gov (United States)

    Li, Guofei; Han, Dandan; Guan, Tingting; Zhao, Xingna; He, Haibing; Tang, Xing

    2010-11-15

    The major aim of this study was to prepare isosorbide-5-mononitrate (5-ISMN) sustained-release pellets and evaluate their stability. The pellets were prepared by extrusion/spheronization, and then the core pellets were coated with ethylcellulose (EC 10cp) and Eudragit(®)NE30D. Here, EC was used as the subcoating agent while Eudragit(®)NE30D acted as the outer-coating agent. 5-ISMN sustained-release pellets as a novel drug delivery system contained the immediate-release portion in the outer-coating layer. Unexpectedly, 5-ISMN was found to migrate from the interior of the pellets to the surface forming needle crystals and exhibited the phenomenon of sublimation, which resulted in a tremendous increase in the release rate. Our research showed that the migration and sublimation of the active ingredient was related to the temperature and humidity. Polyvinylpyrrolidone (PVP K30) can affect the precipitation of 5-ISMN by forming a charge transfer complex between the drug and PVP, while hydroxypropyl methyl cellulose (HPMC E5) had no effect, and confirmed the correctness of this view through photographs and IR spectra. In the investigation of the stability, the results showed that there was no sublimation and migration while the pellets stored at 25°C/60%RH (ambient conditions) and 40°C/75% RH (stress conditions) during a 6-month period. Copyright © 2010 Elsevier B.V. All rights reserved.

  16. [Therapeutic effects and related mechanisms of erythropoietin sustained-release gelatin hydrogel microspheres on a murine model of hindlimb ischemia].

    Science.gov (United States)

    Xiao, J W; Li, L H; Hong, B Z; Xiao, J Q; Wei, D M; Jin, Z

    2016-06-24

    To investigate the therapeutic effects of erythropoietin sustained-release gelatin hydrogel microspheres (EPO-GHM) on a murine model of hindlimb ischemia and related mechanisms. Fifty two ten weeks old male C57BL/6J mice were assigned to 5 groups: sham-operated group (the right femoral artery suture was passed through the right femoral artery but not tied, n=8); saline group (right femoral artery ligation and intramuscular injection of saline at a dose of 4 ml/kg into the right hind limb, n=12); EPO group(right femoral artery ligation and intramuscular injection of EPO at a dose of 5 000 IU/kg into the right hind limb, n=12), empty GHM group (right femoral artery ligation and intramuscular injection of empty GHM at a dose of 4 ml/kg into the right hind limb, n=8); EPO-GHM group(right femoral artery ligation and intramuscular injection of EPO-GHM at a dose of 5 000 IU/kg into the right hind limb, n=12). The blood flow ratio of ischemic limb (right)/nonischemic limb (left) was measured using a laser Doppler perfusion imager. After 8 weeks, immunohistochemical analysis were used to evaluate the vessel density (vessel density of CD31 positive), arteriole density(vessel density of α-smooth muscle actin(α-SMA) positive) and muscle area(HHF35 positive area). The proliferating index of vessels was evaluated by double immunofluorescent labeling to evaluate effect of EPO-GHM on angiogenesis of ischemia limb. Western blot was used to evaluate the protein expression of EPO receptor, protein kinase B(AKT), p-AKT, endothelial nitric oxide synthase(eNOS), p-eNOS and matrix metalloproteinase 2(MMP-2). (1) Eight weeks later, the blood flow ratio of ischemic limb/nonischemic limb was significantly higher in the EPO-GHM group compared with other groups(0.810±0.080, 0.563±0.051, 0.570±0.056 and 0.561±0.052 respectively, all P0.05). (4)The proliferating index of vessels was higher in the EPO-GHM group compared with other groups(P0.05). RESULTS from present study suggest EPO

  17. A lipid-based liquid crystalline matrix that provides sustained release and enhanced oral bioavailability for a model poorly water soluble drug in rats.

    Science.gov (United States)

    Boyd, Ben J; Khoo, Shui-Mei; Whittaker, Darryl V; Davey, Greg; Porter, Christopher J H

    2007-08-01

    Liquid crystalline phases that are stable in excess water, formed using lipids such as glyceryl monooleate (GMO) and oleyl glycerate (OG), are known to provide a sustained release matrix for poorly water soluble drugs in vitro, yet there has been no report of the use of these materials to impart oral sustained release behaviour in vivo. In the first part of this study, in vitro lipolysis experiments were used to compare the digestibility of GMO with a second structurally related lipid, oleyl glycerate, which was found to be less susceptible to hydrolysis by pancreatic lipase than GMO. Subsequent oral bioavailability studies were conducted in rats, in which a model poorly water soluble drug, cinnarizine (CIN), was administered orally as an aqueous suspension, or as a solution in GMO or OG. In the first bioavailability study, plasma samples were taken over a 30 h period and CIN concentrations determined by HPLC. Plasma CIN concentrations after administration in the GMO formulation were only sustained for a few hours after administration while for the OG formulation, the plasma concentration of cinnarizine was at its highest level 30 h after dosing, and appeared to be increasing. A second study in which CIN was again administered in OG, and plasma samples taken for 120 h, revealed a Tmax for CIN in rats of 36 h and a relative oral bioavailability of 344% when compared to the GMO formulation (117%) and the aqueous suspension formulation (assigned a nominal bioavailability of 100%). The results indicate that lipids that form liquid crystalline structures in excess water, may have application as an oral sustained release delivery system, providing they are not digested rapidly on administration.

  18. Preparation and in vitro-in vivo evaluation of none gastric resident dipyridamole (DIP) sustained-release pellets with enhanced bioavailability.

    Science.gov (United States)

    Xu, Lishuang; Luo, Yanfei; Feng, Jia; Xu, Ming; Tao, Xiaoguang; He, Haibing; Tang, Xing

    2012-01-17

    The objective of this study was to develop none gastric resident sustained-release pellets loaded with dipyridamole with a high bioavailability. Two different kinds of core pellets, one containing citric acid as a pH-modifier (CAP) and, the other without pH-modifier (NCAP) were prepared by extrusion-spheronization and then coated with mixtures of enteric soluble and insoluble polymers (referred to as CAP(1) and NCAP(1)) or insoluble polymer alone (referred to as CAP(2) and NCAP(2)). The relative bioavailability of the sustained-release pellets was studied in fasted beagle dogs after oral administration using a commercially available immediate release tablet (IRT) as a reference. The in vitro release, in vivo absorption and in vitro-in vivo correlation were also evaluated. Results revealed that the plasma drug concentrations after administration of CAP(2), NCAP(1) and NCAP(2) were undetectable, indicating that the drug release was almost zero from the preparations throughout the gastro-intestinal tract. The C(max), T(max) and AUC((0→24)) of CAP(1) were 0.78 ± 0.23 (μg/ml), 3.80 ± 0.30 (h), and 6.74 ± 0.47 (μg/mlh), respectively. While the corresponding values were 2.23 ± 0.32 (μg/ml), 3.00 ± 0.44 (h) and 9.42 ± 0.69 (μg/mlh) for IRT. The relative bioavailability of CAP(1) was 71.55% compared with IRT. By combined incorporation of a pH-modifier into the core of pellets to modify the inner micro-environment and employing mixtures of enteric soluble and insoluble polymers as a retarding layer, drugs with high solubility in stomach and limited solubility in small intestine, such as DIP, could be successfully formulated as sustained release preparations with no pH-dependence in drug release and enhanced bioavailability. Copyright © 2011 Elsevier B.V. All rights reserved.

  19. Solutions as solutions--synthesis and use of a liquid polyester excipient to dissolve lipophilic drugs and formulate sustained-release parenterals.

    Science.gov (United States)

    Asmus, Lutz R; Gurny, Robert; Möller, Michael

    2011-11-01

    Solid poly(lactides) and poly(lactide-co-glycolides) are widely used polymers for sustained-release parenterals. However, they have some unfavorable properties regarding manufacturing of the formulations and administration to the patient due to their solid aggregate state. In contrast, hexyl-substituted poly(lactic acid) (hexPLA, poly(2-hydroxyoctanoic acid)) is a viscous degradable polyester. To date, a two-step ring-opening polymerization was used for its synthesis. Here, we investigated a novel one-pot one-step melt polycondensation method to prepare hexPLA for biomedical applications by a simple green chemistry process. No catalyst or solely pharmaceutically acceptable catalysts and environmentally friendly purification methods without organic solvents were used. The resulting hexPLA polymers are stable under dry heat sterilization conditions. Low molecular weight hexPLAs with less than 5000 g/mol are less viscous than high molecular weight polymers. HexPLA can dissolve lipophilic active substances, with generally high incorporation capacities in low molecular weight polymers. The incorporation of solid compounds increases the viscosity and glass transition temperature, whereas the addition of small amounts of plasticizers or sparse warming significantly decreases the viscosity. Loratadine is soluble in hexPLA up to 28%. This highly concentrated Loratadine-hexPLA formulation released the active compound entirely over 14 days without initial burst in a zero order kinetic, matching the clinical requirements for such a sustained-release formulation. This demonstrates the potential of hexPLA as an excipient for injectable sustained-release formulations. Copyright © 2011 Elsevier B.V. All rights reserved.

  20. Sustained release of diltiazem HCl tableted after co-spray drying and physical mixing with PVAc and PVP.

    Science.gov (United States)

    Al-Zoubi, Nizar; Al-Obaidi, Ghada; Tashtoush, Bassam; Malamataris, Stavros

    2016-01-01

    In this work, aqueous diltiazem HCl and polyvinyl-pyrrolidone (PVP) solutions were mixed with Kollicoat SR 30D and spray dried to microparticles of different drug:excipient ratio and PVP content. Co-spray dried products and physical mixtures of drug, Kollidon SR and PVP were tableted. Spray drying process, co-spray dried products and compressibility/compactability of co-spray dried and physical mixtures, as well as drug release and water uptake of matrix-tablets was evaluated. Simple power equation fitted drug release and water uptake (R(2) > 0.909 and 0.938, respectively) and correlations between them were examined. Co-spray dried products with PVP content lower than in physical mixtures result in slower release, while at equal PVP content (19 and 29% w/w of excipient) in similar release (f2 > 50). Increase of PVP content increases release rate and co-spray drying might be an alternative, when physical mixing is inadequate. Co-spray dried products show better compressibility/compatibility but higher stickiness to the die-wall compared to physical mixtures. SEM observations and comparison of release and swelling showed that distribution of tableted component affects only the swelling, while PVP content for both co-spray dried and physical mixes is major reason for release alterations and an aid for drug release control.

  1. Engineered collagen hydrogels for the sustained release of biomolecules and imaging agents: promoting the growth of human gingival cells.

    Science.gov (United States)

    Choi, Jonghoon; Park, Hoyoung; Kim, Taeho; Jeong, Yoon; Oh, Myoung Hwan; Hyeon, Taeghwan; Gilad, Assaf A; Lee, Kwan Hyi

    2014-01-01

    We present here the in vitro release profiles of either fluorescently labeled biomolecules or computed tomography contrast nanoagents from engineered collagen hydrogels under physiological conditions. The collagen constructs were designed as potential biocompatible inserts into wounded human gingiva. The collagen hydrogels were fabricated under a variety of conditions in order to optimize the release profile of biomolecules and nanoparticles for the desired duration and amount. The collagen constructs containing biomolecules/nanoconstructs were incubated under physiological conditions (ie, 37°C and 5% CO2) for 24 hours, and the release profile was tuned from 20% to 70% of initially loaded materials by varying the gelation conditions of the collagen constructs. The amounts of released biomolecules and nanoparticles were quantified respectively by measuring the intensity of fluorescence and X-ray scattering. The collagen hydrogel we fabricated may serve as an efficient platform for the controlled release of biomolecules and imaging agents in human gingiva to facilitate the regeneration of oral tissues.

  2. In vitro evaluation of sustained released matrix tablets containing ibuprofen: a model poorly water-soluble drug

    Directory of Open Access Journals (Sweden)

    Wendy Leticia Guerra-Ponce

    Full Text Available ABSTRACT A matrix system was developed that releases ibuprofen (IB over a 12-hour period and the influence of the polymer type and concentration on the release rate of the drug was evaluated. Tablets containing different concentrations of Carbopol (CP, hydroxypropyl methylcellulose (HPMC, or ethyl cellulose (EC were prepared using direct compression and the drug content, content uniformity, hardness, friability, dissolution performance, and in vitro release kinetics were examined. Formulated tablets were found to be within acceptable limits for physical and chemical parameters. The release kinetics of the Carbopol(r971P 8% formulation showed the best linearity (r 2 =0.977 in fitting zero-order kinetics, suggesting the release rate was time independent. The drug release from tablets containing 8% CP was extended over approximately 18 hours and the release kinetics were nearly linear, suggesting that this system has the potential to maintain constant plasma drug concentrations over 12 hours, which could reduce the frequency of administration and the occurrence of adverse effects associated with repeated administration of conventional IB tablets.

  3. Constructing herbicide metribuzin sustained-release formulations based on the natural polymer poly-3-hydroxybutyrate as a degradable matrix.

    Science.gov (United States)

    Volova, Tatiana G; Zhila, Natalia O; Vinogradova, Olga N; Nikolaeva, Elena D; Kiselev, Evgeniy G; Shumilova, Anna A; Shershneva, Anna M; Shishatskaya, Ekaterina I

    2016-02-01

    Polymer poly(3-hydroxybutyrate) [P(3HB)] has been used as a matrix in slow-release formulations of the herbicide metribuzin (MET). Physical P(3HB)/MET mixtures in the form of solutions, powders, and emulsions were used to construct different metribuzin formulations (films, granules, pellets, and microparticles). SEM, X-Ray, and DSC proved the stability of these formulations incubated in sterile water in vitro for long periods of time (up to 49 days). Metribuzin release from the polymer matrix has been also studied. By varying the shape of formulations (microparticles, granules, films, and pellets), we were able to control the release time of metribuzin, increasing or decreasing it.

  4. Design of sustained release fine particles using two-step mechanical powder processing: particle shape modification of drug crystals and dry particle coating with polymer nanoparticle agglomerate.

    Science.gov (United States)

    Kondo, Keita; Ito, Natsuki; Niwa, Toshiyuki; Danjo, Kazumi

    2013-09-10

    We attempted to prepare sustained release fine particles using a two-step mechanical powder processing method; particle-shape modification and dry particle coating. First, particle shape of bulk drug was modified by mechanical treatment to yield drug crystals suitable for the coating process. Drug crystals became more rounded with increasing rotation speed, which demonstrates that powerful mechanical stress yields spherical drug crystals with narrow size distribution. This process is the result of destruction, granulation and refinement of drug crystals. Second, the modified drug particles and polymer coating powder were mechanically treated to prepare composite particles. Polymer nanoparticle agglomerate obtained by drying poly(meth)acrylate aqueous dispersion was used as a coating powder. The porous nanoparticle agglomerate has superior coating performance, because it is completely deagglomerated under mechanical stress to form fine fragments that act as guest particles. As a result, spherical drug crystals treated with porous agglomerate were effectively coated by poly(meth)acrylate powder, showing sustained release after curing. From these findings, particle-shape modification of drug crystals and dry particle coating with nanoparticle agglomerate using a mechanical powder processor is expected as an innovative technique for preparing controlled-release coated particles having high drug content and size smaller than 100 μm. Copyright © 2013 Elsevier B.V. All rights reserved.

  5. Formulation development and evaluation of the anti-malaria properties of sustained release artesunate-loaded solid lipid microparticles based on phytolipids.

    Science.gov (United States)

    Chinaeke, E E; Chime, S A; Onyishi, V I; Attama, A A; Okore, V C

    2015-01-01

    CONTEXTS: Artemisinins and its derivatives are considered the basis in the treatment of Plasmodium falciparum malaria due to their high potency and rapid action. However, they have short half life, low solubility, and poor oral bioavailability, hence the need to formulate sustained release lipid particulate dosage form of these drugs. To formulate and evaluate artesunate-loaded solid lipid microparticles (SLMs) based on structured lipid matrices consisting of soybean oil and dika wax. The lipid matrices were characterized by differential scanning calorimetry (DSC), small-angle X-ray diffraction (SAXD), and wide-angle X-ray diffraction (WAXD). The SLMs were prepared by hot melt-homogenization. Time-dependent particle size analysis, time-dependent pH stability studies, encapsulation efficiency (EE%), and in vitro drug release were carried out on the SLMs. In vivo anti-malarial studies were performed using a modified Peter's 4-day suppressive protocol using Plasmodium berghei infected mice. Thermograms of the lipid matrices showed modifications in the microstructure of dika wax as a result of inclusion of soybean oil. SAXD and WAXD diffractograms showed that the lipid matrices were found to be non-lamellar. Particle size of SLM increased with time, while the pH was almost constant. The SLMs had maximum EE% of 80.6% and sustained the release of artesunate more than the reference tablet. In vivo pharmacodynamic studies showed that the SLMs had significant (p daily in the treatment of malaria.

  6. Preparation of a Sustained-Release Nebulized Aerosol of R-terbutaline Hydrochloride Liposome and Evaluation of Its Anti-asthmatic Effects via Pulmonary Delivery in Guinea Pigs.

    Science.gov (United States)

    Li, Qingrui; Zhan, Shuyao; Liu, Qing; Su, Hao; Dai, Xi; Wang, Hai; Beng, Huimin; Tan, Wen

    2018-01-01

    An aerosolized liposome formulation for the pulmonary delivery of an anti-asthmatic medication was developed. Asthma treatment usually requires frequent administration of medication for a sustained bronchodilator response. Liposomes are known for their sustained drug release capability and thus would be a suitable delivery system for prolonging the therapeutic effect of anti-asthmatic medication. Liposomes prepared by thin film hydration were loaded with a model drug, R-terbutaline hydrochloride(R-TBH), using an ammonium sulfate-induced transmembrane electrochemical gradient. This technique provided an encapsulation efficiency of up to 71.35% and yielded R-TBH liposomes with a particle size of approximately 145 ± 20 nm. According to stability studies, these R-TBH liposomes should be stored at 4°C before usage. Compared to R-TBH solution, which showed 90.84% release within 8 h, liposomal R-TBH had a cumulative release of 73.53% at 37°C over 192 h. A next generation impactor (NGI) was used to analyze the particle size distribution in the lungs of R-TBH liposome aerosol in vitro at 5°C. The therapeutic efficacy of the nebulized aerosol of the R-TBH liposomes was assessed via pulmonary delivery in guinea pigs. The results showed that, compared to the R-TBH solution group, the R-TBH liposome group had a prolonged anti-asthma effect.

  7. Tablets compressed with gastric floating pellets coated with acrylic resin for gastro retention and sustained release of famotidine: in-vitro and in-vivo study.

    Science.gov (United States)

    Qi, Xiaole; Jiang, Yingchun; Zhang, Huiting; Wu, Zhenghong

    2015-04-01

    The aim of this study was to prepare a disintegrating gastric floating tablet composed of floating pellets coated with acrylic resin to prolong the gastric residence time and increase the oral bioavailability of famotidine. The gastric floating pellets containing famotidine, stearyl alcohol and microcrystalline cellulose (1 : 10 : 1) were prepared by extrusion-spheronization process and coated with acrylic resin, then compressed into tablets with Avicel PH 301 pellets and cross-linked polyvinylpyrrolidone. The coating weight, volume ratio of Eudragit RL30 D and RS30 D and solid content of coating fluid were optimized by Box-Behnken design. In 0.1 M HCl, tablets can immediately disintegrate into pellets which can remain floating and sustained drug releasing over 12 h. The AUC0-∞ of famotidine gastric floating pellets (7776.52 ± 1065.93 h ng/ml) administered into rats was significantly higher than that of marketed rapid release tablets Xingfading® (Xingyi, Shanghai, China) (4166.23 ± 312.43 h ng/ml), while the relative bioavailability was 187.01 ± 22.81%. The experimental results indicated that the optimized formulation did offer a new gastro retention and sustained release approach to enhance the oral absorption of famotidine. © 2014 Royal Pharmaceutical Society.

  8. Correlation of individual differences in schizotypal personality traits with amphetamine-induced dopamine release in striatal and extrastriatal brain regions.

    Science.gov (United States)

    Woodward, Neil D; Cowan, Ronald L; Park, Sohee; Ansari, M Sib; Baldwin, Ronald M; Li, Rui; Doop, Mikisha; Kessler, Robert M; Zald, David H

    2011-04-01

    Schizotypal personality traits are associated with schizophrenia spectrum disorders, and individuals with schizophrenia spectrum disorders demonstrate increased dopamine transmission in the striatum. The authors sought to determine whether individual differences in normal variation in schizotypal traits are correlated with dopamine transmission in the striatum and in extrastriatal brain regions. Sixty-three healthy volunteers with no history of psychiatric illness completed the Schizotypal Personality Questionnaire and underwent positron emission tomography imaging with [(18)F]fallypride at baseline and after administration of oral d-amphetamine (0.43 mg/kg). Dopamine release, quantified by subtracting each participant's d-amphetamine scan from his or her baseline scan, was correlated with Schizotypal Personality Questionnaire total and factor scores using region-of-interest and voxel-wise analyses. Dopamine release in the striatum was positively correlated with overall schizotypal traits. The association was especially robust in the associative subdivision of the striatum. Voxel-wise analyses identified additional correlations between dopamine release and schizotypal traits in the left middle frontal gyrus and left supramarginal gyrus. Exploratory analyses of Schizotypal Personality Questionnaire factor scores revealed correlations between dopamine release and disorganized schizotypal traits in the striatum, thalamus, medial prefrontal cortex, temporal lobe, insula, and inferior frontal cortex. The association between dopamine signaling and psychosis phenotypes extends to individual differences in normal variation in schizotypal traits and involves dopamine transmission in both striatal and extrastriatal brain regions. Amphetamine-induced dopamine release may be a useful endophenotype for investigating the genetic basis of schizophrenia spectrum disorders.

  9. Thermoplastic polyurethanes for the manufacturing of highly dosed oral sustained release matrices via hot melt extrusion and injection molding.

    Science.gov (United States)

    Claeys, Bart; Vervaeck, Anouk; Hillewaere, Xander K D; Possemiers, Sam; Hansen, Laurent; De Beer, Thomas; Remon, Jean Paul; Vervaet, Chris

    2015-02-01

    This study evaluated thermoplastic polyurethanes (TPUR) as matrix excipients for the production of oral solid dosage forms via hot melt extrusion (HME) in combination with injection molding (IM). We demonstrated that TPURs enable the production of solid dispersions - crystalline API in a crystalline carrier - at an extrusion temperature below the drug melting temperature (Tm) with a drug content up to 65% (wt.%). The release of metoprolol tartrate was controlled over 24h, whereas a complete release of diprophylline was only possible in combination with a drug release modifier: polyethylene glycol 4000 (PEG 4000) or Tween 80. No burst release nor a change in tablet size and geometry was detected for any of the formulations after dissolution testing. The total matrix porosity increased gradually upon drug release. Oral administration of TPUR did not affect the GI ecosystem (pH, bacterial count, short chain fatty acids), monitored via the Simulator of the Human Intestinal Microbial Ecosystem (SHIME). The high drug load (65 wt.%) in combination with (in vitro and in vivo) controlled release capacity of the formulations, is noteworthy in the field of formulations produced via HME/IM. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Evaluation of Ocimum basilicum L. seed mucilage as rate controlling matrix for sustained release of propranolol HCl

    Directory of Open Access Journals (Sweden)

    Majid Saeedi

    2015-01-01

    Full Text Available Polysaccharide mucilage derived from the seeds of Ocimum basilicum L. (family Lamiaceae was investigated for use in matrix formulations containing propranolol hydrochloride. Basil mucilage was extracted and several tablets were formulated. The effect of mucilage on drug release rate was evaluated in comparison with tablets containing two kinds of hydroxypropyl methylcellulose (HPMC K4M and HPMC K100M as standard polymer. The release data were fitted to several models for kinetic evaluation. The results showed that hardness decreased and friability of tablets increased as the concentration of mucilage increased. The rate of release of propranolol HCl from O. basilicm mucilage matrices was mainly controlled by the drug: mucilage ratio. Drug release was slower from the HPMC K4M and HPMCK100M containing tablets compared to the mucilage containing matrices than the drug release from matrices containing O. basilicum seed mucilage in similar ratios.  Formulations containing O. basilicm mucilage were found to exhibit suitable release pattern. The results of kinetic analysis showed that in tablets containing O. basilicm mucilage the highest correlation coefficient was achieved with the zero order model. The swelling and erosion studies revealed that, as the proportion of mucilage in tablets was increased, there was a corresponding increase in percent swelling and a decrease in percent erosion of tablets.

  11. In vivo and in vitro taste masking of ofloxacin and sustained release by forming interpenetrating polymer network beads.

    Science.gov (United States)

    Rajesh, A Michael; Popat, Kiritkumar Mangaldas

    2017-02-01

    Drug-resin complexes (DRCs) of ofloxacin and ion-exchange resins (IERs) were prepared in different ratios of drug/IERs, that is, 1:1, 1:2 and 1:4 (w/w) and investigated for taste masking by in vivo and in vitro release studies. Human volunteers graded AD1:4 (DRC) as tasteless with an average value of 0.3 ± 0.03 and in vitro study showed that AD 1:4 released only 1.70 ± 0.86% of drug at salivary pH within 30s. Fourier transform infrared spectroscopy (FTIR), powder X-ray diffraction (P-XRD) and differential scanning calorimetry (DSC) studies of AD 1:4 showed the change in the morphology of the drug, that is, from crystalline phase to amorphous phase during complex formation. The release of drug from AD 1:4 was completed within 30 min at gastric pH 1.2 and to extend the release time of drug at gastric pH, it was entrapped with different biopolymers, such as sodium alginate (SA) and sodium carboxymethyl cellulose (SCMC), in the presence of ferric chloride and glutaraldehyde (GA) to form interpenetrating polymer network (IPN) beads. FTIR studies revealed that IPN beads were crosslinked with Fe3+ and GA. The release of drug at gastric and intestinal pH was 14.53 ± 1.52% and 65.86 ± 1.29%, respectively, for a contact time of 10 h. The kinetics release study shows fickian diffusion for ionically crosslinked beads and zero-order release for GA crosslinking beads.

  12. Calcium phosphate bone cement containing ABK and PLLA. Sustained release of ABK, the BMD of the femur in rats, and histological examination

    Energy Technology Data Exchange (ETDEWEB)

    Kusaka, T.; Tanaka, A.; Sasaki, S.; Takano, I.; Tahara, Y.; Ishii, Y. [Kyorin Univ., Tokyo (Japan). Dept. of Orhtopaedic Surgery

    2001-07-01

    Bone cement was prepared by mixing CPC95 (Mitsubishi Material Co., Ltd.), ABK, and PLLA at a ratio of 14 : 1 : 2. In vitro, Antibiotic sustained release tests were performed by the total amount exchange method. In animal experiments, the bone cement was infused into the right femur of 18-month-old female SD rats. After 1, 2, 4, or 6 months, the BMD was determined by DXA in the bilateral femoral bones. In addition, hard tissue specimens were prepared, and the state of bone formation was observed. The release of the antibiotic was 1.73 {mu}g/ml until 18 days after administration, maintaining a concentration over the MIC80 for MRSA. In the animal experiments, the BMD significantly increased after 2 - 4 months. In the hard tissue specimens, direct binding on the bone-cement interface and bone formation in the cement were observed after 1 month. (orig.)

  13. A multicenter, randomized, double-blind, placebo-controlled, 6-month trial of bupropion hydrochloride sustained-release tablets as an aid to smoking cessation in hospital employees

    DEFF Research Database (Denmark)

    Dalsgareth, Oli Jacob; Hansen, Niels-Christian Gerner; Søes-Petersen, Ulrik

    2004-01-01

    Despite changes in smoking behavior, one-third of the Danish population continues to smoke. Many of these smokers are hospital employees. This 6-month, multicenter, parallel group, randomized, double-blind, placebo-controlled study evaluated treatment with bupropion hydrochloride sustained release...... (Zyban) compared with placebo as an aid to smoking cessation in health care workers. A total of 336 hospital employees who smoked at least 10 cigarettes daily were randomized (2:1) to 7 weeks of treatment with bupropion (n=222) or placebo (n=114). All participants were motivated to quit smoking......% in the bupropion group and 18% in the placebo group, p

  14. Bioavailability and pharmacokinetic properties of 2 sustained-release formulations of diclofenac sodium, Voltaren vs inflaban: effect of food on inflaban bioavailability.

    Science.gov (United States)

    Zmeili, S; Hasan, M; Najib, N; Sallam, E; Deleq, S; Shubair, M

    1996-12-01

    In this study, in vitro characterization, bioavailability and pharmacokinetics of 2 different sustained-release diclofenac sodium dosage forms were compared, Voltaren (100 mg tablets), manufactured by Ciba-Geigy and Inflaban (100 mg enteric-coated tablets), manufactured by the Arab Pharmaceutical Manufacturing Company. The in vitro results demonstrated a faster rate of dissolution for Inflaban as compared to Voltaren, but both products exhibited a sustained-release pattern. The bioavailability study was conducted on 20 healthy male subjects who received a single oral dose (100 mg) of each product according to a randomized 2-way crossover design. Blood samples were obtained over a 26-hour period, and drug concentrations were determined by an HPLC method. Concentration time profiles revealed a sustained-release pattern for both products. The Tlag for Voltaren was 0.8 +/- 0.2 h, significantly shorter than for Inflaban (1.7 +/- 0.2 h) indicating a faster rate of absorption from the upper gastrointestinal tract. The Cmax obtained with Voltaren was significantly higher than that obtained with Inflaban (1,161 +/- 102 and 799 +/- 83, respectively). With respect to Tmax and AUC0-26h parameters, both products were not found to be statistically different. Tmax for Voltaren and Inflaban was 4.2 +/- 0.5 and 4.5 +/- 0.4 h, respectively, whereas AUC0-26h values for both products were 5,423 +/- 562 and 5,237 +/- 520 ng x h/ml, respectively. It is believed that the observed differences between Voltaren and Inflaban are mainly due to the fact that Inflaban is designed as an enteric-coated tablet form, with a core tablet having different sustained-release behavior. In addition, the effect of food on the bioavailability of Inflaban was evaluated in randomly selected 6 male volunteers. Our results revealed that, following light and heavy meals, the AUC0-30 and Cmax were minimally affected by food whereas a significant increase in Tmax and Tlag as compared to fasting conditions was

  15. Polymeric emulsion and crosslink-mediated synthesis of super-stable nanoparticles as sustained-release anti-tuberculosis drug carriers.

    Science.gov (United States)

    Choonara, Yahya E; Pillay, Viness; Ndesendo, Valence M K; du Toit, Lisa C; Kumar, Pradeep; Khan, Riaz A; Murphy, Caragh S; Jarvis, Debbie-Leigh

    2011-10-15

    This study focused on evaluating four emulsion-based processing strategies for polymeric nanoparticle synthesis to explicate the mechanisms of nanoparticle formation and the influence on achieving sustained-release of two anti-tuberculosis drugs, isoniazid and rifampicin. Poly(lactic-co-glycolic acid) (PLGA) nanoparticles were formulated with and without sorbitan mono-oleate as a stabilizer using emulsion-solvent-surfactant-evaporation (ESSE) and emulsion-solvent-evaporation (ESE) approaches. An alginate solution gelled by ionic crosslinking with calcium chloride was employed to prepare alginate hydrogel nanoparticles via reverse-emulsion-cationic-gelification (RECG) and reverse-emulsion-surfactant-cationic-gelification (RESCG) approaches. In vitro drug release analysis was performed. The size, zeta potential and morphology of the nanoparticles were analyzed. Molecular mechanics energy relationships (MMER) were employed to explore the spatial disposition of alginate and PLGA with respect to the emulsifying profile of sorbitan monooleate and to corroborate the experimental findings. Results revealed that particle size of the PLGA nanoparticles was influenced by the stabilizer concentration. Nanoparticles synthesized by the ESSE approach had smaller sizes of 240±8.7 nm and 195.5±5.4 nm for rifampicin- and isoniazid-loaded nanoparticles, respectively. This was a substantial size reduction from nanoparticles generated by the ESE approach (>1000 nm). The RESCG approach produced stable and higher nanoparticle yields with desirable size (277±1.0 nm; 289±1.2 nm), a low polydispersity index (27.1±0.3 mV; 28.5±0.5 mV) and drug entrapment efficiency of 73% and 75% for isoniazid and rifampicin, respectively. Drug release from the ESSE and RESCG synthesized nanoparticles displayed desirable release of the two anti-TB drugs with sustained zero-order kinetics over a period of 8h. MMER supported the mechanisms of nanoparticle formation with a sphericalized interlaced network

  16. PEGylated TNF-related apoptosis-inducing ligand (TRAIL)-loaded sustained release PLGA microspheres for enhanced stability and antitumor activity.

    Science.gov (United States)

    Kim, Tae Hyung; Jiang, Hai Hua; Park, Chan Woong; Youn, Yu Seok; Lee, Seulki; Chen, Xiaoyuan; Lee, Kang Choon

    2011-02-28

    The purpose of this work was to develop an effective PEGylated TNF-related apoptosis-inducing ligand (PEG-TRAIL) delivery system for antitumor therapy based on local injection to tumor sites that has a sustained effect without protein aggregation or an initial release burst. The authors designed poly (lactic-co-glycolic) acid (PLGA) microspheres that deliver PEG-TRAIL locally and continuously at tumor sites with sustained biological activity and compared its performance with that of TRAIL microspheres. TRAIL or PEG-TRAIL was microencapsulated into PLGA microspheres using a double-emulsion solvent extraction method. Prepared TRAIL and PEG-TRAIL microspheres showed entirely spherical, smooth surfaces. However, PEG-TRAIL microspheres exhibited a 2.07-fold higher encapsulation efficiency than TRAIL microspheres, and exhibited a tri-phasic in vitro release profile with a lower initial burst (15.8%) than TRAIL microspheres (42.7%). Furthermore, released PEG-TRAIL showed a continued ability to induce apoptosis over 14 days. In vivo pharmacokinetic studies also demonstrated that PEG-TRAIL microspheres had a sustained release profile (18 days), and that the steady-state concentration of PEG-TRAIL in rat plasma was reached at day 3 and maintained until day 15; its steady-state concentration in rat plasma changed from 1444.3 ± 338.4 to 2697.7 ± 419.7 pg/ml. However, TRAIL microspheres were released out within 2 days after administration. Finally, in vivo antitumor tests revealed that tumor growths were significantly more inhibited by a single dose of PEG-TRAIL microspheres than TRAIL microspheres when delivered at 300 μg of TRAIL/mouse. Tumors taken from mouse treated with PEG-TRAIL microspheres showed 78.3% tumor suppression at 24 days, and this was 3.02-fold higher than that observed for TRAIL microspheres (25.9% tumor inhibition). Furthermore, these improved pharmaceutical characteristics of PEG-TRAIL microspheres resulted in superior therapeutic effects without

  17. Investigation of the potential application of sodium bentonite as an excipient in formulation of sustained release tablets

    Directory of Open Access Journals (Sweden)

    Jamal Alyoussef Alkrad

    2017-05-01

    Full Text Available In this study, the application of sodium bentonite (SB in formulation of tablets prepared by direct compression for oral administration was tested. Three different model drugs with different solubilities: paracetamol, diclofenac sodium and metformin HCl were tested. Each drug was mixed with SB at ratio of 50% and the mixtures were subsequently compressed. Compatibility studies were conducted using both Deferential Scanning Calorimeter (DSC and Fourier Transform Infrared Spectroscopy (FTIR. The dissolution profile for each drug was determined in USP-buffers at different time intervals. Diclofenac sodium in pH 6.8 buffer and paracetamol in both pH 6.8 and pH 4.5 buffers showed extended release. However, metformin HCl showed immediate release at the different pH values. The study showed that using SB was possible to prepare tablets with different release profiles. However, these profiles differ depending on dissolution media and drug type.

  18. Self-assembled nanoparticles of modified-chitosan conjugates for the sustained release of dl-α-tocopherol

    DEFF Research Database (Denmark)

    Quinones, Javier Perez; Gothelf, Kurt Vesterager; Kjems, Jørgen

    2013-01-01

    Synthetic O6-succinylated chitosan and commercial glycol chitosan were covalently linked to dl-α-tocopheryl monoesters for controlled release of vitamin E. These conjugates formed self-assembled nanoparticles in aqueous solution with 254–496 nm mean diameters and dl-α-tocopherol contents between ...

  19. Characterization of extracellular polymeric substance (EPS) fractions produced by Microcystis aeruginosa under the stress of linoleic acid sustained-release microspheres.

    Science.gov (United States)

    Ni, Lixiao; Li, Danye; Rong, Shiyi; Su, Lili; Zhou, Wei; Wang, Peifang; Wang, Chao; Li, Shiyin; Acharya, Kumud

    2017-07-20

    This paper focuses on the characterization of extracellular polymeric substances (EPS), which are composed of soluble EPS (SL-EPS), loosely bound EPS (LB-EPS), and tightly bound EPS (TB-EPS) produced by Microcystis aeruginosa under the stress of linoleic acid (LA) and LA sustained-release microspheres. Three-dimensional excitation-emission matrix (3D-EEM) fluorescence spectroscopy and Fourier transform infrared (FTIR) spectrometry were used to characterize three forms of EPS while the content of polysaccharide and protein was tested, respectively. The results showed that the highest inhibitor rate (IR) occurred when M. aeruginosa were exposed to LA sustained-release microspheres of 0.3 g L(-1). The 3D-EEM contour demonstrated that tryptophan and protein-like substances were detected in all three EPS fractions, whereas humic acid-like substance was only distributed in SL-EPS, and aromatic proteins merely existed in LB-EPS and TB-EPS. The infrared spectrum showed that functional groups in three EPS fractions had no obvious change in all experimental groups. Polysaccharide (1120-1270 cm(-1), C-O-C and C-O stretching vibration) and protein (1384-1670 cm(-1), C-N and N-H stretching) were detected in three forms of EPS. Graphical abstract ᅟ.

  20. Primary care treatment of depression in the elderly: a double-blind, multi-centre study of flupenthixol ('Fluanxol') and sustained-release amitriptyline.

    Science.gov (United States)

    Høstmaelingen, H J; Asskilt, O; Austad, S G; Fjellheim, J; Høstmaelingen, E A; Kristiansen, P H; Olsen, T I; Skotte, T; Ofsti, E

    1989-01-01

    A multi-centre general practice study was carried out to compare flupenthixol and a sustained-release preparation of amitriptyline in the primary care treatment of depression in the elderly. Fifty-one clinically depressed patients, aged 65 years or over, were allocated at random to one of the two treatment groups in this 4-week double-blind, double-dummy study. On entry, patients received either a 0.5 mg flupenthixol tablet in the morning and a placebo capsule at night (25 patients) or a 25 mg sustained-release amitriptyline capsule at night and a placebo tablet in the morning (26 patients), but at the end of the first or second weeks the dosage could be doubled according to the assessed clinical need. Fourteen patients in each treatment group had their dosages doubled. Patient assessment was undertaken on study entry and after 1, 2 and 4 weeks of treatment using a 0 to 3 scale global assessment and the Montgomery Asberg Depression Rating Scale; side-effects were recorded on the UKU Scale. After 4-weeks' treatment, over 80% of patients in each group had improved and in the flupenthixol group there was additionally a noticeable and highly significant reduction in symptom severity after only 1 week of treatment. Patients treated with flupenthixol had fewer and milder side-effects.

  1. Gallium-Loaded Dissolvable Microfilm Constructs that Provide Sustained Release of Ga(3+) for Management of Biofilms.

    Science.gov (United States)

    Herron, Maggie; Schurr, Michael J; Murphy, Christopher J; McAnulty, Jonathan F; Czuprynski, Charles J; Abbott, Nicholas L

    2015-12-30

    The persistence of bacterial biofilms in chronic wounds delays wound healing. Although Ga(3+) can inhibit or kill biofilms, precipitation as Ga(OH)3 has prevented its use as a topical wound treatment. The design of a microfilm construct comprising a polyelectrolyte film that releases noncytotoxic concentrations of Ga(3+) over 20 d and a dissolvable micrometer-thick film of polyvinylalcohol that enables facile transfer onto biomedically important surfaces is reported. By using infrared spectroscopy, it is shown that the density of free carboxylate/carboxylic acid and amine groups within the polyelectrolyte film regulates the capacity of the construct to be loaded with Ga(3+) and that the density of covalent cross-links introduced into the polyelectrolyte film (amide-bonds) controls the release rate of Ga(3+) . Following transfer onto the wound-contact surface of a biologic wound dressing, an optimized construct is demonstrated to release ≈0.7 μg cm(-2) d(-1) of Ga(3+) over 3 weeks, thus continuously replacing Ga(3+) lost to precipitation. The optimized construct inhibits formation of P. aeruginosa (two strains; ATCC 27853 and PA01) biofilms for up to 4 d and causes pre-existing biofilms to disperse. Overall, this study provides designs of polymeric constructs that permit facile modification of the wound-contacting surfaces of dressings and biomaterials to manage biofilms. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Design and release characteristics of sustained release tablet containing metformin HCl Planejamento e características de liberação de comprimidos de liberação controlada de cloridrato de metformina

    Directory of Open Access Journals (Sweden)

    Subal Chandra Basak

    2008-09-01

    Full Text Available Metformin hydrochloride (metformin HCl was formulated as a hydrophobic matrix sustained release tablet employing wax materials and the sustained release behavior of the fabricated tablet was investigated. Sustained release matrix tablets containing 500 mg metformin HCl were developed using different bees wax combinations. The tablets were prepared by wet granulation technique. The formulation was optimized on the basis of acceptable tablet properties and in vitro drug release. The resulting formulation produced monolithic tablets with optimum hardness, uniform thickness, consistent weight uniformity and low friability. Statistically significant differences were found among the drug release profile from different bees wax combination matrices. The results of dissolution studies indicated that formulations F-III, F-IV and F-V (bees wax and cetyl alcohol combination matrices, exhibited drug release pattern very close to theoretical release profile. Applying kinetic equation models, the mechanism of release of the drug from the three formulations was found to be followed Higuchi model, as the plots showed high linearity, with correlation coefficient (R² value of 0.98 or more. Tablet matrices containing cetyl alcohol gave better release of the drug than other materials studied. However, the rate of release varied with amount of cetyl alcohol in the matrix. The 'n' value lies below 0.5 (Korsmeyer-Peppas model demonstrating that the mechanism controlling the drug release was the quasi Fickian. Therefore, the results of the kinetic study obtained permit us to conclude that the fabricated hydrophobic matrix tablets, in this case, delivers the drug through diffusion dominated mechanism.O cloridrato de metformina (metformina.HCl foi formulado como comprimido de liberação controlada, empregando materiais cerosos como matriz hidrofóbica, e o comportamento dessa formulação foi investigado. Comprimidos com matriz de liberação controlada contendo 500 mg

  3. Nanoencapsulation of Nimodipine in Novel Biocompatible Poly(propylene-co-butylene succinate Aliphatic Copolyesters for Sustained Release

    Directory of Open Access Journals (Sweden)

    Sofia Papadimitriou

    2009-01-01

    Full Text Available Biocompatible poly(propylene-co-butylene succinate (PPBSu copolyesters, containing up to 50 mol% butylene succinate units, were synthesized by the two-stage melt polycondensation method (esterification and polycondensation. The copolymers were fully characterized and biocompatibility studies were also performed. They were proved to be biocompatible and they were used as polymer matrices for the preparation of drug loaded nanoparticles. Nimodipine was selected as a model hydrophobic poorly water soluble drug. From the results obtained by dynamic light scattering (DLS and scanning electron microscopy (SEM, drug loaded copolymer nanoparticles were found to exhibit a spherical shape and their mean diameter appeared in the range of 180–200 nm. Fourier Transformation-Infrared Spectroscopy (FTIR spectra indicated that no chemical interaction between the drug and the matrix could be justified, while Wide-Angle X-Ray Diffraction (WAXD patterns proved a low degree of crystallinity of Nimodipine in the nanoparticles. The release behavior of the model drug from nanoparticles was also investigated in order to identify modifications and find out any possible correlation between the chemical composition of the polymer matrix and the drug release rates.

  4. Evaluation of carbopol-methyl cellulose based sustained-release ocular delivery system for pefloxacin mesylate using rabbit eye model.

    Science.gov (United States)

    Sultana, Yasmin; Aqil, M; Ali, Asgar; Zafar, Shadaab

    2006-01-01

    The major purpose of this study was to develop and characterize a series of carbopol- and methyl cellulose-based solutions as the in situ gelling vehicles for ophthalmic drug delivery. The rheological properties, in vitro release as well as in vivo pharmacological response of a combination of polymer solutions, including carbopol and methyl cellulose, were evaluated. It was found that the optimum concentration of carbopol solution for the in situ gel-forming delivery systems was 0.3% (w/w), and that for methyl cellulose solution was 1.5% (w/w). The mixture of 0.3% carbopol and 1.5% methyl cellulose solutions showed a significant enhancement in gel strength in the physiological condition; this gel mixture was also found to be free flowing at pH 4.0 and 25 degrees C. The rheological behaviors of carbopol/methyl cellulose solution were not affected by the incorporation of the drug. Drug levels in the aqueous humor of the rabbits were well above the MIC-values of relevant bacteria after 12 hours, the results of an optimized formulation containing 0.18% of pefloxacin mesylate compared well with the 0.3% marketed eye drop formulation, indicating our formulation to be significantly better considering that a similar effect was obtained at half the concentration. Both the in vitro release and in vivo pharmacological studies indicated that the carbopol/methyl cellulose solution had better ability to retain drug than did the carbopol or methyl cellulose solutions alone. The results demonstrated that the carbopol/methyl cellulose mixture can be used as an in situ gelling vehicle to enhance the ocular bioavailability of pefloxacin mesylate.

  5. Organic Nanovesicular Cargoes for Sustained Drug Delivery: Synthesis, Vesicle Formation, Controlling “Pearling” States, and Terfenadine Loading/Release Studies

    Directory of Open Access Journals (Sweden)

    Ajay Kumar Botcha

    2014-01-01

    Full Text Available “Sustained drug delivery systems” which are designed to accomplish long-lasting therapeutic effect are one of the challenging topics in the area of nanomedicine. We developed an innovative strategy to prepare nontoxic and polymer stabilized organic nanovesicles (diameter: 200 nm from a novel bolaamphiphile, where two hydrogen bonding acetyl cytosine molecules connected to 4,4′′-positions of the 2,6-bispyrazolylpyridine through two flexible octyne chains. The nanovesicles behave like biological membrane by spontaneously self-assembling into “pearl-like” chains and subsequently forming long nanotubes (diameter: 150 nm, which further develop into various types of network-junctions through self-organization. For drug loading and delivery applications, the nanovesicles were externally protected with biocompatible poly(ethyleneglycol-2000 to prevent them from fusion and ensuing tube formation. Nontoxic nature of the nanovesicles was demonstrated by zebrafish teratogenicity assay. Biocompatible nanovesicles were loaded with “terfenadine” drug and successfully utilized to transport and release drug in sustained manner (up to 72 h in zebrafish larvae, which is recognized as an emerging in vivo model system.

  6. Efficient Encapsulation and Sustained Release of Basic Fibroblast Growth Factor in Nanofilm: Extension of the Feeding Cycle of Human Induced Pluripotent Stem Cell Culture.

    Science.gov (United States)

    Han, Uiyoung; Park, Hee Ho; Kim, Yu Jin; Park, Tai Hyun; Park, Ju Hyun; Hong, Jinkee

    2017-08-02

    Basic fibroblast growth factor (bFGF) has an established pivotal function in biomedical engineering, especially for the human pluripotent stem cells (iPSCs). However, the limitation of bFGF is the ease of denaturation under normal physiological conditions, inducing loss of its activity. In this study, we designed multi-trilayered nanofilm composed of a repeating polycation/polyanion/bFGF structure, which has high loading efficiency and short buildup time. We also investigated that the loading and release of bFGF from the nanofilm with two parameters (counter-polyanion and film architectures). Then, we prepared the optimized nanofilm which maintains a sustained bFGF level in physiological condition to apply the nanofilm to human iPSCs culture. The amount of bFGF release from 12 trilayer nanofilm was 36.4 ng/cm(2), and activity of bFGF encapsulated into the nanofilm was maintained (60%) until 72 h during incubation at 37 °C. As a result, the iPSCs grown in the presence of the nanofilm with tridaily replacement of growth medium maintained undifferentiated morphology and expression levels of pluripotency marker proteins.

  7. The effect of egg albumin on the crystalline properties of carbamazepine in sustained release hydrophilic matrix tablets and in aqueous solutions.

    Science.gov (United States)

    Katzhendler, I; Azoury, R; Friedman, M

    2000-04-03

    The influence of egg albumin (EA) on the crystal habit properties of carbamazepine (CBZ) in aqueous solutions, solid-state, and in sustained release matrix tablets was investigated using differential scanning calorimetry (DSC), hot-stage microscopy (HSM), X-ray powder diffraction (XRD), scanning electron microscopy (SEM) and contact angle goniometer (CAG). The results suggest that in solid-state mixtures, EA affected the polymorphic transitions of CBZ from the beta to the alpha form. In hydrated matrix tablets and aqueous solutions, EA influenced the conversion rate of CBZ to the dihydrate form depending on EA concentration. It was found that increasing EA concentration enhanced CBZ dihydrate aggregation, an effect that leads to the formation of crystals with high mechanical strength and decrease of CBZ solubility. Possible mechanisms, which explain crystal growth and aggregation, as well as alteration of CBZ polymorphic transitions in the solid-state, gel layer, and in aqueous solution were suggested. In the gel layer of hydrated tablets the kinetics of CBZ transformation to the dihydrate form, crystal growth and aggregation were influenced by various processes: matrix hydration, erosion mechanism and the formation of metastable conditions, which favor aggregation and growth. The release kinetics of CBZ from the matrix highly correlated with the crystalline and morphological changes occurring in the matrix.

  8. Coaxial Electrospinning with Mixed Solvents: From Flat to Round Eudragit L100 Nanofibers for Better Colon-Targeted Sustained Drug Release Profiles

    Directory of Open Access Journals (Sweden)

    Deng-Guang Yu

    2014-01-01

    Full Text Available A modified coaxial electrospinning process was developed for creating drug-loaded composite nanofibers. Using a mixed solvent of ethanol and N,N-dimethylacetamide as a sheath fluid, the electrospinning of a codissolving solution of diclofenac sodium (DS and Eudragit L100 (EL100 could run smoothly and continuously without any clogging. A series of analyses were undertaken to characterize the resultant nanofibers from both the modified coaxial process and a one-fluid electrospinning in terms of their morphology, physical form of the components, and their functional performance. Compared with those from the one-fluid electrospinning, the DS-loaded EL100 fibers from the modified coaxial process were rounder and smoother and possessed higher quality in terms of diameter and distribution with the DS existing in the EL100 matrix in an amorphous state; they also provided a better colon-targeted sustained drug release profile with a longer release time period. The modified coaxial process not only can smooth the electrospinning process to prevent clogging of spinneret, but also is a useful tool to tailor the shape of electrospun nanofibers and thus endow them improved functions.

  9. Use of rotary fluidized-bed technology for development of sustained-release plant extracts pellets: potential application for feed additive delivery.

    Science.gov (United States)

    Meunier, J-P; Cardot, J-M; Gauthier, P; Beyssac, E; Alric, M

    2006-07-01

    The aim of this study was to develop sustained release plant extracts as a potential alternative to antibiotic growth promoters for growing pigs. Pellets with a core based on microcrystalline cellulose and 3 active compounds (eugenol, carvacrol, and thymol) were prepared using rotary fluidized-bed technology. Two particle sizes were produced that had a mean size of approximately 250 and 500 mum. Results show the process was able to produce pellets with a spherical and homogenous form when 10% of the active compounds were incorporated into the core. When active compounds were increased to 20%, the pellet became stickier, and the yield decreased from 90 to 65%. Different amounts of coating in the form of an aqueous-based ethylcellulose (EC) dispersion (Surelease) were applied to the core to modify the release of active compounds. The efficacy of the coating was evaluated in vitro using a flow-through cell apparatus. The time to achieve 50 and 90% dissolution increased with the increase in particle size (P eugenol was always faster than for thymol or carvacrol. The close monitoring of plant extract behavior in the gastrointestinal tract could become a key factor in the continued use of phyto-molecules as alternatives to antibiotic growth promoters and in optimizing the balance between cost and efficacy. Different microencapsulation technologies can be used, of which the rotary fluidized bed warrants consideration because of the quality of the products obtained.

  10. Low Molecular Weight Glucosamine/L-lactide Copolymers as Potential Carriers for the Development of a Sustained Rifampicin Release System: Mycobacterium Smegmatis as a Tuberculosis Model

    Science.gov (United States)

    Ragusa, Jorge Alejandro

    suggest that these drug carrier materials are potentially very attractive candidates for the development of high-payload, sustained-release antibiotic/resorbable polymer particle systems for treating bacterial lung infections.

  11. Trehalose maintains bioactivity and promotes sustained release of BMP-2 from lyophilized CDHA scaffolds for enhanced osteogenesis in vitro and in vivo.

    Directory of Open Access Journals (Sweden)

    Jun Zhao

    Full Text Available Calcium phosphate (Ca-P scaffolds have been widely employed as a supportive matrix and delivery system for bone tissue engineering. Previous studies using osteoinductive growth factors loaded Ca-P scaffolds via passive adsorption often experience issues associated with easy inactivation and uncontrolled release. In present study, a new delivery system was fabricated using bone morphogenetic protein-2 (BMP-2 loaded calcium-deficient hydroxyapatite (CDHA scaffold by lyophilization with addition of trehalose. The in vitro osteogenesis effects of this formulation were compared with lyophilized BMP-2/CDHA construct without trehalose and absorbed BMP-2/CDHA constructs with or without trehalose. The release characteristics and alkaline phosphatase (ALP activity analyses showed that addition of trehalose could sufficiently protect BMP-2 bioactivity during lyophilization and achieve sustained BMP-2 release from lyophilized CDHA construct in vitro and in vivo. However, absorbed BMP-2/CDHA constructs with or without trehalose showed similar BMP-2 bioactivity and presented a burst release. Quantitative real-time PCR (RT-qPCR and enzyme-linked immunosorbent assay (ELISA demonstrated that lyophilized BMP-2/CDHA construct with trehalose (lyo-tre-BMP-2 promoted osteogenic differentiation of bone marrow stromal cells (bMSCs significantly and this formulation could preserve over 70% protein bioactivity after 5 weeks storage at 25°C. Micro-computed tomography, histological and fluorescent labeling analyses further demonstrated that lyo-tre-BMP-2 formulation combined with bMSCs led to the most percentage of new bone volume (38.79% ± 5.32% and area (40.71% ± 7.14% as well as the most percentage of fluorochrome stained bone area (alizarin red S: 2.64% ± 0.44%, calcein: 6.08% ± 1.37% and mineral apposition rate (4.13 ± 0.62 µm/day in critical-sized rat cranial defects healing. Biomechanical tests also indicated the maximum stiffness (118.17 ± 15.02 Mpa and

  12. Slow and sustained nitric oxide releasing compounds inhibit multipotent vascular stem cell proliferation and differentiation without causing cell death

    Energy Technology Data Exchange (ETDEWEB)

    Curtis, Brandon M.; Leix, Kyle Alexander [Department of Chemistry, Central Michigan University, Mount Pleasant, MI 48859 (United States); Ji, Yajing [Department of Biomedical Science and Medicine, Michigan State University, East Lansing, MI 48824 (United States); Glaves, Richard Samuel Elliot [Department of Biology, Central Michigan University, Mount Pleasant, MI 48859 (United States); Ash, David E. [Department of Chemistry, Central Michigan University, Mount Pleasant, MI 48859 (United States); Mohanty, Dillip K., E-mail: Mohan1dk@cmich.edu [Department of Chemistry, Central Michigan University, Mount Pleasant, MI 48859 (United States)

    2014-07-18

    Highlights: • Multipotent vascular stem cells (MVSCs) proliferate and differentiate. • Nitric oxide inhibits proliferation of MVSCs. • Nitric oxide inhibits MVSC differentiation to mesenchymal-like stem cells (MSCs). • Smooth muscle cells (SMCs) neither de-differentiate nor proliferate. - Abstract: Atherosclerosis is the leading cause of cerebral and myocardial infarction. It is believed that neointimal growth common in the later stages of atherosclerosis is a result of vascular smooth muscle cell (SMC) de-differentiation in response to endothelial injury. However, the claims of the SMC de-differentiation theory have not been substantiated by monitoring the fate of mature SMCs in response to such injuries. A recent study suggests that atherosclerosis is a consequence of multipotent vascular stem cell (MVSC) differentiation. Nitric oxide (NO) is a well-known mediator against atherosclerosis, in part because of its inhibitory effect on SMC proliferation. Using three different NO-donors, we have investigated the effects of NO on MVSC proliferation. Results indicate that NO inhibits MVSC proliferation in a concentration dependent manner. A slow and sustained delivery of NO proved to inhibit proliferation without causing cell death. On the other hand, larger, single-burst NO concentrations, inhibits proliferation, with concurrent significant cell death. Furthermore, our results indicate that endogenously produced NO inhibits MVSC differentiation to mesenchymal-like stem cells (MSCs) and subsequently to SMC as well.

  13. [Solubilizing and sustained-releasing abilities and safety preliminary evaluation for paclitaxel based on N-octyl-O, N-carboxymethyl chitosan polymeric micelles].

    Science.gov (United States)

    Huo, Mei-Rong; Zhang, Yong; Zhou, Jian-Ping; Lü, Lin; Liu, Huan; Liu, Fang-Jie

    2008-08-01

    A series of novel self-assembled polymeric micelles based on carboxymethyl chitosan bearing long chain alkyl chains (N-octyl-O, N-carboxymethyl chitosan, OCC) was synthesized. PTX loaded OCC polymeric micelles (PTX-OCC) were prepared by dialysis method. The effects of the degree of substitutions (DS) of octyl groups on the solubilizing abilities of OCC for paclitaxel were studied. The PTX-OCC were characterized using drug loading content, drug encapsulation efficiency, dynamic light scattering, zeta potential and transmission electron microscopy (TEM). Take PTX injection (PTX-INJ) as control, the safety of PTX-OCC including hemolysis, hypersensitiveness in guinea pigs and acute toxicity in mice were also evaluated. OCC showed excellent loading capacities for paclitaxel with the DS of octyl groups in the range of 37.9% - 58.6%. Drug loading contents were up to 24.9% - 34.4% with drug encapsulation efficiency 56.3% - 89.3%, which both increased with the increasing of DS of octyl groups. The mean size of PTX-OCC was 186.4 - 201.1 nm which decreased with the increasing of DS of octyl groups. The zeta potential was -47.5 to -50.9 mV, which had no obvious relation with the DS of octyl groups. The TEM images showed a spherical shape. No burst release phenomena were observed and drug cumulative release was in the range of 60% -95% in 15 days. PTX-OCC with higher DS of octyl groups showed stronger sustained releasing ability. In terms of the induction of membrane damage and hypersensitiveness, PTX-OCC was superior to PTX-INJ. The LD50 and its 95% confidence interval of PTX-OCC were 134.4 (125.0 - 144.6) mg x kg(-1), which was 2.7 fold of PTX-INJ. The present PTX-OCC could be potentially useful as safety carriers for intravenous delivery.

  14. Octadecylamine-Mediated Versatile Coating of CoFe2O4 NPs for the Sustained Release of Anti-Inflammatory Drug Naproxen and in Vivo Target Selectivity.

    Science.gov (United States)

    Georgiadou, Violetta; Makris, George; Papagiannopoulou, Dionysia; Vourlias, Georgios; Dendrinou-Samara, Catherine

    2016-04-13

    Magnetic nanoparticles (MNPs) can play a distinct role in magnetic drug delivery via their distribution to the targeted area. The preparation of such MNPs is a challenging multiplex task that requires the optimization of size, magnetic, and surface properties for the achievement of desirable target selectivity, along with the sustained drug release as a prerequisite. In that context, CoFe2O4 MNPs with a small size of ∼7 nm and moderate saturation magnetization of ∼60 emu g(-1) were solvothermally synthesized in the presence of octadecylamine (ODA) with a view to investigate the functionalization route effect on the drug release. Synthetic regulations allowed us to prepare MNPs with aminated (AmMNPs) and amine-free (FAmMNPs) surface. The addition of the nonsteroidal anti-inflammatory drug with a carboxylate donor, Naproxen (NAP), was achieved by direct coupling with the NH2 groups, rendered by ODA, through the formation of an amide bond in the case of AmMNPs. In the case of FAmMNPs, indirect coupling of NAP was performed through an intermediate linker (polyethylenimine) and on PEG-ylated MNPs. FT-IR, (1)H NMR, (13)C NMR, and UV-vis data confirmed the addition of NAP, whereas diverse drug-release behavior was observed for the different functionalization approaches. The biological behavior of the MNPs@NAP was evaluated in vitro in rat serum and in vivo in mice, after radiolabeling with a γ-emitting radionuclide, (99m)Tc. The in vivo fate of MNPs@NAP carriers was in straightforward relation with the direct or indirect coupling of NAP. Furthermore, an inflammation was induced intramuscularly, where the directly coupled (99m)Tc-MNPs@NAP carriers showed increased accumulation at the inflammation site.

  15. Computational studies on self-assembled paclitaxel structures: templates for hierarchical block copolymer assemblies and sustained drug release.

    Science.gov (United States)

    Guo, Xin D; Tan, Jeremy P K; Kim, Sung H; Zhang, Li J; Zhang, Ying; Hedrick, James L; Yang, Yi Y; Qian, Yu

    2009-11-01

    Paclitaxel-loaded poly(ethylene oxide)-b-poly(lactide) (PEO-b-PLA) systems have been observed to assemble into fiber structures with remarkably different properties using different chirality and molecular weight of PLA segments. In this study, dissipative particle dynamics (DPD) simulations were carried out to elaborate the microstructures and properties of pure paclitaxel and paclitaxel-loaded PEO-b-PLA systems. Paclitaxel molecules formed ribbon or fiber like structures in water. With the addition of PEO-b-PDLA, PEO-b-PLLA and their stereocomplex, paclitaxel acted as a template and polymer molecules assembled around the paclitaxel structure to form core/shell structured fibers having a PEO shell. For PEO19-b-PDLA27 and PEO19-b-PLLA27 systems, PLA segments and paclitaxel molecules were distributed homogeneously in the core of fibers based on the hydrophobic interactions. In the stereocomplex formulation, paclitaxel molecules were more concentrated in the inner PLA stereocomplex core, which led to slower release of paclitaxel. By increasing the length of PLA segments (e.g. 8,16,22 and 27), the crystalline structure of paclitaxel was gradually weakened and destroyed, which was further proved by X-ray diffraction studies. All the simulation results agreed well with experimental data, suggesting that the DPD simulations may provide a powerful tool for designing drug delivery systems.

  16. Sustained release of corticosterone in rats affects reactivity, but does not affect habituation to immobilization and acoustic stimuli.

    Science.gov (United States)

    Tanke, Marit A C; Fokkema, Dirk S; Doornbos, Bennard; Postema, Folkert; Korf, Jakob

    2008-07-18

    Depression is often preceded by stressful life events and accompanied with elevated cortisol levels and glucocorticoid resistance. It has been suggested that a major depressive disorder may result from impaired coping with and adaptation to stress. The question is whether or not hypothalamus-pituitary-adrenal (HPA)-axis dysfunction influences the process of adaptation. We examined the effect of a dysregulated HPA-axis on the adaptation to acoustic stimuli in rats with or without preceding restraint stress. HPA-axis function was altered via slow release of corticosterone (CORT, 90 mg) from subcutaneously implanted pellets for 7 or 14 days. The rate of body temperature increases during restraint (10 min) and the response to acoustic stimuli (of 80+120 dB) were used to quantify daily stress reactivity. Rats habituated to either stress regardless of CORT treatment. CORT treatment combined with restraint decreased the initial reactivity and the variability in response, but the rate of habituation was not influenced. These results show that suppressing normal HPA-axis function by chronic exposure to CORT does affect the course of habituation, but not habituation per se. This implies that altered HPA-axis function in depressed patients may not be causally related to stress coping, but instead may influence the course of the disorder.

  17. Biocompatible long-sustained release oil-core polyelectrolyte nanocarriers: From controlling physical state and stability to biological impact.

    Science.gov (United States)

    Szczepanowicz, Krzysztof; Bazylińska, Urszula; Pietkiewicz, Jadwiga; Szyk-Warszyńska, Lilianna; Wilk, Kazimiera A; Warszyński, Piotr

    2015-08-01

    It has been generally expected that the most applicable drug delivery system (DDS) should be biodegradable, biocompatible and with incidental adverse effects. Among many micellar aggregates and their mediated polymeric systems, polyelectrolyte oil-core nanocarriers have been found to successfully encapsulate hydrophobic drugs in order to target cells and avoid drug degradation and toxicity as well as to improve drug efficacy, its stability, and better intracellular penetration. This paper reviews recent developments in the formation of polyelectrolyte oil-core nanocarriers by subsequent multilayer adsorption at micellar structures, their imaging, physical state and stability, drug encapsulation and applications, in vitro release profiles and in vitro biological evaluation (cellular uptake and internalization, biocompatibility). We summarize the recent results concerning polyelectrolyte/surfactant interactions at interfaces, fundamental to understand the mechanisms of formation of stable polyelectrolyte layered structures on liquid cores. The fabrication of emulsion droplets stabilized by synergetic surfactant/polyelectrolyte complexes, properties, and potential applications of each type of polyelectrolyte oil-core nanocarriers, including stealth nanocapsules with pegylated shell, are discussed and evaluated. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. Encapsulation of grape seed extract in polylactide microcapsules for sustained bioactivity and time-dependent release in dental material applications.

    Science.gov (United States)

    Yourdkhani, Mostafa; Leme-Kraus, Ariene Arcas; Aydin, Berdan; Bedran-Russo, Ana Karina; White, Scott R

    2017-06-01

    To sustain the bioactivity of proanthocyanidins-rich plant-derived extracts via encapsulation within biodegradable polymer microcapsules. Polylactide microcapsules containing grape seed extract (GSE) were manufactured using a combination of double emulsion and solvent evaporation techniques. Microcapsule morphology, size distribution, and cross-section were examined via scanning electron microscopy. UV-vis measurements were carried out to evaluate the core loading and encapsulation efficiency of microcapsules. The bioactivity of extracts was evaluated after extraction from capsules via solvent partitioning one week or one year post-encapsulation process. Fifteen human molars were cut into 7mm×1.7mm×0.5mm thick mid-coronal dentin beams, demineralized, and treated with either encapsulated GSE, pristine GSE, or left untreated. The elastic modulus of dentin specimens was measured based on three-point bending experiments as an indirect assessment of the bioactivity of grape seed extracts. The effects of the encapsulation process and storage time on the bioactivity of extracts were analyzed. Polynuclear microcapsules with average diameter of 1.38μm and core loading of up to 38wt% were successfully manufactured. There were no statistically significant differences in the mean fold increase of elastic modulus values among the samples treated with encapsulated or pristine GSE (p=0.333), or the storage time (one week versus one year storage at room temperature, p=0.967). Polynuclear microcapsules containing proanthocyanidins-rich plant-derived extracts were prepared. The bioactivity of extracts was preserved after microencapsulation. Copyright © 2017 The Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

  19. Simulating reservoir releases to mitigate climate impacts on fish sustainability below Shasta Lake using stochastic and mechanistic modeling approaches

    Science.gov (United States)

    Sapin, J. R.; Saito, L.; Rajagopalan, B.; Caldwell, R. J.

    2013-12-01

    meeting downstream temperature targets. Using the methods outlined, we hope to provide seasonal and long-term forecasting considerations to reservoir managers to maintain a sustainable cold-water supply for salmon proliferation.

  20. Sustained reduction of diversion and abuse after introduction of an abuse deterrent formulation of extended release oxycodone.

    Science.gov (United States)

    Severtson, Stevan Geoffrey; Ellis, Matthew S; Kurtz, Steven P; Rosenblum, Andrew; Cicero, Theodore J; Parrino, Mark W; Gilbert, Michael K; Buttram, Mance E; Dasgupta, Nabarun; BucherBartelson, Becki; Green, Jody L; Dart, Richard C

    2016-11-01

    The development of abuse deterrent formulations is one strategy for reducing prescription opioid misuse and abuse. A putative abuse deterrent formulation of oxycodone extended release (OxyContin(®)) was introduced in 2010. Early reports demonstrated reduced abuse and diversion, however, an analysis of social media found 32 feasible methods to circumvent the abuse deterrent mechanism. We measured trends of diversion, abuse and street price of OxyContin to assess the durability of the initial reduction in abuse. Data from the Poison Center Program, Drug Diversion Program, Opioid Treatment Program, Survey of Key Informant Patients Program and StreetRx program of the Researched Abuse, Diversion, and Addiction-Related Surveillance (RADARS(®)) System were used. The average quarterly rates of abuse and diversion for OxyContin were compared from before reformulation to the rate in second quarter 2015. Rates were adjusted for population using US Census data and drug availability. OxyContin abuse and diversion declined significantly each quarter after reformulation and persisted for 5 years. The rate of abuse of other opioid analgesics increased initially and then decreased, but to lesser extent than OxyContin. Abuse through both oral and non-oral routes of self-administration declined following the reformulation. The geometric mean difference in the street price of reformulated OxyContin was 36% lower than the reformulated product in the year after reformulation. Despite methods to circumvent the abuse deterrent mechanism, abuse and diversion of OxyContin decreased promptly following the introduction of a crush- and solubility- resistant formulation and continued to decrease over the subsequent 5 years. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  1. Dose proportionality and pharmacokinetics of carvedilol sustained-release formulation: a single dose-ascending 10-sequence incomplete block study

    Directory of Open Access Journals (Sweden)

    Kim YH

    2015-06-01

    Full Text Available Yo Han Kim,1 Hee Youn Choi,1 Yook-Hwan Noh,1 Shi Hyang Lee,1 Hyeong-Seok Lim,1 Chin Kim,2 Kyun-Seop Bae11Department of Clinical Pharmacology and Therapeutics, College of Medicine, University of Ulsan, Asan Medical Center, 2Chong Kun Dang Clinical Research and Clinical Epidemiology and Medical Information, CKD Pharmaceuticals, Seoul, Republic of KoreaBackground: Carvedilol is a third-generation β-blocker indicated for congestive heart failure and high blood pressure. The aim of this study was to investigate the dose proportionality of the carvedilol sustained-release (SR formulation in healthy male subjects.Methods: An open-label, single dose-ascending, 10-sequence, 3-period balanced incomplete block study was performed using healthy male subjects. In varying sequences, each subject received three of five carvedilol SR formulations (8, 16, 32, 64, or 128 mg once. The treatment periods were separated by a washout period of 7 days. Serial blood samples were collected up to 48 h after dosing. The plasma concentrations of carvedilol were determined by using validated liquid chromatography–tandem mass spectrometry. Pharmacokinetic parameters including the area under the plasma concentration–time curve (AUC from time 0 to the last measurable time (AUClast, AUC extrapolated to infinity (AUCinf, and the measured peak plasma concentration (Cmax were obtained by noncompartmental analysis. Dose proportionality was evaluated if the ln–ln plots of AUClast, AUCinf, and Cmax versus dose were linear and the 90% confidence intervals (CIs of the slopes were within 0.9195 and 1.0805. Tolerability was assessed by vital signs, electrocardiogram, clinical laboratory tests, and monitoring of adverse events (AEs throughout the study.Results: A total of 31 subjects were enrolled, and 30 completed the study. The assessment of dose proportionality meets the statistical criteria; the point estimates of slope were 1.0104 (90% CI: 0.9849–1.0359 for AUClast, 1

  2. A double-blind crossover comparison study of the safety and efficacy of mebeverine with mebeverine sustained release in the treatment of irritable bowel syndrome.

    Science.gov (United States)

    Van Outryve, M; Mayeur, S; Meeus, M A; Rosillon, D; Hendrickx, B; Ceuppens, M

    1995-10-01

    The safety and efficacy of the sustained release (SR) mebeverine capsule was compared to the standard plain mebeverine capsule in the treatment of 60 patients suffering from irritable bowel syndrome. Patients, with a score of at least 44 on the Kruis scale, were randomized into a two-period crossover trial. Each treatment period lasted for 6 weeks during which the patients took mebeverine plain 135 mg, two capsules t.i.d., or mebeverine sustained release 200 mg (SR), two capsules b.i.d. After 6 weeks of each treatment, both treatments were regarded 'effective' or 'very effective' by the patient as well as the investigator in more than 80% of the cases. After 3 weeks of the first treatment, the disease score was rated light in 73% of the patients with both medications. After 6 weeks, nine patients (33%) were symptom-free with mebeverine plain, and five (18%) with mebeverine SR. During the second treatment period the number of symptom-free cases reached about 40% with both formulations. Considering the clinical general improvement, more than 70% of all patients had improved after 3 weeks of the first treatment. An additional improvement was reported in 13 patients with mebeverine plain and in 10 patients with mebeverine SR after the next 3 weeks. Abdominal pain was still present in more than 50% of patients but with lower intensity compared with baseline values. Mean scores of efficacy were very similar for both treatments after 3 and 6 weeks (2.0 for mebeverine plain vs. 1.9 for mebeverine SR). The statistical comparison of all scores between the two formulations did not show a significant difference at any time. Very few adverse events were noted and a causal relationship with the study medications was judged as improbable or definitely unrelated. Compliance was close to 100% for most of the patients. The results of the present study indicate that the mebeverine SR capsule provides equivalent efficacy and tolerance to mebeverine plain in the treatment of irritable

  3. Evaluation of a 12-Hour Sustained-Release Acetaminophen (Paracetamol) Formulation: A Randomized, 3-Way Crossover Pharmacokinetic and Safety Study in Healthy Volunteers.

    Science.gov (United States)

    Yue, Yong; Collaku, Agron; Liu, Dongzhou J

    2018-01-01

    Acetaminophen (paracetamol) is a first-line treatment for mild and moderate pain. A twice-daily sustained-release (SR) formulation may be more convenient for chronic users than standard immediate-release (IR) acetaminophen. This randomized, 3-way crossover study evaluated pharmacokinetics and safety of single-dose 1500- and 2000-mg SR acetaminophen formulations and 2 doses of IR acetaminophen 1000 mg given 6 hours apart in healthy adults (n = 14). Primary outcome was time that plasma acetaminophen concentration was ≥4 μg/mL (T C≥4μg/mL ). Key secondary outcomes were area under the plasma concentration-time curve (AUC) from time 0 to time t, when plasma acetaminophen was detectable (AUC 0-t ), AUC from 0 to infinity (AUC 0-inf ), and maximum plasma acetaminophen concentration (C max ). T C≥4μg/mL from 2000-mg SR acetaminophen was similar to that from 2 doses of IR acetaminophen, whereas T C≥4μg/mL for 1500-mg SR acetaminophen was significantly shorter than that for IR acetaminophen (P = .004). The extent of acetaminophen absorption from 2000-mg SR and 2 doses of the IR formulation was similar and within bioequivalence limits with regard to AUC 0-12 , AUC 0-t , and AUC 0-inf . The extent of acetaminophen absorption from 1500-mg SR was significantly lower than that from IR acetaminophen. The 2000-mg SR represents a potential candidate formulation for 12-hour dosing with acetaminophen. © 2017, The American College of Clinical Pharmacology.

  4. Sustained Nitric Oxide-Releasing Nanoparticles Interfere with Methicillin-Resistant Staphylococcus aureus Adhesion and Biofilm Formation in a Rat Central Venous Catheter Model.

    Science.gov (United States)

    Mihu, Mircea Radu; Cabral, Vitor; Pattabhi, Rodney; Tar, Moses T; Davies, Kelvin P; Friedman, Adam J; Martinez, Luis R; Nosanchuk, Joshua D

    2017-01-01

    Staphylococcus aureus is frequently isolated in the setting of infections of indwelling medical devices, which are mediated by the microbe's ability to form biofilms on a variety of surfaces. Biofilm-embedded bacteria are more resistant to antimicrobial agents than their planktonic counterparts and often cause chronic infections and sepsis, particularly in patients with prolonged hospitalizations. In this study, we demonstrate that sustained nitric oxide-releasing nanoparticles (NO-np) interfere with S. aureus adhesion and prevent biofilm formation on a rat central venous catheter (CVC) model of infection. Confocal and scanning electron microscopy showed that NO-np-treated staphylococcal biofilms displayed considerably reduced thicknesses and bacterial numbers compared to those of control biofilms in vitro and in vivo, respectively. Although both phenotypes, planktonic and biofilm-associated staphylococci, of multiple clinical strains were susceptible to NO-np, bacteria within biofilms were more resistant to killing than their planktonic counterparts. Furthermore, chitosan, a biopolymer found in the exoskeleton of crustaceans and structurally integrated into the nanoparticles, seems to add considerable antimicrobial activity to the technology. Our findings suggest promising development and translational potential of NO-np for use as a prophylactic or therapeutic against bacterial biofilms on CVCs and other medical devices. Copyright © 2016 American Society for Microbiology.

  5. Design and in vitro evaluation of self-assembled indometacin prodrug nanoparticles for sustained/controlled release and reduced normal cell toxicity

    Science.gov (United States)

    Lin, Jinyan; Pan, Zhou; Song, Liang; Zhang, Yanmei; Li, Yang; Hou, Zhenqing; Lin, Changjian

    2017-12-01

    Despite the great efficacy of indomethacin (IND) as an anti-inflammatory agent, its clinical translation has been obstructed by the water insolubility, severe side effects, and exceedingly low bioavailability. Indomethacin prodrug-based nanoparticles (NPs) combining the strengths of both nanotechnology and prodrugs that might overcome this crucial problem are presented. Here, using the carbodiimide-mediated couple reaction, IND was conjugated to clinically approved poly(ethylene glycol) (PEG) polymer via peptide linkage that was cleavaged in the presence of cathepsin B, which was significantly induced after inflammatory. The synthesized IND-PEG-IND conjugate was characterized by UV-vis, FTIR, 1H NMR, XRD, and MALDI-TOF-MS analyses. For its intrinsic amphiphilic property, the IND prodrug self-assembled into NPs in aqueous solution and served two roles-as an anti-inflammatory prodrug and a drug carrier. The constructed IND-PEG-IND NPs had naoscaled particle size of approximately 80 nm, negative surface, spherical shape, good water-dispersity, and high and fixed drug-loading content of 20.1 wt%. In addition, IND-PEG-IND NPs demonstrated sustained and cathepsin B-controlled drug release behavior. More importantly, IND-PEG-IND NPs significantly reduced the acute totoxicity agaist normal osteoblast cells and displayed the more potent anti-inflammatory effect against macrophage cells compared to the free IND. Taken together, the nanoprodrug might exhibit increased potency for nanomedicine-prospective therapeutic use in clinical treatement of implant inflammatory diseases.

  6. Bupropion sustained release treatment decreases craving for video games and cue-induced brain activity in patients with Internet video game addiction.

    Science.gov (United States)

    Han, Doug Hyun; Hwang, Jun Won; Renshaw, Perry F

    2010-08-01

    Bupropion has been used in the treatment of patients with substance dependence based on its weak inhibition of dopamine and norepinephrine reuptake. We hypothesized that 6 weeks of bupropion sustained release (SR) treatment would decrease craving for Internet game play as well as video game cue-induced brain activity in patients with Internet video game addiction (IAG). Eleven subjects who met criteria for IAG, playing StarCraft (>30 hr/week), and eight healthy comparison subjects (HC) who had experience playing StarCraft (addition, symptoms of depression, craving for playing the game, and the severity of Internet addiction were evaluated by Beck Depression Inventory, self-report of craving on a 7-point visual analogue scale, and Young's Internet Addiction Scale, respectively. In response to game cues, IAG showed higher brain activation in left occipital lobe cuneus, left dorsolateral prefrontal cortex, and left parahippocampal gyrus than HC. After a 6 week period of bupropion SR, craving for Internet video game play, total game play time, and cue-induced brain activity in dorsolateral prefrontal cortex were decreased in the IAG. We suggest that bupropion SR may change craving and brain activity in ways that are similar to those observed in individuals with substance abuse or dependence. PsycINFO Database Record 2010 APA, all rights reserved.

  7. Development and validation of a RP-HPLC method for the determination of zidovudine and its related substances in sustained-release tablets.

    Science.gov (United States)

    dos Santos, Jucimary V; de Carvalho, Luís A E Batista; Pina, M Eugénia

    2011-01-01

    A reversed-phase high-performance liquid chromatography (RP-HPLC) method for the rapid and accurate quantification of zidovudine (AZT) in sustained release tablets during stability testing was developed. A Waters RP-18 XTerra™(®) column, using a water:methanol (80:20, v/v%) mobile phase at a flow rate of 1.0 ml min(-1), and UV detection at 266 nm, was employed. The method of validation parameters indicate a linear range of between 40.0 to 220.0 µg ml(-1) with an LOQ of 1.985 µg ml(-1) and an LOD of 0.655 µg ml(-1) for the analyte. The degradation products of AZT were isolated and characterized for the first time. There was a very little decline of antiviral by heat, and AZT did not completely degrade either by acid or alkaline hydrolysis. On the other hand, oxidation caused a higher degradation stress in the drug. Finally, the degradation products resulting from stress studies were not found to interfere with the detection of antiviral, which is an advantage of the presently proposed method.

  8. Sustained-released mixture of vascular endothelial growth factor 165 and fibrin glue strengthens healing of ileal anastomoses in a rabbit model with intraperitoneal infection.

    Science.gov (United States)

    Li, Zhanwu; Wang, Wenjun; Wang, Xiaozhou; Jiang, Lei; Wang, Fengyi; Liu, Qiang

    2017-09-01

    To investigate the effects of a sustained-released mixture of vascular endothelial growth factor 165 (VEGF165) and fibrin glue (FG) local administration on postoperative rabbit ileal anastomoses. One hundred twenty-eight male and female New Zealand white rabbits underwent intraperitoneal infection subsequent ileal anastomosis surgery were divided randomly into 4 groups, including 32 animals in each, applied with saline solution, FG, rhVEGF165 and a mixture of rhVEGF165 with FG (VEGF + FG) on the anastomoses, respectively. The incidences of anastomotic leakage were observed. Histopathological examination for inflammatory infiltration, fibroblast proliferation, and capillary vascular proliferation were performed. Then, bursting pressure and hydroxyproline concentrations were assessed in anastomoses sits on postoperative days 3, 5, 7, and 14. Rabbits in VEGF + FG group had the lowest incidence of leakage (P < 0.05). Histological evaluations revealed that granulation tissue was formed on days 5 after anastomosis; fibroblast proliferation and capillary vascular proliferation were significantly increased on days 7 and 14 in VEGF + FG group. Furthermore, there was a statistically significant difference in the mean bursting pressures between VEGF + FG group and other groups on days 7 and 14 (P < 0.05), and rabbits in VEGF + FG group exhibited a higher concentration than VEGF group (P < 0.05) and FG group (P < 0.05) on day 14. Administration of VEGF165 mixed with FG to ileal anastomosis accelerates wound healing and enhances the anastomosis by increased angiogenesis.

  9. Sustained Release Formulation of Primaquine for Prevention of Relapse of Plasmodium vivax Malaria: A Randomized, Double-Blind, Comparative, Multicentric Study

    Directory of Open Access Journals (Sweden)

    Anil Pareek

    2015-01-01

    Full Text Available Background. Primaquine is used to eradicate latent Plasmodium vivax parasite from liver, with administration of standard dose daily up to 14 days. We studied efficacy, safety, and tolerability of sustained release (SR formulation of primaquine in comparison with conventional primaquine in preventing relapse of P. vivax malaria. Methods. Microscopically confirmed cases of P. vivax malaria received chloroquine therapy for three days. Aparasitemic and asymptomatic patients were then randomized to receive either conventional primaquine 15 mg for 14 days or primaquine SR 15 mg for 14 days, or primaquine SR 30 mg for seven days. Results. Of the 360 patients, who received chloroquine therapy, 358 patients were randomized. Two-hundred eighty-eight patients completed six-month follow-up and four patients (three: conventional primaquine 15 mg (2.86%, one: primaquine SR 30 mg (0.93% showed relapse confirmed by PCR genotyping. Drug compliance was significantly better in primaquine SR 30 mg group (95.57%, p=0.039 without any serious adverse events. Conclusion. Primaquine SR 15 mg and primaquine SR 30 mg could be an effective alternative to conventional primaquine 15 mg due to their comparable cure rates and safety profile. Shorter treatment duration with primaquine SR 30 mg may increase patient compliance and may further reduce relapse rates. Clinical Trial Registration. This trial is registered with CTRI/2010/091/000245.

  10. Safety and Efficacy of Banaba-Moringa oleifera-Green Coffee Bean Extracts and Vitamin D3 in a Sustained Release Weight Management Supplement.

    Science.gov (United States)

    Stohs, Sidney J; Kaats, Gilbert R; Preuss, Harry G

    2016-04-01

    This 60-day, 30-subject pilot study examined a novel combination of ingredients in a unique sustained release (Carbopol matrix) tablet consumed twice daily. The product was composed of extracts of banaba leaf, green coffee bean, and Moringa oleifera leaf and vitamin D3. Safety was assessed using a 45-measurement blood chemistry panel, an 86-item self-reported Quality of Life Inventory, bone mineral density, and cardiovascular changes. Efficacy was assessed by calculating a body composition improvement index (BCI) based on changes in dual energy X-ray absorptiometry measured fat mass (FM) and fat-free mass (FFM) as well as between the study group (SG) and a historical placebo group. No changes occurred in any blood chemistry measurements. Positive changes were found in the Quality of Life (QOL) inventory composite scores. No adverse effects were observed. Decreases occurred in FM (p = 0.004) and increases in FFM (p = 0.009). Relative to the historical placebo group, the SG lost more FM (p negative BCI of -2.7 lb. compared with a positive BCI in the SG of 3.4 lb., a 6.1 discordance (p = 0.0009). The data support the safety and efficacy of this unique product and demonstrate importance of using changes in body composition versus scale weight and BMI. © 2016 The Authors Phytotherapy Research Published by John Wiley & Sons Ltd.

  11. In Vitro Sustained Release Study of Gallic Acid Coated with Magnetite-PEG and Magnetite-PVA for Drug Delivery System

    Directory of Open Access Journals (Sweden)

    Dena Dorniani

    2014-01-01

    Full Text Available The efficacy of two nanocarriers polyethylene glycol and polyvinyl alcohol magnetic nanoparticles coated with gallic acid (GA was accomplished via X-ray diffraction, infrared spectroscopy, magnetic measurements, thermal analysis, and TEM. X-ray diffraction and TEM results showed that Fe3O4 nanoparticles were pure iron oxide having spherical shape with the average diameter of 9 nm, compared with 31 nm and 35 nm after coating with polyethylene glycol-GA (FPEGG and polyvinyl alcohol-GA (FPVAG, respectively. Thermogravimetric analyses proved that after coating the thermal stability was markedly enhanced. Magnetic measurements and Fourier transform infrared (FTIR revealed that superparamagnetic iron oxide nanoparticles could be successfully coated with two polymers (PEG and PVA and gallic acid as an active drug. Release behavior of gallic acid from two nanocomposites showed that FPEGG and FPVAG nanocomposites were found to be sustained and governed by pseudo-second-order kinetics. Anticancer activity of the two nanocomposites shows that the FPEGG demonstrated higher anticancer effect on the breast cancer cell lines in almost all concentrations tested compared to FPVAG.

  12. Therapeutic equivalence of diclofenac sustained-released 75 mg tablets and diclofenac enteric-coated 50 mg tablets in the treatment of painful osteoarthritis.

    Science.gov (United States)

    Le Loët, X; Dreiser, R L; Le Gros, V; Febvre, N

    1997-09-01

    Efficacy and tolerability of diclofenac sustained-released (SR) 75 mg tablets taken b.i.d. were compared with that of enteric-coated diclofenac sodium 50 mg tablets given t.i.d. in a seven-day, randomised, double-blind, double-dummy, parallel groups study in 294 outpatients suffering from painful femorotibial or hip osteoarthritis. Primary efficacy criteria were spontaneous joint pain assessed on serial visual analogue scales during the first 36 hours and after 48 hours of treatment. The two treatments had equivalent efficacy since all the 90% confidence intervals of differences between means for pain intensity between the two groups were included within the interval (-10 mm; +10 mm). Rates of overall efficacy judged good to excellent ranged from 74.3-78.5% in both groups. One or more drug-related adverse events, mainly gastrointestinal, was reported by 24.5% and 27.2% of patients in diclofenac SR 75 mg and diclofenac 50 mg groups, respectively. Percentage of good compliance (i.e. > 90%) was higher with diclofenac SR 75 mg (p < 0.001).

  13. Safety of implanting sustained-release 5-fluorouracil into hepatic cross-section and omentum majus after primary liver cancer resection.

    Science.gov (United States)

    Chen, Jiangtao; Zhang, Junjie; Wang, Chenyu; Yao, Kunhou; Hua, Long; Zhang, Liping; Ren, Xuequn

    2016-09-01

    This study was designed to evaluate the short-term safety of implanting sustained-release 5-fluorouracil (5-FU) into hepatic cross-section and omentum majus after primary liver cancer resection and its impact on related indexes of liver. Forty patients were selected and divided into an implantation group (n = 20) and a control group (n = 20). On the first day after admission, first week after surgery, and first month after surgery, fasting venous blood was extracted from patients for measuring hematological indexes. The reduction rate of alpha fetoprotein (AFP) on the first week and first month after surgery was calculated, and moreover, drainage volume of the abdominal cavity drainage tube, length of stay after surgery, and wound healing condition were recorded. We found that levels of alanine aminotransferase, aspartate amino transferase, blood urea nitrogen, creatinine, total bilirubin, albumin, and white blood cells measured on the first week and first month after surgery, length of stay, and wound healing of patients in the two groups had no significant difference (P >0.05). Drainage volume and reduction rate of AFP of two groups were significantly different on the first week and first month after surgery (P liver cancer resection is proved to be safe as it has little impact on related indexes. © The Author(s) 2016.

  14. DEVELOPMENT OF SUSTAINED RELEASE TABLETS ...

    African Journals Online (AJOL)

    2013-12-31

    Dec 31, 2013 ... sample were set from 50C to 3000C using nitrogen as purging gas and the samples were analyzed. Thermograms of ... were as follows: voltage 35 kV, current 20 mA, filter Cu and scanning speed 1°/min. 2.6. ... The solid dispersions of baclofen were prepared by hot melt method with varying concentrations.

  15. Effect of metformin-sustained release therapy on low-density lipoprotein size and adiponectin in the South Indian women with polycystic ovary syndrome

    Directory of Open Access Journals (Sweden)

    D Rama Nagendra Kumar

    2017-01-01

    Full Text Available Objectives: The aim of the study is to compare surrogate markers of cardiovascular disease (CVD risk, such as adiponectin (APN levels and low-density lipoprotein (LDL size, before and after sustained release metformin (Met-SR therapy in women with polycystic ovarian syndrome (PCOS. Methods: Sixty women with PCOS and sixty age-matched controls in the age group 18–45 years were recruited after obtaining informed consent. Women with PCOS were initiated on Met-SR 1 g orally, which was increased to 1.5 g after 2 weeks and continued up to 24 weeks. Demographic data along with family history of type 2 diabetes mellitus, PCOS, and CVD were collected. Lipid profile plasma APN levels and LDL size were measured before and after therapy in the PCOS group. Data analysis was performed using the GraphPad Prism-5 software. Results: Women with PCOS had greater dyslipidemia, lower APN level and LDL size, and increased lipid accumulating product index as compared to controls. After 6 months of Met-SR therapy, women with PCOS demonstrated significant increase in plasma APN levels and LDL size and significant decrease in weight, waist-hip ratio (WHR, waist circumference (WC, and blood pressure (BP. A significant decrease was observed in body mass index (BMI in the overweight and obese PCOS subgroups. Conclusion: Met-SR increases LDL size, APN concentration and decreases weight, WC, WHR, and BP in patients with PCOS. Met-SR may have salutary effects on LDL particle size through effects on APN levels in women with PCOS.

  16. Effects of premedication with sustained-release buprenorphine hydrochloride and anesthetic induction with ketamine hydrochloride or propofol in combination with diazepam on intraocular pressure in healthy sheep.

    Science.gov (United States)

    Gatson, Bonnie J; Pablo, Luisito; Plummer, Caryn E; Granone, Tiffany D

    2015-09-01

    To determine the effects of diazepam combined with ketamine hydrochloride or propofol for induction of anesthesia (IOA) following premedication with sustained-release buprenorphine hydrochloride (SRB) on intraocular pressure (IOP) in sheep. 20 healthy adult sheep. Diazepam with ketamine or propofol was given IV to each of 10 sheep after premedication with SRB (0.01 mg/kg, SC); after > 4 weeks, each sheep received the other induction combination with no premedication. For both eyes, IOPs were measured before premedication (if given), 10 minutes prior to (baseline) and immediately following administration of ketamine or propofol (time of IOA), after endotracheal intubation, and 5 minutes after IOA. Peak end-tidal P(CO2), globe position, and pupillary diameter were also analyzed. Data were not available for all sheep for all anesthetic episodes. Propofol-diazepam administration alone had no significant effect on IOP, whereas there was a significant decrease in IOP immediately following ketamine-diazepam administration alone. At 5 minutes after ketamine-diazepam administration, SRB-premedicated sheep had significantly higher IOP than unpremedicated sheep. Intraocular pressure was significantly higher at baseline, at intubation, and 5 minutes after IOA in SRB-premedicated sheep receiving propofol-diazepam, compared with unpremedicated sheep. Peak end-tidal P(CO2) at intubation was significantly higher in SRB-premedicated sheep. For sheep receiving either anesthetic treatment, IOPs did not differ significantly with or without SRB premedication. Globe position or pupillary diameter and IOP were not significantly related at any time point. Results suggested that both ketamine-diazepam and propofol-diazepam combinations were suitable for IOA without increasing IOP in sheep. The use of SRB should be avoided in sheep when increases in IOP are undesirable.

  17. Effect of Metformin-sustained Release Therapy on Low-density Lipoprotein Size and Adiponectin in the South Indian Women with Polycystic Ovary Syndrome.

    Science.gov (United States)

    Kumar, D Rama Nagendra; Seshadri, Krishna G; Pandurangi, Monna

    2017-01-01

    The aim of the study is to compare surrogate markers of cardiovascular disease (CVD) risk, such as adiponectin (APN) levels and low-density lipoprotein (LDL) size, before and after sustained release metformin (Met-SR) therapy in women with polycystic ovarian syndrome (PCOS). Sixty women with PCOS and sixty age-matched controls in the age group 18-45 years were recruited after obtaining informed consent. Women with PCOS were initiated on Met-SR 1 g orally, which was increased to 1.5 g after 2 weeks and continued up to 24 weeks. Demographic data along with family history of type 2 diabetes mellitus, PCOS, and CVD were collected. Lipid profile plasma APN levels and LDL size were measured before and after therapy in the PCOS group. Data analysis was performed using the GraphPad Prism-5 software. Women with PCOS had greater dyslipidemia, lower APN level and LDL size, and increased lipid accumulating product index as compared to controls. After 6 months of Met-SR therapy, women with PCOS demonstrated significant increase in plasma APN levels and LDL size and significant decrease in weight, waist-hip ratio (WHR), waist circumference (WC), and blood pressure (BP). A significant decrease was observed in body mass index (BMI) in the overweight and obese PCOS subgroups. Met-SR increases LDL size, APN concentration and decreases weight, WC, WHR, and BP in patients with PCOS. Met-SR may have salutary effects on LDL particle size through effects on APN levels in women with PCOS.

  18. Comparison of the efficacy and adverse effects of sustained-release buprenorphine hydrochloride following subcutaneous administration and buprenorphine hydrochloride following oral transmucosal administration in cats undergoing ovariohysterectomy.

    Science.gov (United States)

    Catbagan, Davina L; Quimby, Jessica M; Mama, Khursheed R; Rychel, Jessica K; Mich, Patrice M

    2011-04-01

    To compare the efficacy and adverse effects of sustained-release (SR) buprenorphine following SC administration and buprenorphine following oral transmucosal (OTM) administration in cats undergoing ovariohysterectomy. Animals-21 young healthy female cats. As part of anesthetic premedication (0 hours), 10 cats received buprenorphine (0.02 mg/kg) via OTM administration with additional doses at 12, 24, 36, 48, and 60 hours and 11 cats received an equivalent total dose as a single SC injection of SR buprenorphine (0.12 mg/kg). The SR product contained buprenorphine hydrochloride in a proprietary SR matrix. All other anesthetic dru