WorldWideScience

Sample records for demonstrated sustained release

  1. Evaluation of glibenclamide microspheres for sustained release

    Directory of Open Access Journals (Sweden)

    Kambham Venkateswarlu

    2017-04-01

    Full Text Available Context: Sustained release drug delivery systems are more preferred than the conventional drug delivery systems due to its enhanced bioavailability and patient compliance. Earlier studies reported on glibenclamide (GBCM were not clear and hence, the step has been taken to explore the sustained release drug delivery system of GBCM. Aims: To evaluate the sustained release microspheres obtained of GBCM. Methods: Microspheres were prepared by ionic gelation method using the polymers like Eudragit RS 100 and xanthan gum. Polymers can sustain the drug release from microspheres. The prepared microspheres were subjected to micromeritic studies like Carr’s index, Hausner’s ratio and angle of repose. Results: Micromeritic studies confirmed that the microspheres possessing acceptable flow properties. It was observed from the in vitro release studies, formulations F8 and F9 showed sustained drug release for desired time of 12 h and when compared to F9, formulation F8 showed maximum drug release for 12 h. Conclusions: Results confirmed the formulation F8 consist of the polymers such as Eudragit RS 100 about 150 mg and xanthan gum about 100 mg showed desired sustained release of 12 h with 96.07% and kinetic studies confirmed that the release from microspheres followed non-Fickian diffusion mechanism. Due to its sustained release property, it could enhance the bioavailability of drug thereby improves the patient compliance and expect better treatment than conventional dosage forms.

  2. Bioavailability of sustained-release theophylline formulations.

    Science.gov (United States)

    Bonora Regazzi, M; Rondanelli, R; Vidale, E; Cristiani, D

    1983-05-01

    Sustained-release formulations of theophylline as well as of other drugs are designed to effect a delayed but constant release of the active principle in the gastrointestinal tract, thus ensuring more prolonged blood level curves. This study was made to assess the bioavailability of two sustained-release microencapsulated formulations and one sustained-release Diffucaps formulation, in comparison with an equivalent dose of theophylline solution. As regards bioavailability, none of the three formulations differed significantly from the reference formulation. The blood levels at steady state were estimated on the basis of data obtained after a single-dose study. All three sustained release formulations showed good results after prolonged administration in terms of peaks and troughs. The time duration at which the theophylline plasma levels remain higher than 75% of the maximum steady-state levels, following 12-h dosing interval, was evaluated: for the sustained-release microencapsulated formulations this time duration reaches 100% of the dosing interval. A multiple-dose administration of the sustained-release formulations used in this study should guarantee almost complete time coverage, with blood levels sharply exceeding the minimum threshold level of the theophylline therapeutic range.

  3. Sustained-release from nanocarriers: a review.

    Science.gov (United States)

    Natarajan, Jayaganesh V; Nugraha, Chandra; Ng, Xu Wen; Venkatraman, Subbu

    2014-11-10

    Nanocarriers have been explored for delivering drugs and other bioactive molecules for well over 35years. Since the introduction of Doxil®, a nanoliposomal delivery system for the cancer drug doxorubicin, several products have been approved worldwide. The majority of these products focus on cancer chemotherapy, and utilize the size advantage of nanocarriers to obtain a favourable distribution of the drug carrier in the human body. In general, such carriers do not sustain drug release over more than a few days at best. In this review, we explore the reasons for this, and present an overview of successful research that is capable of generating sustained-release products in non-cancer applications. A variety of nanocarriers have been studied, and their advantages and shortcomings are highlighted in this review. The achievement of sustained release of bioactive molecules opens new doors in nanotherapeutics.

  4. Pharmacokinetic Study on Lovastatin Sustained-release Tablet and Sustained-release Capsule in Begal Dogs

    Institute of Scientific and Technical Information of China (English)

    付琳; 代宗顺; 侯淑贤; 万元胜

    2004-01-01

    This study pharmacokinetically examined the lovastatin sustained-release tablet and sustained release capsule in Beagle dogs. An reversed-phase HPLC method was established for the determination of lovastatin in Beagle dog plasma. Pharmacokinetic findings were compared among three preparation(lovastatin sustained-release tablet, TP; sustained-release capsule, TJ and conventional capsule). Our results showed that the pharmacokinetic parameters in 6 dogs after single-dose oral administration of three perparations were calculated. Tmax , Cmax and MRT revealed significant difference (P<0.05). Relative bioavailability was 111. 5 ± 16. 9 % (TP) and 110.4% ± 9.6%(TJ). The pharmacokinetic parameters in the 6 dogs after multiple-dose oral administration of three perparations, Tmax Cmax MRT and DF had significant difference (P<0. 05); Cav, Cmin and AUC0-24 h displayed no significant difference (P>0.05). It is concluded that the lovastatin sustained-release tablet and sustained-release capsule are able to maintain a sustained-release for 24 h.

  5. SUSTAINED RELEASE ITOPRIDE HYDROCHLORIDE MATRIX TABLET

    Directory of Open Access Journals (Sweden)

    BHUPENDRA, PRAJAPATI, NIKLESH PATEL, HITESH

    2013-09-01

    Full Text Available Oral route gets the highest priority for thedelivery of the drug as well as better patient compliance incase of self delivery dosage formulation. The aim ofpresent investigation was undertaken with the objective offormulating sustain release formulation of Itopridehydrochloride for oral drug delivery. Itopride hydrochlorideis highly water soluble prokinetic drug.Hydroxypropylmethylcellulose K4M (lower viscositygrade and K100M (higher viscosity grade were used as amatrix forming agents to control the release of drug. HPMCK4M and HPMC K100M were used individually as well asin combination with different proportion in the preparationof the Sustained release formulation. 32 factorial designswere applied to the polymer concentration that affects thedrug release profile. Reduced equation for drug release at2hr,6hr,and10hrwere22 1 2 1 Q 37.644 5.41X 3.25X 2.017X ,26 1 2 1 Q 72.367 8.05X 4.4X 3.75X ,and10 1 1 2 90.844 5.8 2.633 2.8 2 Q X X X Xrespectively. Optimized batch F019 shows good tabletproperties like hardness(7-9kg/cm2, thickness(4.48mm,friability(0.024%,assay(99.3% and nearly similar drugrelease profile to the targeted reference drug release profileand it was indicated by similarity factor (f2=86.04.

  6. 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.

  7. Sustained release choline theophyllinate in nocturnal asthma.

    Science.gov (United States)

    Rhind, G B; Connaughton, J J; McFie, J; Douglas, N J; Flenley, D C

    1985-12-07

    Nocturnal wheeze is common in patients with asthma, and slow release theophyllines may reduce symptoms. As theophyllines are stimulants of the central nervous system the effect of 10 days' twice daily treatment with sustained release choline theophyllinate or placebo on symptoms, overnight bronchoconstriction, nocturnal oxygen saturation, and quality of sleep were studied in a double blind crossover study in nine stable patients with nocturnal asthma (five men, four women, age range 23-64 years; forced expiratory volume in one second (FEV1) 0.85-3.8 1; vital capacity 1.95-6.1 1). When treated with the active drug all patients had plasma theophylline concentrations of at least 28 mmol/l (5 micrograms/ml) (peak plasma theophylline concentrations 50-144 mmol/l (9-26 micrograms/ml]. Morning FEV1 was higher when treated with sustained release choline theophyllinate (2.7 (SEM 0.3) 1) than placebo (2.1 (0.3) 1) (p less than 0.01). Both daytime and nocturnal symptoms were reduced when the patients were treated with sustained release choline theophyllinate and subjective quality of sleep was improved (p less than 0.002). When treated with the active drug, however, quality of sleep determined by electroencephalography deteriorated with an increase in wakefulness and drowsiness (p less than 0.05) and a reduction in non-rapid eye movement sleep (p less than 0.005). Treatment with choline theophyllinate had no effect on either the occurrence or the severity of transient nocturnal hypoxaemic episodes or apnoeas or hypopnoeas. In conclusion, sustained release choline theophyllinate prevents overnight bronchoconstriction, but impairs quality of sleep defined by electroencephalography.

  8. Solid lipid extrusion of sustained release dosage forms.

    Science.gov (United States)

    Reitz, Claudia; Kleinebudde, Peter

    2007-09-01

    The applicability of the solid lipid extrusion process as preparations method for sustained release dosage forms was investigated in this study. Two lipids with similar melting ranges but of different composition, glyceryl palmitostearate (Precirol ATO 5) and glyceryl trimyristate (Dynasan 114), and mixtures of each lipid with 50% or 75% theophylline were extruded at temperatures below their melting ranges. Extrudates were analyzed using differential scanning calorimetry, scanning electron microscopy, porosity measurements and in vitro drug dissolution studies. The possibility of processing lipids by softening instead of complete melting and without subsequent formation of low-melting, metastable polymorphs could be demonstrated. Extrudates based on formulations of glyceryl palmitostearate/theophylline (50:50) and glyceryl trimyristate/theophylline (50:50) showed sustained release properties. An influence of extrusion conditions on the matrix structure was shown for extrudates based on a mixture of glyceryl trimyristate and theophylline (50:50). Glyceryl trimyristate tended to solidify in porous structures after melting. Exceeding a material temperature of 50.5 degrees C led to porous extrudate matrices with a faster drug release. The production of novel, non porous sustained release matrices was possible at a material temperature of 49.5 degrees C. Extrudates based on glyceryl trimyristate/theophylline (50:50) only slight changes in melting enthalpy and stable drug release profiles.

  9. Sustained-release naltrexone for opioid dependence.

    Science.gov (United States)

    Lobmaier, P; Kornør, H; Kunøe, N; Bjørndal, A

    2008-04-16

    Naltrexone is an opioid antagonist which effectively blocks heroin effects. Since opioid dependence treatment with naltrexone tablets suffers from high dropout rates, several depot injections and implants are under investigation. Sustained-release formulations are claimed to be effective, but a systematic review of the literature is lacking. To evaluate the effectiveness of sustained-release naltrexone for opioid dependence and its adverse effects in different study populations. The following databases were searched from their inception to November 2007: Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, CINAHL, LILACS, PsycINFO, ISI Web of Science, trial database at http://clinicaltrials.gov, available NIDA monographs, CPDD and AAAP conference proceedings. The reference lists of identified studies, published reviews and relevant web sides were searched manually. Study authors and drug companies were contacted to obtain any unpublished material or missing data. To evaluate effectiveness only RCTs were included. To evaluate safety, any clinical trial reporting adverse effects was assessed. Treatment condition was extended to include alcohol dependent subjects and healthy volunteers. Reviewers independently evaluated the reports, rated methodological quality and extracted data. Analyses were performed separately for opioid dependent, alcohol dependent and healthy participants. Foe effectiveness, one report met inclusion criteria. Two dosages of naltrexone depot injections (192 and 384 mg) were compared to placebo. High-dose significantly increased days in treatment compared to placebo (WMD 21.00, 95% CI 10.68 to 31.32, p<0.0001). High-dose compared to low-dose significantly increased days in treatment (WMD 12.00, 95% CI 1.69 to 22.31, p=0.02). Number of patients retained in treatment did not show significant differences between groups. For adverse effects, seventeen reports met inclusion criteria analyses, six were RCTs. Side effects were significantly

  10. Lyophilized Oral Sustained Release Polymeric Nanoparticles of Nateglinide

    National Research Council Canada - National Science Library

    Kaleemuddin, Mohammad; Srinivas, Prathima

    2013-01-01

    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...

  11. 21 CFR 520.1920 - Prochlorperazine, isopropamide sustained release capsules.

    Science.gov (United States)

    2010-04-01

    ... capsules. 520.1920 Section 520.1920 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... § 520.1920 Prochlorperazine, isopropamide sustained release capsules. (a) Specifications. Prochlorperazine, isopropamide sustained release capsules contain either: (1) 3.33 milligrams of prochlorperazine...

  12. Development of enteric coated sustained release minitablets containing mesalamine

    Directory of Open Access Journals (Sweden)

    Dayse Fernanda de Souza

    2013-09-01

    Full Text Available 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, using mesalamine as a model drug. Polyox® WSR 1105 was the polymer used in the matrix system and Eudragit® L30D55 was used as a pH-dependent polymer. The minitablets (with 20%, 30% or 40% Polyox® concentration were prepared by dry granulation, which led to good quality minitablets. The developed minitablets were coated in a fluidized bed at 8% of the coating level. Dissolution studies were performed in media that simulated the gastrointestinal tract (pH 1.4, 6.0 and 7.2 and showed that formulations with higher Polyox® concentrations were capable of retaining the drug release in pH 1.4. All formulations prolonged the drug release and presented zero-order kinetic behaviour. The Korsmeyer-Peppas model demonstrated that formulations with 20% or 30% of polymer exhibited anomalous transport behaviour, whilst the 40% sample exhibited super case II model transportation. Dissolution efficiency showed that only the formulations containing 20% and 40% polymer could be considered statistically different.

  13. Analgesic tolerance without demonstrable opioid-induced hyperalgesia: a double-blinded, randomized, placebo-controlled trial of sustained-release morphine for treatment of chronic nonradicular low-back pain.

    Science.gov (United States)

    Chu, Larry F; D'Arcy, Nicole; Brady, Caitlin; Zamora, Abigail Kathleen; Young, Chelsea Anne; Kim, Julie Eunwoo; Clemenson, Anna Marie; Angst, Martin S; Clark, J David

    2012-08-01

    Although often successful in acute settings, long-term use of opioid pain medications may be accompanied by waning levels of analgesic response not readily attributable to advancing underlying disease, necessitating dose escalation to attain pain relief. Analgesic tolerance, and more recently opioid-induced hyperalgesia, have been invoked to explain such declines in opioid effectiveness over time. Because both phenomena result in inadequate analgesia, they are difficult to distinguish in a clinical setting. Patients with otherwise uncomplicated low-back pain were titrated to comfort or dose-limiting side effects in a prospective, randomized, double-blind, placebo-controlled clinical trial using sustained-release morphine or weight-matched placebo capsules for 1 month. A total of 103 patients completed the study, with an average end titration dose of 78 mg morphine/d. After 1 month, the morphine-treated patients developed tolerance to the analgesic effects of remifentanil, but did not develop opioid-induced hyperalgesia. On average, these patients experienced a 42% reduction in analgesic potency. The morphine-treated patients experienced clinically relevant improvements in pain relief, as shown by a 44% reduction in average visual analogue scale pain levels and a 31% improvement in functional ability. The differences in visual analogue scale pain levels (P = .003) and self-reported disability (P = .03) between both treatment groups were statistically significant. After 1 month of oral morphine therapy, patients with chronic low-back pain developed tolerance but not opioid-induced hyperalgesia. Improvements in pain and functional ability were observed.

  14. FORMULATION AND EVALUATION OF NIFEDIPINE SUSTAINED RELEASE PELLETS

    Directory of Open Access Journals (Sweden)

    T Akelesh

    2011-08-01

    Full Text Available Nifedipine is a dihydropyridine derivative effectively used in management of various cardio vascular diseases in long-term therapy. The main objective of this work is formulation of Nifedipine sustained release capsules. This drug has low half life of 2 hr and is rapidly eliminated. Nifedipine is practically insoluble in water. Solubility of drug plays a major role in absorption and ultimately affects bioavailability. As it is poorly soluble it shows irregular bioavailability upon oral administration. Nifedipine lacks to maintain its concentration at site of action and side effects are more in conventional dosage form. Hence to minimize these affects we found it as an excellent candidate for sustained released oral drug delivery system. Drug release from marketed tablet modified release formulation showed 98.27% and Nifedipine sustained release pellets in capsules showed 98.80%. After stability studies sustained release capsules showed 99.18%. It is concluded that formulation F9 sustained release pellets in capsule was concluded as superior than marketed sustained release tablet formulation. Among the different formulations prepared, trial no F9 with ethyl cellulose N20 of 0.5% concentration and HPMC E5 with 20% concentration was found to have satisfactory dissolution profile.

  15. "Sustained release formulation of Metoclopramide Hydrochloride "

    Directory of Open Access Journals (Sweden)

    Dabbagh MA

    2000-08-01

    Full Text Available In this research, several formulations containing, an anti emetic agent (Metoclopramide hydrochloride, a hydrophilic polymer (hydroxypropylmethylcellulose and a hydrophobic polymer (ethylcellulose 10 cP were prepared by direct compression. Different factors such as: the effect of different ratios of the polymers, particle size, pressure force and differences of release in acidic and distilled water as media were investigated. After developing the ideal formulation, the effect of changing the ratio of drug in core: coating on the formulation was investigated. Coating of tablets with ethylcellulose, changed the release mechanism of drug and shifted it to near zero order release. The results showed that except when matrices were coated with ethylcellulose, drug release was proportioned to the square root of time, which might be due to the change of release pattern from matrix to reservoir system.

  16. CURRENT ADVANCES IN SUSTAINED-RELEASE INJECTABLE PREPARATIONS

    Directory of Open Access Journals (Sweden)

    Liandong Hu*, Hailei Zhang, and Weihua Song

    2012-09-01

    Full Text Available In recent years, there has been a great deal of interests in developing sustained-release systems which can prolong the therapeutic effect, decrease adverse side effects, and reduce administration frequency. Nowadays, the oral sustained-release preparations account for a larger market share comparing to other sustained-release forms, mainly because of its noninvasive pain-free administration. However, the hostile environment of gastrointestinal tract and first-pass effect may lead to low bioavailability of some drugs, such as some proteins, peptides, and hormones. In this paper, the latest research progresses of some new-model sustained-release injectable dosage forms were introduced, including microsphere, microcapsule, liposome, polymeric micelle, and in situ forming system.

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

    African Journals Online (AJOL)

    Tropical Journal of Pharmaceutical Research October 2015; 14(10): 1749-1754 ... prolonged drug release and improvement in motor activity after spinal injuries. Methods: Matrix .... The friability test was performed using a Roche friabilator ...

  18. Optimization of sustained release aceclofenac microspheres using response surface methodology.

    Science.gov (United States)

    Deshmukh, Rameshwar K; Naik, Jitendra B

    2015-03-01

    Polymeric microspheres containing aceclofenac were prepared by single emulsion (oil-in-water) solvent evaporation method using response surface methodology (RSM). Microspheres were prepared by changing formulation variables such as the amount of Eudragit® RS100 and the amount of polyvinyl alcohol (PVA) by statistical experimental design in order to enhance the encapsulation efficiency (E.E.) of the microspheres. The resultant microspheres were evaluated for their size, morphology, E.E., and in vitro drug release. The amount of Eudragit® RS100 and the amount of PVA were found to be significant factors respectively for determining the E.E. of the microspheres. A linear mathematical model equation fitted to the data was used to predict the E.E. in the optimal region. Optimized formulation of microspheres was prepared using optimal process variables setting in order to evaluate the optimization capability of the models generated according to IV-optimal design. The microspheres showed high E.E. (74.14±0.015% to 85.34±0.011%) and suitably sustained drug release (minimum; 40% to 60%; maximum) over a period of 12h. The optimized microspheres formulation showed E.E. of 84.87±0.005 with small error value (1.39). The low magnitudes of error and the significant value of R(2) in the present investigation prove the high prognostic ability of the design. The absence of interactions between drug and polymers was confirmed by Fourier transform infrared (FTIR) spectroscopy. Differential scanning calorimetry (DSC) and X-ray powder diffractometry (XRPD) revealed the dispersion of drug within microspheres formulation. The microspheres were found to be discrete, spherical with smooth surface. The results demonstrate that these microspheres could be promising delivery system to sustain the drug release and improve the E.E. thus prolong drug action and achieve the highest healing effect with minimal gastrointestinal side effects.

  19. Optimization of sustained release aceclofenac microspheres using response surface methodology

    Energy Technology Data Exchange (ETDEWEB)

    Deshmukh, Rameshwar K.; Naik, Jitendra B., E-mail: jitunaik@gmail.com

    2015-03-01

    Polymeric microspheres containing aceclofenac were prepared by single emulsion (oil-in-water) solvent evaporation method using response surface methodology (RSM). Microspheres were prepared by changing formulation variables such as the amount of Eudragit® RS100 and the amount of polyvinyl alcohol (PVA) by statistical experimental design in order to enhance the encapsulation efficiency (E.E.) of the microspheres. The resultant microspheres were evaluated for their size, morphology, E.E., and in vitro drug release. The amount of Eudragit® RS100 and the amount of PVA were found to be significant factors respectively for determining the E.E. of the microspheres. A linear mathematical model equation fitted to the data was used to predict the E.E. in the optimal region. Optimized formulation of microspheres was prepared using optimal process variables setting in order to evaluate the optimization capability of the models generated according to IV-optimal design. The microspheres showed high E.E. (74.14 ± 0.015% to 85.34 ± 0.011%) and suitably sustained drug release (minimum; 40% to 60%; maximum) over a period of 12 h. The optimized microspheres formulation showed E.E. of 84.87 ± 0.005 with small error value (1.39). The low magnitudes of error and the significant value of R{sup 2} in the present investigation prove the high prognostic ability of the design. The absence of interactions between drug and polymers was confirmed by Fourier transform infrared (FTIR) spectroscopy. Differential scanning calorimetry (DSC) and X-ray powder diffractometry (XRPD) revealed the dispersion of drug within microspheres formulation. The microspheres were found to be discrete, spherical with smooth surface. The results demonstrate that these microspheres could be promising delivery system to sustain the drug release and improve the E.E. thus prolong drug action and achieve the highest healing effect with minimal gastrointestinal side effects. - Highlights: • Aceclofenac microspheres

  20. In vitro study on sustained release capsule formulation of acetazolamide.

    Science.gov (United States)

    Pandey, V P; Kannan, K; Manavalan, R; Desai, N

    2003-10-01

    In the present study formulation of sustained release capsule of acetazolamide 250 mg was tried using nonpareil seeds. Nonpareil seeds were coated with drug, polyvinylpyrrolidone, glyceryl monostearate, microcrystalline wax, and glyceryl distearate either individually or in combination to achieve sustained release capsule 250 mg. In successful formulation 20% drug coated pellets and 80% wax coated pellets were taken. Wax coated pellets for successful formulation contained coating of microcrystalline wax and glyceryl distearate on drug coated pellets of the same concentration of 1.6% w/w. Successful formulated sustained release capsule 250 mg of acetazolamide was compared in in vitro study with theoretical sustained release formulation suggested by wagner and one marketed sustained release capsule 250 mg. Formulated capsule showed result superior to or on par with marketed capsule. For successful formulation pellets were filled in '1' size hard gelatin capsule and stability study was carried out in hot air over at room temperature and 45 degrees C for 5 weeks. The formulation was found stable in respect of drug content and release rate.

  1. The use of solid lipid nanoparticles for sustained drug release.

    Science.gov (United States)

    Attama, Anthony A; Umeyor, Chukwuebuka E

    2015-01-01

    Novel solid lipid drug delivery systems such as solid lipid nanoparticles (SLN) have attracted wide and increasing attention in recent years. It has been sought as an interesting alternative drug delivery carrier system for bioactives for a variety of delivery routes. They show major advantages such as sustained release, improved bioavailability, improved drug incorporation and very wide application. This paper presents a discussion on the production protocols of SLN, lyophilization of SLN and delivery of SLN across the blood-brain barrier. Special attention was also paid to entrapment and release of drugs from SLN and strategies to enhance drug entrapment in SLN for sustained release. Analytical methods for the characterization of SLN were also discussed. Various routes of administration of SLN were presented as well as a consideration of the ethical issues and future prospects in the production and use of SLN for sustained release of bioactives.

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

    Directory of Open Access Journals (Sweden)

    K. H. Janardhana

    2013-12-01

    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.

  3. 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.

  4. A REVIEW ON ADVANCES OF SUSTAINED RELEASE DRUG DELIVERY SYSTEM

    Directory of Open Access Journals (Sweden)

    Sujit Bose

    2013-06-01

    Full Text Available Sustained release matrix tablets facilitate prolonged and continuous drug release and improve the bioavailability of drugs while avoiding unwanted side effects. Ofloxacin is a broad spectrum antibacterial agent used for treating wide range of gram positive and gram negative infections. The goal in designing sustained or controlled delivery systems is to reduce frequency of dosing or to increase the effectiveness of the drug by localization at the site of action, reducing the dose required, providing uniform drug delivery. Sustained release drug administration means not only prolongation of duration of drug delivery, but the term also implies the predictability and reproducibility of drug release kinetics. The controlled release of drug substances and their effective transport to sites of action can be exploited to maximize the beneficial clinical response and to minimize the incidence of unbeneficial adverse reactions and side effects. Oral ingestion has long been the most convenient and commonly employed route of drug delivery. Indeed, for sustained release systems, oral route of administration has received most of the attention with respect to research on physiological and drug constraints as well as design and testing of products.

  5. Formulation and Evaluation of Nateglinide Sustained Release Tablets

    Directory of Open Access Journals (Sweden)

    Sridevi Gowripattapu

    2016-01-01

    Full Text Available The objective of the present investigation was to design suitable sustained release tablet formulation of Nateglinide by using different polymers such as hydroxy propyl methyl cellulose K15M, xanthan gum, guar gum as release rate retarding polymers. The tablets were prepared by direct compression technique. Nateglinide is used as anti diabetic drug. The objective of the treatment is to achieve hypoglycemia, by using an ideal dosage regimen. The sustained release formulation provides extend duration of action in therapeutic range without reaching toxic levels as in the case of conventional dosage forms. The real formulation trails are carried from F1 to F9 in which Drug: Polymer ratio was set as 1:9 respectively. The prepared formulations F1 to F9 were evaluated for pre and post compression characteristics, along with the in vitro dissolution Studies. It was found that the release of drug from F1, F2, and F3 gave the better release than other formulations. In these three formulations F2 showing highest release following first order kinetics. From the Higuchi plot good correlation coefficient was observed showing diffusion mechanism. From the peppas plot it was observed that the release model was non fickian anomalous. The release rate was decreased as polymer concentration increased so it shows that increase in diffusion length of polymer decreases the release rate.

  6. Formulation and Evaluation Of Sustained Release Matrix Tablets of Lornoxicam

    Directory of Open Access Journals (Sweden)

    Syed Namath Ulla

    2011-03-01

    Full Text Available Lornoxicam, a potent non-steroidal anti-inflammatory drug which has short half life, makes the development of sustained release (SR forms extremely advantageous. However, due to its weak acidic nature, its release from SR delivery systems is limited to the lower gastrointestinal tract which consequently leads to a delayed onset of its analgesic action. Therefore, the present investigation of this study was to develop Lornoxicam SR matrix tablets that provide complete drug release that starts in the stomach to rapidly alleviate the painful symptoms and continues in the intestine to maintain analgesic effect. Lornoxicam showed maximum absorption at wavelength 373 nm in 0.1N HCl and 379 nm in pH 6.8. Drug-polymer compatibility studies by FTIR gave confirmation about their purity and showed no interaction between drug and selected polymers. Various formulations were developed by using release rate controlling and gel forming polymers like HPMC (K4M, K15M, K100M by direct compression method. From among all the developed formulations, F1 formulation sustained the drug release for longer period of time as compared to other formulations. So, F1 was selected as the best formulation. It was concluded that the release followed zero order kinetics, as the correlation coefficient (R2 value was higher for zero order release, so the drug release mechanism is controlled release. The best formulation was found to be stable during stability studies for two months. Thus, best formulation satisfied physicochemical parameters and in vitro drug release profile requirements for a sustained drug delivery system.

  7. Sustain-release of various drugs from leucaena leucocephala polysaccharide.

    Science.gov (United States)

    Jeevanandham, S; Sekar, M; Dhachinamoorthi, D; Muthukumaran, M; Sriram, N; Joysaruby, J

    2010-01-01

    This study examines the sustained release behavior of both water-soluble (acetaminophen, caffeine, theophylline and salicylic acid) and water-insoluble (indomethacin) drugs from Leucaena leucocephala seed Gum isolated from Leucaena leucocephala kernel powder. It further investigates the effect of incorporation of diluents like microcrystalline cellulose and lactose on release of caffeine and partial cross-linking of the gum (polysaccharide) on release of acetaminophen. Applying exponential equation, the mechanism of release of soluble drugs was found to be anomalous. The insoluble drug showed near case II or zero-order release mechanism. The rate of release was in the decreasing order of caffeine, acetaminophen, theophylline, salicylic acid and indomethacin. An increase in release kinetics of drug was observed on blending with diluents. However, the rate of release varied with type and amount of blend in the matrix. The mechanism of release due to effect of diluents was found to be anomalous. The rate of release of drug decreased on partial cross-linking and the mechanism of release was found to be super case II.

  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. Sustainable Technology Research and Demonstration Center for Earth Structures

    Directory of Open Access Journals (Sweden)

    Judy Ueda

    2012-10-01

    Full Text Available This is a discussion paper that the authors presented at the International Workshop on Rammed Earth Materials and Sustainable Structures and Hakka Tulou Forum 2011: Structures of Sustainability, 28–31 October 2011, Xiamen University, China. A Sustainable Technology Research and Demonstration Center for Earth Structures is proposed to study, preserve, advance, promote, and implement rammed earth structures. The Center concept including the objectives, scope of activities and benefits of the proposed center are outlined. The Center for Alternative Technology in Wales, UK has been examined as a good base model along with a few successful environmental sustainability initiatives in China. The funding options to establish the proposed center have been discussed. The breadth of activities ultimately depends on funding capability. It is believed that the proposed center development will require significant government support at the initial stage but once corporate sponsorships are in place, the proposed center will potentially become self-supporting. The strategies, for the establishment of the proposed center are also addressed.

  10. Sustainability of orthokeratology as demonstrated by corneal topography.

    Science.gov (United States)

    Kang, Sung Yong; Kim, Bong Kyun; Byun, Young Ja

    2007-06-01

    To determine the sustaining effects of orthokeratology. This study enrolled 58 eyes with moderate myopia. LK-DM lenses (Lucid Korea Dream Lens) were fitted daily for at least eight hours on an overnight regimen. The effects of orthokeratology and it's sustainability throughout the day were recorded twice; immediately after removal in the morning and eight hours later. Sustainability was measured by comparing the changes from morning to afternoon for best uncorrected visual acuity, apical corneal power, keratometric values, spherical equivalent and induced astigmatism. UCVA demonstrated improved values at all follow up periods. Fluctuations during the day stabilized after 4 weeks of lens wear. K values averaged a mean of 42.4 mm at baseline, and reduced to 40.9 mm by week 12. Unaided logMAR visual acuity changed from 0.94+/-0.14 at baseline to -0.11+/-0.17 by week 12. The sustainability of orthokeratology, defined as the difference between morning and afternoon values of unaided logMAR visual acuity, increased from -0.82 on day 1 to -0.11 on week 12. UCVA and spherical refractive error did not change to a significant degree after 4 weeks. Although statistically insignificant minute fluctuations during the day were observed up to week 12, these fluctuations decreased to a statistically significant level after week 4.

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

    African Journals Online (AJOL)

    Erah

    JSS College of Pharmacy, JSS University, Mysore, Karnataka-570015, India. Abstract. Purpose: To develop sustained release matrix tablets of diltiazem hydrochloride (DTZ) using ... channel blocker that is widely prescribed for ..... appearance of new peaks which were absent ... penetration of dissolution media into the.

  12. 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.

  13. Sustained Release Oral Nanoformulated Green Tea for Prostate Cancer

    Science.gov (United States)

    2011-05-01

    prostate cancer progression in humans and is being detected in the serum of patients with prostate diseases including prostatitis , benign prostatic ... hypertrophy , and prostate cancer (4). In our study, we found that there was significant inhibition of secreted PSA levels by 13-36%, 26-54% and 57-72% in...TITLE: Sustained Release Oral Nanoformulated Green Tea for Prostate Cancer PRINCIPAL INVESTIGATOR: Hasan Mukhtar, PhD

  14. Bioequivalence of Progesterone Sustained Release Suppository in Rabbits

    Institute of Scientific and Technical Information of China (English)

    LONG Lihong; HUANG Qun; WU Minghui; HOU Shuxian; DAI Zongshun

    2005-01-01

    To study the bioequivalence of a kind of progesterone sustained release suppository, a randomized cross-over study was conducted in 12 rabbits. A single rectal dose of 2.75 mg/kg progesterone sustained released suppository (tested formulation, T) and progesterone suppository(reference formulation, R) was administered; a multiple dose of 2.75 mg/kg was given up to seven times with an interval of 8 h. Concentrations in serum were determined by a competitive enzyme immunoassay. The main parameters of T were: for single and multiple doses, Cmax was 48.8±11.8ng/mL and 43.5±9.4 ng/mL, Tmax was 0.5±0.3 h and 0.4±0.3 h, AUC(0-24h) was 362.4±143 ng·h·mL-1 and 310.6±70.3ng ·h·mL-1,respectively.The relative bioavailability of T to R were ( 104.2 ±13.4) % and ( 111.4 ± 19. 1 ) %, respectively. Statistical analysis showed that the two formulations were bioequivalent and T had sustained released feature.

  15. 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.

  16. Sustained release of fungicide metalaxyl by mesoporous silica nanospheres

    Science.gov (United States)

    Wanyika, Harrison

    2013-08-01

    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.

  17. 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.

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

    Science.gov (United States)

    Pan, Liping; Qian, Yafang; Cheng, Minlu; Gu, Pan; He, Yanna; Xu, Xiaowen; Ding, Li

    2015-01-01

    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 T max and t 1/2 of propafenone for SR-test were significantly higher than those for IR-reference while C max and AUC were lower demonstrating the sustained release properties of the new formulation. In Study B comparing SR-test with SR-reference the observed C max 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.

  19. Ocular sustained release nanoparticles containing stereoisomeric dipeptide prodrugs of acyclovir.

    Science.gov (United States)

    Jwala, Jwala; Boddu, Sai H S; Shah, Sujay; Sirimulla, Suman; Pal, Dhananjay; Mitra, Ashim K

    2011-04-01

    The objective of this study was to develop and characterize polymeric nanoparticles of appropriate stereoisomeric dipeptide prodrugs of acyclovir (L-valine-L-valine-ACV, L-valine-D-valine-ACV, D-valine-L-valine-ACV, and D-valine-D-valine-ACV) for the treatment of ocular herpes keratitis. Stereoisomeric dipeptide prodrugs of acyclovir (ACV) were screened for bioreversion in various ocular tissues, cell proliferation, and uptake across the rabbit primary corneal epithelial cell line. Docking studies were carried out to examine the affinity of prodrugs to the peptide transporter protein. Prodrugs with optimum characteristics were selected for the preparation of nanoparticles using various grades of poly (lactic-co-glycolic acid) (PLGA). Nanoparticles were characterized for the entrapment efficiency, surface morphology, size distribution, and in vitro release. Further, the effect of thermosensitive gels on the release of prodrugs from nanoparticles was also studied. L-valine-L-valine-ACV and L-valine-D-valine-ACV were considered to be optimum in terms of enzymatic stability, uptake, and cytotoxicity. Docking results indicated that L-valine in the terminal position increases the affinity of the prodrugs to the peptide transporter protein. Entrapment efficiency values of L-valine-L-valine-ACV and L-valine-D-valine-ACV were found to be optimal with PLGA 75:25 and PLGA 65:35 polymers, respectively. In vitro release of prodrugs from nanoparticles exhibited a biphasic release behavior with initial burst phase followed by sustained release. Dispersion of nanoparticles in thermosensitive gels completely eliminated the burst release phase. Novel nanoparticulate systems of dipeptide prodrugs of ACV suspended in thermosensitive gels may provide sustained delivery after topical administration.

  20. Demonstration of Decision Support Tools for Sustainable Development

    Energy Technology Data Exchange (ETDEWEB)

    Shropshire, David Earl; Jacobson, Jacob Jordan; Berrett, Sharon; Cobb, D. A.; Worhach, P.

    2000-11-01

    The Demonstration of Decision Support Tools for Sustainable Development project integrated the Bechtel/Nexant Industrial Materials Exchange Planner and the Idaho National Engineering and Environmental Laboratory System Dynamic models, demonstrating their capabilities on alternative fuel applications in the Greater Yellowstone-Teton Park system. The combined model, called the Dynamic Industrial Material Exchange, was used on selected test cases in the Greater Yellow Teton Parks region to evaluate economic, environmental, and social implications of alternative fuel applications, and identifying primary and secondary industries. The test cases included looking at compressed natural gas applications in Teton National Park and Jackson, Wyoming, and studying ethanol use in Yellowstone National Park and gateway cities in Montana. With further development, the system could be used to assist decision-makers (local government, planners, vehicle purchasers, and fuel suppliers) in selecting alternative fuels, vehicles, and developing AF infrastructures. The system could become a regional AF market assessment tool that could help decision-makers understand the behavior of the AF market and conditions in which the market would grow. Based on this high level market assessment, investors and decision-makers would become more knowledgeable of the AF market opportunity before developing detailed plans and preparing financial analysis.

  1. Effect of glycerol on sustained insulin release from PVA hydrogels and its application in diabetes therapy.

    Science.gov (United States)

    Cai, Yunpeng; Che, Junyi; Yuan, Minglu; Shi, Xiaohong; Chen, Wei; Yuan, Wei-En

    2016-10-01

    The present study aimed to investigate the effects of glycerol on the physical properties and release of an insulin-loaded polyvinyl alcohol (PVA) hydrogel film. The insulin-loaded hydrogel composite film was produced using the freeze-thawing method, after which the in vitro swelling ratio, transmittance and insulin release, and the in vivo pharmacodynamics, of hydrogels containing various volumes of glycerol were investigated. The results demonstrated that the addition of glycerol reduced the swelling ratio and increased the softness of the PVA hydrogel film. An analysis of insulin release in vitro and of the hypoglycemic effects in rats demonstrated that the PVA hydrogel film had a sustained release of insulin and long-acting effect over 10 days. The results of the present study suggested that, as a hydrophilic plasticizer, glycerol was able to enhance the release of insulin in the early stage of release profile by enhancing the formation of water channels, although the total swelling ratio was decreased. Therefore, the insulin-loaded glycerol/PVA hydrogel film may be a promising sustained-release preparation for the treatment of diabetes.

  2. Guar gum, xanthan gum, and HPMC can define release mechanisms and sustain release of propranolol hydrochloride.

    Science.gov (United States)

    Mughal, Muhammad Akhlaq; Iqbal, Zafar; Neau, Steven Henry

    2011-03-01

    The objectives were to characterize propranolol hydrochloride-loaded matrix tablets using guar gum, xanthan gum, and hydroxypropylmethylcellulose (HPMC) as rate-retarding polymers. Tablets were prepared by wet granulation using these polymers alone and in combination, and physical properties of the granules and tablets were studied. Drug release was evaluated in simulated gastric and intestinal media. Rugged tablets with appropriate physical properties were obtained. Empirical and semi-empirical models were fit to release data to elucidate release mechanisms. Guar gum alone was unable to control drug release until a 1:3 drug/gum ratio, where the release pattern matched a Higuchi profile. Matrix tablets incorporating HPMC provided near zero-order release over 12 h and erosion was a contributing mechanism. Combinations of HPMC with guar or xanthan gum resulted in a Higuchi release profile, revealing the dominance of the high viscosity gel formed by HPMC. As the single rate-retarding polymer, xanthan gum retarded release over 24 h and the Higuchi model best fit the data. When mixed with guar gum, at 10% or 20% xanthan levels, xanthan gum was unable to control release. However, tablets containing 30% guar gum and 30% xanthan gum behaved as if xanthan gum was the sole rate-retarding gum and drug was released by Fickian diffusion. Release profiles from certain tablets match 12-h literature profiles and the 24-h profile of Inderal(®) LA. The results confirm that guar gum, xanthan gum, and HPMC can be used for the successful preparation of sustained release oral propranolol hydrochoride tablets.

  3. Formulation, optimization and evaluation of sustained release microsphere of ketoprofen

    Directory of Open Access Journals (Sweden)

    V Chirag Prajapati

    2012-01-01

    Full Text Available The objective of this study is to formulate ketoprofen loaded microspheres of Acrycoat S100 by an o/w emulsion solvent evaporation method. It potently inhibits the enzyme cyclooxygenase resulting in prostaglandin synthesis inhibition. Ketoprofen causes an irritation in the gastrointestinal mucous membrane and possesses a bitter taste and aftertaste. The half-life in plasma is about 1-2hrs. This makes ketoprofen a very good candidate for the formulation of controlled release dosage forms. Ketoprofen microspheres help to protect the gastric mucous membrane from drug irritation and to mask its taste. The prepared microspheres were evaluated for micromeritic properties, particle size, effect of surfactant concentration, percentage yield, incorporation efficiency, drug polymer compatibility (IR and DSC study, scanning electron microscopy and in vitro drug release. The microspheres produced exhibited good encapsulation efficiencies and micromeritic properties. Encapsulation efficiency of microsphere is around 78%. The mean diameters of microspheres were found in required micrometer range. The results of optimized formulations showed a narrow size distribution and smooth surface. The DSC and the FTIR analysis showed the absence of any potent incompatibility between the drug and the polymer. In-vitro release showed 86.4% drug release after 12 hours. Results of present study suggest that Acrycoat S100 loaded microsphere of ketoprofen can be successfully designed to develop sustained drug delivery system. The solvent evaporation method is a suitable technique for the preparation of Acrycoat S100 microspheres for controlling the release of Ketoprofen for a prolonged duration.

  4. ACECLOFENAC FLOATING TABLETS - A PROMISING SUSTAINED RELEASE DOSAGE FORM

    Directory of Open Access Journals (Sweden)

    Ambati Brahma reddy

    2011-06-01

    Full Text Available The purpose of the present study was to develop an optimized gastric floating drug delivery system (GFDDS containing Aceclofenac as a model drug by using various proportion of polymers such as HPMC E5M and Eudragit RS 100. This was employed to enhance the bioavailability and therapeutic efficacy of the drug. The sustained release formulations of aceclofenac using hydrophobic and hydrophilic polymers were prepared by direct compression method. Optimization of formulation was done by studying effect of drug to polymer ratio on drug release. FT- IR studies indicated absence of any interaction between aceclofenac, polymer (Eudragit RS 100, HPMCE5M and excipients. Five formulations were prepared and formulation A5 possessed good floating property with total floating time between 8-10 hours. The tablets were also evaluated for its hardness, friability and other In- vitro evaluation tests. All parameters complied with IP limits. Results of this study indicated that the combinations of hydrophilic polymers with hydrophobic polymers are suitable to optimize sustained release formulation of aceclofenac.

  5. FORMULATION AND EVALUATION OF SUSTAINED RELEASE PELLETS OF TRAMADOL HYDROCHLORIDE

    Directory of Open Access Journals (Sweden)

    Baskara Haripriya

    2013-02-01

    Full Text Available The aim of the present research is to develop and evaluate a better sustained release multiple unit pellets (MUP formulation of Tramadol hydrochloride. Dissolution and diffusion controlled systems have classically been of primary importance in oral delivery of medication because of their relative ease of production and cost compared with other methods of sustained or controlled delivery. Most of these systems are solids, although a few liquids and suspension have been recently introduced. The present work aimed at developing SR pellets of Tramadol HCl by Wurster process. FTIR studies showed no unacceptable extra peaks which confirm the absence of chemical interaction between the drug and polymer. Angle of repose, tapped density, bulk density values for the formulations were within the range which indicates that pellets prepared by Wurster process were satisfactory for further studies. The percentage drug content of Tramadol was determined by extraction with methanol and analyzed by using UV-visible spectrophotometer at 271nm.

  6. Subconjunctival sustained release 5-fluorouracil for glaucoma filtration surgery

    Institute of Scientific and Technical Information of China (English)

    Li-jun CUI; Nai-xue SUN; Xing-hua LI; Jie HUANG; Jian-gang YANG

    2008-01-01

    Aim:To determine the release characteristics of a 5-fluorouracil-loaded poly (lactic acid) disc (5-FU-PLA-DS) and the effect of sustained drug delivery on the success of glaucoma filtration surgery in rabbit eyes. Methods: A method of microspheres accumulated by excessive carriers was used in the preparation of the 5-FU-PLA-DS. The disc was characterized for drug loading, entrapment efficiency, in vitro release, and external morphology. It was then implanted sub-conjunctivally into rabbit eyes with trabeculectomy. Intraocular pressure, ocular inflammatory reaction, filtration bleb appearance, and persistence were evalu-ated up to postoperative d 90. A quantitative analysis of 5-fluorouracil (5-FU) was performed in the aqueous humor. Ultrasound biomicroscopy was used to assess the appearance of the filtering fistula. Results: The 5-FU-PLA-DS was produced with the drug-loading of 3.07±0.08 mg (mean±SD). 5-FU was released for 91 d with suppressive concentrations. The decrease in intraocular pressure from baseline was significantly more marked in the 5-FU-PLA-DS-implanted eyes during postoperative d 3-90, and the persistence of bleb and filtration fistula was longer than the control eyes (P<0.05). Corneal toxicity and hyperemia triggered by 5-FU was lower in the 5-FU-PLA-DS-implanted eyes than those exposed to 5-FU intraoperatively. The 5-FU concentration in the aqueous humor was insufficient for corneal endothelial damage. No evidence of toxic reaction was found in the conjunctival biopsy. Conclusion: 5-FU-PLA-DS displaying sustained intraocular release of 5-FU, reduced intraocular pres-sure, and prolonged bleb persistence, while significantly reducing 5-FU toxicity.

  7. Effect of hydroxypropyl methylcellulose and hydrogenated castor oil on naproxen release from sustained-release tablets.

    Science.gov (United States)

    Amaral, M H; Lobo, J M; Ferreira, D C

    2001-04-09

    The effect of the concentration of hydrophilic (hydroxypropyl methylcellulose [HPMC]) and hydrophobic (hydrogenated castor oil [HCO]) products, fillers (lactose and dibasic calcium phosphate), and buffers (sodium bicarbonate, calcium carbonate, and sodium citrate) on naproxen release rate was studied. Matrix tablets were prepared by double compression, and in vitro dissolution tests were performed. The dissolution results showed that an increased amount of HPMC or hydrogenated castor oil resulted in reduced drug release. The inclusion of buffers in the HPMC matrix tablets enhanced naproxen release. For HCO tablets, only sodium bicarbonate enhanced naproxen release. The presence of lactose on HPMC matrix tablets did not show a significantly different result from that obtained with the formulation containing dibasic calcium phosphate as a filler. However, for the tablets containing HCO, the presence of lactose significantly enhanced the naproxen release rate. The matrix-forming materials in this study were suitable for use in sustained-release tablets containing naproxen. The drug release can be modulated by adding suitable amounts of diluents and buffers.

  8. Sustained Release of Antibacterial Agents from Doped Halloysite Nanotubes

    Directory of Open Access Journals (Sweden)

    Shraddha Patel

    2015-12-01

    Full Text Available The use of nanomaterials for improving drug delivery methods has been shown to be advantageous technically and viable economically. This study employed the use of halloysite nanotubes (HNTs as nanocontainers, as well as enhancers of structural integrity in electrospun poly-e-caprolactone (PCL scaffolds. HNTs were loaded with amoxicillin, Brilliant Green, chlorhexidine, doxycycline, gentamicin sulfate, iodine, and potassium calvulanate and release profiles assessed. Selected doped halloysite nanotubes (containing either Brilliant Green, amoxicillin and potassium calvulanate were then mixed with poly-e-caprolactone (PLC using the electrospinning method and woven into random and oriented-fibered nanocomposite mats. The rate of drug release from HNTs, HNTs/PCL nanocomposites, and their effect on inhibiting bacterial growth was investigated. Release profiles from nanocomposite mats showed a pattern of sustained release for all bacterial agents. Nanocomposites were able to inhibit bacterial growth for up to one-month with only a slight decrease in bacterial growth inhibition. We propose that halloysite doped nanotubes have the potential for use in a variety of medical applications including sutures and surgical dressings, without compromising material properties.

  9. PREPARATION AND EVALUATION OF SUSTAINED RELEASE MICROSPHERE OF NORFLOXACIN USING SODIUM ALGINATE

    Directory of Open Access Journals (Sweden)

    Raja Chakraverty

    2012-01-01

    Full Text Available Oral controlled drug delivery systems represent the most popular form of sustained drug delivery systems for the obvious advantages of oral route of drug administration. Such systems release the drug with constant or variable release rates. The oral controlled release systems shows a typical pattern of drug release in which the drug concentration is maintained in the therapeutic window for a prolonged period of time (sustained release, thereby ensuring sustained therapeutic action. They are used as single dosage form. Present work involves preparation and evaluation of sustained release of microspheres of Norfloxacin employing sodium alginate as natural polymer. The technique employed for microencapsulation of the drug is ionotropic gelation.

  10. Metformin HCl loaded mucoadhesive agar microspheres for sustained release

    Directory of Open Access Journals (Sweden)

    Khokan Bera

    2013-01-01

    Full Text Available In the recent past, a major interest in the control of blood sugar had been targeted to develop plenty of new formulations. The present work aims at the development of a low cost sustained release system of metformin hydrochloride embedded in microspheres of agar (Gelidium cartilagineum to overcome the frequent dosing of the drug. Models were developed with respect to controlling variables (X 1 , drug: Polymer, X 2 , surfactant concentration, and X 3 , pH of phosphate buffer. The most effective levels of parameters were found as X 1 (1 : 2, X 2 (1.25%, X 3 (phosphate buffer pH 7.4. Instrumental analysis (Fourier transforms infra-red spectroscopy, differential scanning calorimetry, X-ray diffraction and scanning electron microscopy, mucoadhesion study, toxicity test and in vivo study were performed with the optimized product. The best batch (A2 exhibited a high drug entrapment efficiency of 84.82 ± 1.23%, swelling index of 3.84 ± 0.38 and 86% of mucoadhesion after 12 h. The in vitro release was also sustained for more than 12 h.

  11. Optimization of propranolol HCl release kinetics from press coated sustained release tablets.

    Science.gov (United States)

    Ali, Adel Ahmed; Ali, Ahmed Mahmoud

    2013-01-01

    Press-coated sustained release tablets offer a valuable, cheap and easy manufacture alternative to the highly expensive, multi-step manufacture and filling of coated beads. In this study, propranolol HCl press-coated tablets were prepared using hydroxylpropylmethylcellulose (HPMC) as tablet coating material together with carbopol 971P and compressol as release modifiers. The prepared formulations were optimized for zero-order release using artificial neural network program (INForm, Intelligensys Ltd, North Yorkshire, UK). Typical zero-order release kinetics with extended release profile for more than 12 h was obtained. The most important variables considered by the program in optimizing formulations were type and proportion of polymer mixture in the coat layer and distribution ratio of drug between core and coat. The key elements found were; incorporation of 31-38 % of the drug in the coat, fixing the amount of polymer in coat to be not less than 50 % of coat layer. Optimum zero-order release kinetics (linear regression r2 = 0.997 and Peppas model n value > 0.80) were obtained when 2.5-10 % carbopol and 25-42.5% compressol were incorporated into the 50 % HPMC coat layer.

  12. Imprinted Contact Lenses for Sustained Release of Polymyxin B and Related Antimicrobial Peptides.

    Science.gov (United States)

    Malakooti, Negin; Alexander, Cameron; Alvarez-Lorenzo, Carmen

    2015-10-01

    The aim of this work was to develop drug-soft contact lens combination products suitable for controlled release of antimicrobial peptides on the ocular surface. Incorporation of functional monomers and the application of molecular imprinting techniques were explored to endow 2-hydroxyethyl methacrylate (HEMA) hydrogels with the ability to load and to sustain the release of polymyxin B and vancomycin. Various HEMA-drug-functional monomer-cross-linker molar ratios were evaluated to prepare polymyxin B imprinted and non-imprinted hydrogels. Acrylic acid-functionalized and imprinted hydrogels loaded greater amounts of polymyxin B and led to more sustained release profiles, in comparison with non-functionalized and non-imprinted networks. Polymyxin B-loaded hydrogels showed good biocompatibility in hen's egg test-chorioallantoic membrane tests. Functionalized hydrogels also loaded vancomycin and sustained its release, but the imprinting effect was only exhibited with polymyxin B, as demonstrated in rebinding tests. Microbiological assays carried out with Pseudomonas aeruginosa allowed identification of the most suitable hydrogel composition for efficient bacteria eradication; some hydrogels being able to stand several continued challenges against this important bacterial pathogen.

  13. Preparation and in vitro release performance of sustained-release captopril/Chitosan-gelatin net-polymer microspheres

    Science.gov (United States)

    Zhou, Li; Xu, Junming; Song, Yimin; Gao, Yuanyuan; Chen, Xiguang

    2007-07-01

    The captopril/Chitosan-gelatin net-polymer microspheres (CTP/CGNPMs) were prepared using Chitosan (CTS) and gelatin (GT) by the methods of emulsification, cross-linked reagent alone or in combination and microcrystalline cellulose (MCC) added in the process of preparation of microspheres, which aimed to eliminate dose dumping and burst phenomenon of microspheres for the improvement of the therapeutic efficiency and the decrease of the side effects of captopril (CTP). The results indicated that CTP/CGNPMs had a spherical shape, smooth surface and integral structure inside but no adhesive phenomena in the preparation. The size distribution ranged from 220 μm to 280 μm. The CTP release test in vitro demonstrated that CTP/CGNPMs played the role of retarding the release of CTP compared with ordinary CTP tablets. The release behaviors of CGNPMS were influenced by preparation conditions such as experimental material ratio (EMR) and composition of cross linking reagents. Among these factors, the EMR (1/4), CLR (FA+SPP) and 0.75% microcrystalline cellulose (MCC) added to the microspheres constituted the optimal scheme for the preparation of CTP/CGNPMs. The ER, DL and SR of CTP/CGNPMs prepared according to the optimal scheme were 46.23±4.51%, 9.95±0.77% and 261±42%, respectively. The CTP/CGNPMs had the good characteristics of sustained release of drug and the process of emulsification and cross-linking were simple and stable. The CGNPMs are likely to be an ideal sustained release formulation for water-soluble drugs.

  14. Preparation and in vitro Release Performance of Sustained-release Captopril/Chitosan-gelatin Net-polymer Microspheres

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    The captopril/Chitosan-gelatin net-polymer microspheres (CTP/CGNPMs) were prepared using Chitosan (CTS) and gelatin (GT) by the methods of emulsification, cross-linked reagent alone or in combination and microcrystalline cellulose (MCC) added in the process of preparation of microspheres, which aimed to eliminate dose dumping and burst phenomenon of microspheres for the improvement of the therapeutic efficiency and the decrease of the side effects of captopril (CTP). The results indicated that CTP/CGNPMs had a spherical shape, smooth surface and integral structure inside but no adhesive phenomena in the preparation. The size distribution ranged from 220 μm to 280 μm. The CTP release test in vitro demonstrated that CTP/CGNPMs played the role of retarding the release of CTP compared with ordinary CTP tablets. The release behaviors of CGNPMS were influenced by preparation conditions such as experimental material ratio (EMR) and composition of cross linking reagents. Among these factors, the EMR (1/4), CLR (FA+SPP) and 0.75% microcrystalline cellulose (MCC) added to the microspheres constituted the optimal scheme for the preparation of CTP/CGNPMs. The ER, DL and SR of CTP/CGNPMs prepared according to the optimal scheme were 46.23±4.51%, 9.95±0.77% and 261±42%, respectively. The CTP/CGNPMs had the good characteristics of sustained release of drug and the process of emulsification and cross-linking were simple and stable. The CGNPMs are likely to be an ideal sustained release formulation for water-soluble drugs.

  15. Challenges to antagonist blockade during sustained-release naltrexone treatment.

    Science.gov (United States)

    Kunøe, Nikolaj; Lobmaier, Philipp; Vederhus, John Kåre; Hjerkinn, Bjørg; Gossop, Michael; Hegstad, Solfrid; Kristensen, Øistein; Waal, Helge

    2010-09-01

    Naltrexone is a competitive opioid antagonist that effectively blocks the action of heroin and other opioid agonists. Sustained-release naltrexone formulations are now available that provide long-acting opioid blockade. This study investigates the use of heroin and other opioids among opioid-dependent patients receiving treatment with long-acting naltrexone implants, their subjective experience of drug 'high' after opioid use, and factors associated with opioid use. Participants (n = 60) were opioid-dependent patients receiving treatment with naltrexone implants. Outcome data on substance use, drug 'high', depression and criminal activity were collected over a 6-month period. Blood samples were taken to monitor naltrexone plasma levels, and hair samples to verify self-reported opioid use. More than half [n = 34 or 56%; 95% confidence interval (CI) 44-68%)] the patients challenged the blockade with illicit opioids during the 6-month treatment period; 44% (n = 26; 95% CI 32-56%) were abstinent from opioids. Mean opioid use was reduced from 18 [standard deviation (SD)13] days during the month preceding treatment to 6 days (SD 11) after 6 months. Of the respondents questioned on opioid 'high' (n = 31), nine patients (30%; 95% CI 16-47%) reported partial drug 'high' following illicit opioid use, and three (12%; 95% CI 3-26%) reported full 'high'. Opioid use was associated with use of non-opioid drugs and criminal behaviour. Challenging naltrexone blockade with heroin on at least one occasion is common among sustained-release naltrexone patients, but only a minority of patients use opioids regularly. Challenges represent a warning sign for poor outcomes and often occur in the context of polydrug use and social adjustment problems.

  16. PARTITION-OPTIMIZED SINGLE EMULSION PARTICLES IMPROVE SUSTAINED RELEASE OF AMPHIPHILIC BUMPED KINASE INHIBITORS TO CONTROL MALARIA TRANSMISSION

    Directory of Open Access Journals (Sweden)

    Christina Yacoob

    2015-11-01

    Full Text Available Amphiphilic molecules are challenging to be incorporatedinto polymeric particles for sustained release due to their significant solubility in both water and organic solvent used in the fabrication process. Here, we investigated an extensive panel of fabrication methods for the incorporation and release of amphiphilic molecules, in particular, novel amphiphilic bumped kinase inhibitors (BKIs. Previously, BKIswere shown to reduce malaria transmission by blocking of gametocyte exflagellation. Prolonged BKI bioavailability for effective transmission blocking is crucial since infectious gametocytes circulate for several weeks inthe mammalian host, well beyond the half-life of BKIs. So far, delivery systems for sustained release of those BKIs have not been successfully formulated yet. Here we demonstrate that out of several delivery vehicles the partition-optimized single emulsion particles are the ideal system for incorporation and sustained release of amphiphilic BKIs. They increased the incorporation greater than 90% through optimized partitioning of amphiphilic molecules to the polymer phase and sustained release of BKIs up to several weeks with a reduction in the initial burst release. Overall this work provides a method for the incorporation and sustained release of amphiphilic BKIs, and can be adapted for other amphiphilic molecules.

  17. 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.

  18. Entrapment and Sustained Release of Hydrophobic Drugs with Different Molecular Weights from PHBHHx-PEG Nanoparticles

    Institute of Scientific and Technical Information of China (English)

    FAN Fan; LU Xiao-yun; REN Kai; MA Jian-gang

    2014-01-01

    Biodegradable polymeric nanoparticles are more and more frequently used in drug delivery systems, which represent one of the most rapidly developing areas. In our previous study, a novel natural hybrid polyester, polyethylene glycol 200 (PEG200) end-capped poly (3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx-PEG) was directly produced by Aeromonas hydrophila fermentation. In this study, the performance of the novel biodegradable PHBHHx-PEG copolyester as a sustained release carrier for hydrophobic drugs with different molecular weights and the in vitro sustained release profile were investigated. 5-Fluorouracil (5-Fu, Mw=130.1), TGX221 (Mw=364.4), and Rapamycin (RAP, Mw=914.2) were used as the model drugs. PHBHHx-PEG nanoparticles entrapped with 5-Fu, TGX221 and RAP were fabricated by a modified emulsification/solvent evaporation method, respectively. The average diameter of 5-Fu, TGX221, and RAP loaded PHBHHx-PEG nanoparticles was between 198.2-217.4 nm, and the entrapment efficiency of the three drugs was 62.5%, 93.4% and 91.9%, respectively. The in vitro release profiles of 5-Fu, TGX221 and RAP from PHBHHx-PEG nanoparticles were different. 5-Fu showed faster release rate and an obvious initial burst release phase. TGX221 and RAP were demonstrated to be released more slowly and steadily. The release percentages of 5-Fu, TGX221 and RAP were 97.7%, 85.1%and 74.7%after releasing for 72 h. PHBHHx-PEG is a kind of promising material as a carrier for the entrapment and delivery of hydrophobic drugs especially for those drugs with high molecular weight.

  19. A multiple-dose study of sustained-release theophylline and aminophylline.

    Science.gov (United States)

    Meyer, M C; Straughn, A B; Lieberman, P

    1980-08-01

    This study evaluated the relative bioavailability of a sustained-release capsule of theophylline, an elixir of theophylline, and a sustained-release tablet of aminophylline. Twelve healthy, nonsmoking, adult male subjects received nine doses of each of the three products in a crossover study conducted over a ten-day period. Each dosage form contained approximately 250 mg of theophylline and was administered every eight hours. Concentrations of theophylline in the plasma at steady state demonstrated the equivalence of the three dosage forms in terms of the percent of drug absorbed, including the tablet which had exhibited reduced bioavailability in an earlier single-dose study of only five subjects. The steady-state average concentrations of theopylline in the plasma were 9.8 micrograms/ml, 10.3 micrograms/ml and 10.8 micrograms/ml for the tablet, capsulse, and elixir, respectively. The areas under the curves of the plasma level vs time for the three dosage forms were within 9 percent of each other. These data indicate that a significant reduction in fluctuations of the plasma level of theophylline was achieved with the two sustained-release dosage forms, compared to the elixir.

  20. 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.

  1. Novel Sustained-Release of Propafenone through Pellets: Preparation and in Vitro/in Vivo Evaluation

    OpenAIRE

    2014-01-01

    In this study, an extrusion-spheronization method was applied successfully to fabricate propafenone hydrochloride (PPF) sustained-release pellets. Using scanning electron microscopy, it was shown that the PPF pellets had a mean size of approximately 950 µm with a spherical shape. The in vitro release profiles indicated that the release of PPF from the pellets exhibited a sustained release behavior. The relatively high correlation coefficient (r) values obtained from the analysis of the amount...

  2. Monitoring and Evaluation of Environmental Flow Prescriptions for Five Demonstration Sites of the Sustainable Rivers Project

    Science.gov (United States)

    Konrad, Christopher P.

    2010-01-01

    The Nature Conservancy has been working with U.S. Army Corps of Engineers (Corps) through the Sustainable Rivers Project (SRP) to modify operations of dams to achieve ecological objectives in addition to meeting the authorized purposes of the dams. Modifications to dam operations are specified in terms of environmental flow prescriptions that quantify the magnitude, duration, frequency, and seasonal timing of releases to achieve specific ecological outcomes. Outcomes of environmental flow prescriptions implemented from 2002 to 2008 have been monitored and evaluated at demonstration sites in five rivers: Green River, Kentucky; Savannah River, Georgia/South Carolina; Bill Williams River, Arizona; Big Cypress Creek, Texas; and Middle Fork Willamette River, Oregon. Monitoring and evaluation have been accomplished through collaborative partnerships of federal and state agencies, universities, and nongovernmental organizations.

  3. FORMULATION AND EVALUATION OF TIZANIDINE SUSTAINED RELEASE MATRIX TABLETS USING HYDROXY PROPYL METHY CELLULOSE

    Directory of Open Access Journals (Sweden)

    Ankita Srivastava et al

    2012-09-01

    Full Text Available Tizanidine is a muscle relaxant agent, with the half life of 2.5 hours and requires daily doses to maintain adequate plasma concentrations. The present study was undertaken to with an aim to formulation development and evaluation of Tizanidine hydrochloride sustained release tablets using hydrophilic polymer to sustain the action of Tizanidine. Different batches of Tizanidine hydrochloride were prepared based on preformulation studies using HPMC K100M HPMC K4M and HPMC K100 having different viscosities to calculate the sustained release properties. Tizanidine hydrochloride was analysed by using HPLC using wavelength 240 nm. Results of in-vitro study indicate that the trial formulation 5 having considerable sustaining property. From the discussion it is concluded that the trial formulation 5 had considerable in-vitro drug release. Trial formulation 5 can be taken as an ideal or optimized formulation of sustained release tablets for 12 hours release and it fulfils all the requirements for sustained.

  4. Improved sustained release of antigen from immunostimulatory DNA hydrogel by electrostatic interaction with chitosan.

    Science.gov (United States)

    Ishii-Mizuno, Yumiko; Umeki, Yuka; Onuki, Yoshinori; Watanabe, Hiroshi; Takahashi, Yuki; Takakura, Yoshinobu; Nishikawa, Makiya

    2017-01-10

    Immunostimulatory DNA hydrogel (sDNA hydrogel) containing unmethylated cytosine-phosphate-guanine (CpG) sequences has been demonstrated to be a useful antigen delivery system, which can effectively induce an antigen-specific immune response through stimulation of the innate immune system. However, relatively rapid release of antigens from the sDNA hydrogel limits its potential. To enhance the potency of the sDNA hydrogel via improvement of its sustained release property, we selected chitosan, a biocompatible cationic polymer which electrostatically interacts with DNA, and mixed it with the sDNA hydrogel. Compared to unmixed sDNA hydrogel, sDNA hydrogel mixed with chitosan (Chitosan-sDNA hydrogel) was more stable, tougher, had more bound water, released a model antigen ovalbumin (OVA) more slowly in vitro, and provided longer retention of OVA at the injection site after intradermal injection into mice. Intradermal immunization of mice with the OVA-loaded Chitosan-sDNA hydrogel resulted in the induction of a higher level of OVA-specific IgG in serum compared with OVA-loaded sDNA hydrogel with no chitosan. These results indicate that the Chitosan-sDNA hydrogel is an improved sustained release formulation for efficient induction of antigen-specific immune responses. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Development of sustained antimicrobial-release systems using poly(2-hydroxyethyl methacrylate)/trimethylolpropane trimethacrylate hydrogels.

    Science.gov (United States)

    Kitagawa, Haruaki; Takeda, Kahoru; Kitagawa, Ranna; Izutani, Naomi; Miki, Saeki; Hirose, Nanako; Hayashi, Mikako; Imazato, Satoshi

    2014-10-01

    Reconstructive materials with sustained antimicrobial effects could be useful for preventing infectious diseases in an environment containing indigenous bacteria or fungi such as the oral cavity. With the objective of applying a non-biodegradable hydrogel to resin-based materials as a reservoir for water-soluble antimicrobials, novel hydrogels consisting of 2-hydroxyethyl methacrylate (HEMA) and trimethylolpropane trimethacrylate (TMPT) were fabricated. Cetylpyridinium chloride (CPC) was loaded into five hydrogels comprising different ratios of HEMA/TMPT, and their ability to release as well as to be recharged with CPC was examined in vitro. A polyHEMA/TMPT hydrogel comprising 50% HEMA/50% TMPT could be effectively loaded and recharged with CPC by immersion into a CPC solution, demonstrating the longest release of CPC, above the concentration required to inhibit bacteria and fungi. The binding of CPC to the hydrogels was mainly through hydrophobic interaction. Loading of CPC into a hydrogel by mixing CPC powder with the HEMA/TMPT monomer before polymerization resulted in marked extension of the initial CPC-release period. The CPC-pre-mixed hydrogel was confirmed to exhibit antibacterial activity by agar diffusion tests. It is possible to achieve a sustained release system for antimicrobials by pre-mix loading and recharging CPC into a 50% HEMA/50% TMPT hydrogel.

  6. Preparation of sustained release co-extrudates by hot-melt extrusion and mathematical modelling of in vitro/in vivo drug release profiles.

    Science.gov (United States)

    Quintavalle, U; Voinovich, D; Perissutti, B; Serdoz, F; Grassi, G; Dal Col, A; Grassi, M

    2008-03-01

    Aim of this work was to develop a cylindrical co-extrudate characterised by an in vivo sustained release profile by means of a hot-melt extrusion process. Co-extrudate was made up of two concentric extruded matrices: an inner one having a hydrophilic character, based on polyethylene glycol, and an outer one with lipophilic character, based on microcrystalline wax. Both segments contained theophylline as a model drug. A screening between several devices differing for dimensions (diameter and length) and relative proportions of the inner and outer part was carried out on the basis of their in vitro drug release and the release mechanism was studied by means of a mathematical model. The co-extrudate exhibiting the desired sustained release was selected for in vivo bioavailability studies. In vivo studies confirmed the achievement of the purpose of the research, demonstrating the desired release of theophylline on four healthy volunteers. Accordingly, hot-melt extrusion process is a viable method to produce in a single step co-extrudates showing a sustained release. In addition, the developed mathematical model proved to be a reliable descriptor of the both in vitro and in vivo experimental data.

  7. Near-Term Demonstration of Benign, Sustainable, Nuclear Power

    Energy Technology Data Exchange (ETDEWEB)

    Walter, C.E.

    2000-09-21

    Nuclear power reactors have been studied, researched, developed, constructed, demonstrated, deployed, operated, reviewed, discussed, praised and maligned in the United States for over half a century. These activities now transcend our national borders and nuclear power reactors are in commercial use by many nations. Throughout the world, many have been built, some have been shut down, and new ones are coming on line. Almost one-fifth of the world's electricity in 1997 was produced from these reactors. Nuclear power is no longer an unknown new technology. A large increase in world electricity demand is projected for the coming century. In lieu of endless research programs on ''new'' concepts, it is now time to proceed vigorously with widespread deployment of the best nuclear power option for which most parameters are already established. Here, we develop an aggressive approach for initiating the deployment of such a system--with the potential to produce over half of the world's electricity by mid-century, and to continue at that level for several centuries.

  8. Sustainability Logistics Basing - Science and Technology Objective - Demonstration; Industry Assessment and Demonstration Final Report

    Science.gov (United States)

    2017-08-14

    response to this notice that is marked Proprietary will be handled accordingly. Responses may not include Classified material. Responses to this notice...following minimum entrance criteria (initial): -TRL level and justification: Documented demonstration including bench test results that the

  9. 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

  10. 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.

  11. Optimized loading and sustained release of hydrophilic proteins from internally nanostructured particles.

    Science.gov (United States)

    Chemelli, Angela; Maurer, Manuela; Geier, Roman; Glatter, Otto

    2012-12-11

    In this study, we demonstrate that emulsified microemulsions and micellar cubosomes are suitable as sustained delivery vehicles for water-soluble proteins. Through structural modifications, the loading efficiency of two model proteins, namely bovine serum albumin (BSA) and cytochrome c could be remarkably increased. A procedure for preparing these particles loaded with optimized amounts of sensitive substances is presented. Loading and dispersion at low temperatures is performed in two successive steps. First, a water-in-oil microemulsion is loaded with the proteins. Subsequently, this phase is dispersed in water resulting in particles with microemulsion and micellar cubic internal structure and a size of approximately 620 nm. This two-step method ensures optimal loading of the particles with the proteins. These nanostructured particles are able to sustain the release of the water-soluble BSA and cytochrome c. Within one day, less than 10% of BSA and 15% of cytochrome c are released. The release rate of cytochrome c is influenced by the nanostructure of the particles.

  12. Hot Melt Extrusion for Sustained Protein Release: Matrix Erosion and In Vitro Release of PLGA-Based Implants.

    Science.gov (United States)

    Cossé, Anne; König, Corinna; Lamprecht, Alf; Wagner, Karl G

    2017-01-01

    The design of biodegradable implants for sustained release of proteins is a complex challenge optimizing protein polymer interaction in combination with a mini-scale process which is predictive for production. The process of hot melt extrusion (HME) was therefore conducted on 5- and 9-mm mini-scale twin screw extruders. Poly(lactic-co-glycolic acid) (PLGA) implants were characterized for their erosion properties and the in vitro release of the embedded protein (bovine serum albumin, BSA). The release of acidic monomers as well as other parameters (pH value, mass loss) during 16 weeks indicated a delayed onset of matrix erosion in week 3. BSA-loaded implants released 17.0% glycolic and 5.9% lactic acid after a 2-week lag time. Following a low burst release (3.7% BSA), sustained protein release started in week 4. Storage under stress conditions (30°C, 75% rH) revealed a shift of erosion onset of 1 week (BSA-loaded implants: 26.9% glycolic and 9.3% lactic acid). Coherent with the changed erosion profiles, an influence on the protein release was observed. Confocal laser scanning and Raman microscopy showed a homogenous protein distribution throughout the matrix after extrusion and during release studies. Raman spectra indicated a conformational change of the protein structure which could be one reason for incomplete protein release. The study underlined the suitability of the HME process to obtain a solid dispersion of protein inside a polymeric matrix providing sustained protein release. However, the incomplete protein release and the impact by storage conditions require thorough characterization and understanding of erosion and release mechanisms.

  13. Sustained release of small molecules from carbon nanotube-reinforced monetite calcium phosphate cement.

    Science.gov (United States)

    Lin, Boren; Zhou, Huan; Leaman, Douglas W; Goel, Vijay K; Agarwal, Anand K; Bhaduri, Sarit B

    2014-10-01

    The interest in developing calcium phosphate cement (CPC) as a drug delivery system has risen because of its capability to achieve local and controlled treatment to the site of the bone disease. The purpose of this study was to investigate the release pattern of drug-carrying carboxylic acid-functionalized multi-walled carbon nanotube (MWCNT)-reinforced monetite (DCPA, CaHPO4)-based CPC. Z-Leu-Leu-Leu-al (MG132), a small peptide molecule inhibiting NF-κB-mediated osteoclastic resorption, was used as a model drug. MG132 was added into the cement during setting and released into the medium used to culture indicator cells. Significant cell death was observed in osteoblast MC3T3-E1 cells cultured in the medium incubated with MG132-loaded CPC; however, with the presence of MWCNTs in the cement, the toxic effect was not detectable. NF-κB activation was quantified using a NF-κB promoter-driving luciferase reporter in human embryonic kidney 293 cells. The medium collected after incubation with drug-incorporated CPC with or without MWCNT inhibited TNFα-induced NF-κB activation indicating that the effective amount of MG132 was released. CPC/drug complex showed a rapid release within 24h whereas incorporation of MWCNTs attenuated this burst release effect. In addition, suppression of TNFα-induced osteoclast differentiation in RAW 264.7 cell culture also confirmed the sustained release of MWCNT/CPC/drug. Our data demonstrated the drug delivery capability of this cement composite, which can potentially be used to carry therapeutic molecules to improve bone regeneration in conjunction with its fracture stabilizing function. Furthermore, it suggested a novel approach to lessen the burst release effect of the CPC-based drug delivery system by incorporating functionalized MWCNTs.

  14. 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.

  15. Nanomedicine for glaucoma: liposomes provide sustained release of latanoprost in the eye

    Directory of Open Access Journals (Sweden)

    Natarajan JV

    2012-01-01

    Full Text Available Jayaganesh V Natarajan1*, Marcus Ang2*, Anastasia Darwitan1, Sujay Chattopadhyay3, Tina T Wong2, Subbu S Venkatraman1 1Materials Science and Engineering, Nanyang Technological University, Singapore; 2Singapore Eye Research Institute, Singapore; 3Polymer Division, Indian Institute of Technology Roorkee, India*These authors contributed equally to this workPurpose: To report the development and therapeutic evaluation of a liposomal nanocarrier for sustained release of latanoprost, in the rabbit eye.Methods: We fabricated latanoprost-loaded egg-phosphatidylcholine (EggPC liposomes using the film hydration technique. The delivery vehicles were nano-sized (Z avg = 109 ± 18 nm, had a narrow poly dispersity index (PDI = 0.19 ± 0.04, and a very high loading efficiency (94% ± 5%. Based on in vitro data, we evaluated this formulation for lowering intraocular pressure (IOP in rabbit eyes. Following a single subconjunctival injection of the latanoprost loaded formulation, the eyes were clinically monitored and the IOP recorded.Results: Latanoprost-loaded EggPC liposomes demonstrated a high drug/lipid mole ratio of 0.181, remained stable for at least 6 months on storage (4°C, and at least 1 month at 25°C. A slow and sustained release of 60% of latanoprost was achieved by 14 days in the in vitro release study. The same formulation demonstrated a greater sustained IOP lowering effect compared with daily administration of topical latanoprost beyond 90 days (4.8 ± 1.5 vs 2.5 ± 0.9 mmHg; P < 0.001. No signs of inflammation were evident in the eyes from slit-lamp examination analysis.Conclusion: The loading required for a long-term sustained delivery of latanoprost for up to 90 days in the rabbit eyes was achieved with EggPC liposomes. A single injection of latanoprost-loaded EggPC liposomes can lower the IOP for up to 90 days, with a greater IOP lowering effect than daily topical administration of latanoprost.Keywords: nanomedicine, nanoliposomes, Egg

  16. [Sustained-release progesterone vaginal suppositories 3-development and clinical feasibility testing].

    Science.gov (United States)

    Nakayama, Ayako; Yamaguchi, Naho; Ohno, Yukiko; Miyata, Chihiro; Kondo, Haruomi; Sunada, Hisakazu; Okamoto, Hirokazu

    2013-01-01

      Although progesterone vaginal suppositories (hospital-formulated) are used for the treatment of infertility, their half-life is so short that multiple doses are required. In this study, we aimed to develop sustained-release vaginal suppositories suitable for clinical use which maintain an effective blood concentration by once-a-day treatment, and prepared 7 types of suppository containing the sustained-release progesterone tablets to characterize their sustained-release performance. We selected one candidate suppository among them, taking recovery rate, reproducibility, and hardness, as well as the sustained-release performance into consideration. The shell of the selected suppository is composed of VOSCO S-55 and progesterone for rapid release. The molded progesterone tablets for sustained release were embedded inside. The distribution of the weight and content of the suppository was limited, and the release rate of progesterone was significantly slower than that of a conventional progesterone suppository prepared in our hospital. The single-dose administration of the selected suppository to five healthy volunteers led to significant extension of the blood concentration. We also confirmed the rise of the basic value by multiple administration. The simulation comparison suggested that the blood progesterone concentration is controlled by once-a-day administration of the selected suppository better than twice-a-day administration of the conventional suppository. In conclusion, the sustained-release vaginal suppository prepared in this study was considered to be useful for clinical treatment.

  17. 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.

  18. 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.

    2010-01-01

    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. PMID:19631376

  19. 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.

  20. The Role of Trials and Demonstration Projects in the Development of a Sustainable Bioeconomy

    Directory of Open Access Journals (Sweden)

    Arne Martin Fevolden

    2017-03-01

    Full Text Available This article provides an overview of the literature on demonstration projects and trials, and accounts for how insights drawn from this literature can contribute to the development of a sustainable bioeconomy. The article reviews the literature on demonstration projects and trials, covering both more broad-based studies on demonstration projects mainly carried out in the US and more specific studies on demonstration projects for energy technologies carried out in Europe, the US, and Japan. The aim of the article is to account for how demonstration projects and trials can contribute to the development of a sustainable bioeconomy.

  1. Biocompatible reverse thermal gel sustains the release of intravitreal bevacizumab in vivo.

    Science.gov (United States)

    Rauck, Britta M; Friberg, Thomas R; Medina Mendez, Carlos A; Park, Daewon; Shah, Veeral; Bilonick, Richard A; Wang, Yadong

    2014-01-23

    We assessed the in vivo release profile of bevacizumab from and biocompatibility of poly(ethylene glycol)-poly-(serinol hexamethylene urethane), or ESHU, a thermoresponsive hydrogel administered intravitreally for drug delivery. The technical feasibility of injection was assessed quantitatively via mechanical testing. For in vivo studies, New Zealand White rabbit eyes were injected intravitreally with 0.05 mL of either: ESHU dissolved in 25 mg/mL bevacizumab, ESHU dissolved in PBS, or 25 mg/mL bevacizumab. Clinical examination included IOP measurements and examination with indirect ophthalmoscopy for signs of inflammation. Additionally, eyes were examined histologically following euthanasia. To quantify bevacizumab release, aqueous humor samples were obtained via anterior chamber paracentesis and ELISA was used to determine the concentration of drug weekly. In vitro cytotoxicity testing also was performed using bovine corneal endothelial cells. The ESHU was injected easily through a 31-gauge needle, was well tolerated in vivo, and caused minimal cell death in vitro when compared to other common materials, such as silicone oil. The long-term presence of the gel did not affect IOP, and there was no evidence of inflammation histologically or through indirect observation. The ESHU sustained the release of bevacizumab for over 9 weeks and maintained a drug concentration that averaged 4.7 times higher than eyes receiving bolus bevacizumab injections. To our knowledge, this is the first report demonstrating sustained bevacizumab release in vivo from an intravitreally injected hydrogel formulation, suggesting that this delivery system may be a promising candidate for ocular drug delivery.

  2. Diatom silica microparticles for sustained release and permeation enhancement following oral delivery of prednisone and mesalamine.

    Science.gov (United States)

    Zhang, Hongbo; Shahbazi, Mohammad-Ali; Mäkilä, Ermei M; da Silva, Tiago H; Reis, Rui L; Salonen, Jarno J; Hirvonen, Jouni T; Santos, Hélder A

    2013-12-01

    Diatoms are porous silica-based materials obtained from single cell photosynthetic algae. Despite low cost, easy purification process, environmentally safe properties, and rapidly increasing potentials for medical applications, the cytotoxicity of diatoms and the effect on drug permeation of oral formulations have not been studied so far. Herein, we have evaluated the potential of diatom silica microparticles (DSMs) for the delivery of mesalamine and prednisone, which are two commonly prescribed drugs for gastrointestinal (GI) diseases. Transmission electron microscopy analysis of the morphological surface changes of Caco-2/HT-29 monolayers and the cell viability data in colon cancer cells (Caco-2, HT-29 and HCT-116) showed very low toxicity of diatoms at concentrations up to 1000 μg/mL. The mesalamine and prednisone release under simulated GI conditions indicated prolonged release of both drugs from the diatoms. Furthermore, drug permeation across Caco-2/HT-29 co-culture monolayers demonstrated that diatoms are capable to enhance the drug permeability. Overall, this study evaluated DSMs' cytotoxicity in colon cancer cells and the effect of DSMs on drug permeability across Caco-2/HT-29 monolayers. Our results demonstrate that DSMs can be considered as a non-cytotoxic biomaterial with high potential to improve the mesalamine and prednisone bioavailability by sustaining the drug release and enhancing drug permeability.

  3. 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....

  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....

  5. Methylprednisolone microsphere sustained-release membrane inhibits scar formation at the site of peripheral nerve lesion

    Institute of Scientific and Technical Information of China (English)

    Qiang Li; Teng Li; Xiang-chang Cao; De-qing Luo; Ke-jian Lian

    2016-01-01

    Corticosteroids are widely used for the treatment of acute central nervous system injury. However, their bioactivity is limited by their short half-life. Sustained release of glucocorticoids can prolong their efifcacy and inhibit scar formation at the site of nerve injury. In the present study, we wrapped the anastomotic ends of the rat sciatic nerve with a methylprednisolone sustained-release membrane. Compared with methylprednisone alone or methylprednisone microspheres, the methylprednisolone microsphere sustained-release membrane reduced tissue adhesion and inhibited scar tissue formation at the site of anastomosis. It also increased sciatic nerve function index and the thick-ness of the myelin sheath. Our ifndings show that the methylprednisolone microsphere sustained-release membrane effectively inhibits scar formation at the site of anastomosis of the peripheral nerve, thereby promoting nerve regeneration.

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

    National Research Council Canada - National Science Library

    Wang, Kai; Chen, Xuejiao; Pan, Yiwa; Cui, Yun; Zhou, Xin; Kong, Deling; Zhao, Qiang

    2015-01-01

    .... 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...

  7. 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 ... Diltiazem HCl is a water soluble calcium-channel ... K15M CR, on contact with dissolution media or ..... Government of India, New Delhi.

  8. Pharmacokinetics of green tea catechins in extract and sustained-release preparations.

    Science.gov (United States)

    Janle, Elsa M; Morré, Dorothy M; Morré, D James; Zhou, Qin; Zhu, Yongxin

    2008-01-01

    Catechins are a major constituent of green tea. For green tea to have cancer therapeutic benefit, catechin concentrations in the range of 100 nM are required continuously until apoptosis (programmed cell death) is induced. To prolong elevated plasma and interstitial concentrations of catechins, a sustained-release formulation of green tea extract was tested and compared to a commercial green tea extract (Tegreen97®). Sustained-release formulations are usually developed in the pharmaceutical industry to slowly deliver the compound over a period of time and increase the dosing interval. Plasma and interstitial fluid (ISF) pharmacokinetics of catechins were determined following an oral dose in the rat. The sustained-release formulation profile included multiple smaller peaks of total catechins in both plasma and ISF. Interstitial fluid profiles of green tea extract indicate that higher catechins concentration and longer duration in tissue than in blood may make a sustained-release form unnecessary.

  9. 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.

  10. 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.

  11. Marbofloxacin-encapsulated microparticles provide sustained drug release for treatment of veterinary diseases.

    Science.gov (United States)

    Lee, Joohyeon; Kwon, Ho Jin; Ji, Hyunggun; Cho, Sun Hang; Cho, Eun-Haeng; Han, Hee Dong; Shin, Byung Cheol

    2016-03-01

    Fluoroquinolone antibiotics with concentration-dependent killing effects and a well-established broad spectrum of activity are used commonly to treat infectious diseases caused by bacteria. However, frequent and excessive administration of these antibiotics is a serious problem, and leads to increased number of drug-resistant bacteria. Thus, there is an urgent need for novel fluoroquinolone antibiotic formulations that minimize the risk of resistance while maximizing their efficacy. In this study, we developed intramuscularly injectable polymeric microparticles (MPs) that encapsulated with marbofloxacin (MAR) and were composed of poly(D,L-lactide-co-glycolic acid) (PLGA) and poloxamer (POL). MAR-encapsulated MP (MAR-MP) had a spherical shape with particle size ranging from 80 μm to 120 μm. Drug loading efficiency varied from 55 to 85% (w/w) at increasing amount of hydrophilic agent, POL. Drug release from MAR-MP demonstrated a significant and sustained increase at increased ratios of POL to PLGA. These results indicate that MAR-MP is an improved drug delivery carrier for fluoroquinolone antibiotics, which can reduce the number of doses needed and sustain a high release rate of MAR for 2-3 days. As a novel and highly effective drug delivery platform, MAR-MP has great potential for use in a broad range of applications for the treatment of various veterinary diseases.

  12. Pharmacokinetics of Green Tea Catechins in Extract and Sustained-Release Preparations

    OpenAIRE

    Janle, Elsa M; Morré, Dorothy M.; Morré, D. James; Zhou, Qin; Zhu, Yongxin

    2008-01-01

    Catechins are a major constituent of green tea. For green tea to have cancer therapeutic benefit, catechin concentrations in the range of 100 nM are required continuously until apoptosis (programmed cell death) is induced. To prolong elevated plasma and interstitial concentrations of catechins, a sustained-release formulation of green tea extract was tested and compared to a commercial green tea extract (Tegreen97®). Sustained-release formulations are usually developed in the pharmaceutical i...

  13. Development and In Vitro Characterization of Sustained Release Pellets of Venlafaxine Hydrochloride

    OpenAIRE

    P.REMYA; N. Damodharan; Dinesh Kumar, S.; V. Sowjanya

    2012-01-01

    The present study was undertaken with development and in-vitro characterization of sustained release pellets of venlafaxine hydrochloride by wruster process technique .which release the drug in sustained manner over a period of 20 hours. The different viscosity grades of polymers are HPMC-E6, Ethyl cellulose 7cps, MCC-101 were preparation of granules or pellets by wurster coating .The granules were prepared and evaluated for Angle of repose, bulk density, tapped density, cars index, moisture ...

  14. In vitro release of theophylline from poly(lactic acid) sustained-release pellets prepared by direct compression.

    Science.gov (United States)

    Kader, A; Jalil, R

    1998-06-01

    Poly(L-lactic acid), (L-PLA) pellets containing theophylline as a model drug were prepared with increasing bovine serum albumin (BSA) load of 10, 20, 30, 40, or 50% by direct compression. The drug release from pellets was studied in phosphate buffered saline (PBS, pH 7.4) at 37 degrees C. The annealing effect on theophylline release from pellets was also studied at 20, 30, 60, and 80 degrees C. In all cases, release kinetics followed the Higuchian mechanism with an initial burst effect followed by sustained release of theophylline during the experimental period. Increasing BSA load resulted in a linear increase in Higuchian release rates presumably because of the hydrophilic nature of BSA. Furthermore, BSA did not interact chemically with the polymer matrix and was held physically by the dense polymer matrix. However, drug release decreased with an increase in annealing temperature. Release of theophylline was higher from PLA-BSA combination pellets compared to PLA pellets at temperatures below the glass transition temperature (Tg) of the polymer and lower for temperatures above Tg. The temperature effect on drug release may be attributed to both the reduction of core solubility in the bulk phase and the lowering of diffusibility of the polymeric membrane. No drug-polymer interactions or polymer degradation was observed within the experimental setup when studied by differential scanning calorimetry (DSC), infrared (FTIR) spectroscopy, and gravimetric methods. DSC studies of pellets showed no hints of microstructural changes (crystallinity) of the polymers. In our experiments, theophylline was released primarily by leaching through channels and not by polymer degradation. The release rate was dependent on BSA loading and annealing. It may be concluded that PLA pellets can be fabricated suitably using BSA and annealing to design sustained-release preparations of water-soluble drugs.

  15. Physical-chemical aspects of a coaxial sustained release device based on Poly-Eva

    NARCIS (Netherlands)

    Laarhoven, Johannes Antonius Hendrikus van

    2005-01-01

    Sustained release of dugs offers several advantages like increased efficacy, safety, compliance and convenience. As a consequence sustained drug delivery is often preferred above daily administration of drugs. Furthermore, drug delivery systems can be designed to deliver one or more drugs at a speci

  16. Physical-chemical aspects of a coaxial sustained release device based on Poly-Eva

    NARCIS (Netherlands)

    Laarhoven, Johannes Antonius Hendrikus van

    2005-01-01

    Sustained release of dugs offers several advantages like increased efficacy, safety, compliance and convenience. As a consequence sustained drug delivery is often preferred above daily administration of drugs. Furthermore, drug delivery systems can be designed to deliver one or more drugs at a speci

  17. Development and characterisation of sustained release solid dispersion oral tablets containing the poorly water soluble drug disulfiram.

    Science.gov (United States)

    Shergill, Mandip; Patel, Mina; Khan, Siraj; Bashir, Ayesha; McConville, Christopher

    2016-01-30

    Administration of drugs via the oral route is the most common and preferred route due to its ease of administration, cost-effectiveness and flexibility in design. However, if the drug being administered has limited aqueous solubility it can result in poor bioavailability. Furthermore, the low pH of the stomach as well as enzymatic activity can result in drugs delivered via the oral route being rapidly metabolised and degraded. Here we demonstrate the development and characterisation of sustained release solid dispersion oral tablets, containing the poorly water-soluble drug disulfiram (DSF). The tablets, which are manufactured from two different polymers (Kolliphor(®) P 188 and P 237) specifically designed for the manufacture of solid dispersions and two different polymers (Kollidon(®) SR and HPMC) specifically designed to provide sustained release, can enhance the solubility of DSF, sustain its release, while protecting it from degradation in simulated gastric fluid (SGF). The paper demonstrates that when using the hot melt method at 80°C the DSF loading capacity of the Kolliphor(®) P 188 and P 237 polymers is approximately 43 and 46% respectively, with the DSF completely in an amorphous state. The addition of 80% Kollidon(®) SR to the formulation completely protected the DSF in SGF for up to 70 min with 16% degradation after 120 min, while 75% degradation occurred after 120 min with the addition of 80% HPMC. The release rate of DSF can be manipulated by both the loading and type of sustained release polymer used, with HPMC providing for a much faster release rate compared to Kollidon(®) SR.

  18. Losartan potassium loaded sustained release matrix tablets: Influence of various hydrophilic and hydrophobic polymers on drug release behaviour

    Directory of Open Access Journals (Sweden)

    D D Vohra

    2012-01-01

    Full Text Available Losartan potassium is an angiotensin II receptor antagonist readily absorbed from the GIT, following oral administration. It has low bioavailability as it undergoes extensive first pass metabolism and low elimination half-life. The present study was aimed at studying sustained release behaviour of the drug using hydrophilic and hydrophobic polymers and to optimise using a 32 full factorial design. Eudragit and HPMC were used to evaluate the effect of hydrophilic and hydrophobic polymers on the release pattern of the drug. A full factorial was implemented at 20, 30 and 40% concentration of hydrophilic polymer and 2.5, 5 and 7.5% of hydrophobic polymer correlating with the release behaviour. Process variables were investigated and the results showed excellent adaptability in releasing drug over prolonged periods. Based on the results, it was found suitable to formulate a dosage form using optimum concentration of hydrophobic polymer along with hydrophilic polymer to vary the release behaviour for over 12 hours.

  19. 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...... 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...... on the drug release from the two products. The 90% confidence intervals of the AUC(0-36) and C(max) ratios for the test and reference products were within the acceptable bioequivalence intervals of log0.8-log1.25. Conclusions: A HPMC-based SR tablet for tolterodine tartrate with a low release variation...

  20. 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

    . 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...

  1. Sustained release tablet of theophylline by hot melt wax coating technology

    OpenAIRE

    Padsalgi Amol; Bidkar Sanjay; Jadhav Vijay; Sheladiya Deepak

    2008-01-01

    Coating is one of the effective method used for sustaining the release of dosage form. There are various hydrophilic and hydrophilic polymers which are use to sustain the drug release. Waxes are one of the material which can be use to coat the drug in order to control the release. Coating with waxes can be achieved by dissolving it in suitable solvent or by hot melt wax coating. Hot melt coating technique defined as the application of fine layer of coating material in molten state over the su...

  2. Rechargeable calcium phosphate orthodontic cement with sustained ion release and re-release

    Science.gov (United States)

    Zhang, Ling; Weir, Michael D.; Chow, Laurence C.; Reynolds, Mark A.; Xu, Hockin H. K.

    2016-11-01

    White spot lesions (WSL) due to enamel demineralization are major complications for orthodontic treatments. Calcium phosphate (CaP) dental resins with Ca and P ion releases are promising for remineralization. However, previous Ca and P releases lasted for only weeks. Experimental orthodontic cements were developed using pyromellitic glycerol dimethacrylate (PMGDM) and ethoxylated bisphenol A dimethacrylate (EBPADMA) at mass ratio of 1:1 (PE); and PE plus 10% of 2-hydroxyethyl methacrylate (HEMA) and 5% of bisphenol A glycidyl dimethacrylate (BisGMA) (PEHB). Particles of amorphous calcium phosphate (ACP) were incorporated into PE and PEHB at 40% filler level. Specimens were tested for bracket-enamel shear bond strength, water sorption, CaP release, and ion recharge and re-release. PEHB+40ACP had higher bracket-enamel bond strength and ion release and rechargeability than PE+40ACP. ACP incorporation into the novel orthodontic cement did not adversely affect the bracket-enamel bond strength. Ion release and re-release from the novel ACP orthodontic cement indicated favorable release and re-release patterns. The recharged orthodontic cement could release CaP ions continuously for four weeks without further recharge. Novel rechargeable orthodontic cement containing ACP was developed with a high bracket-enamel bond strength and the ability to be repeatedly recharged to maintain long-term high levels of CaP ion releases.

  3. Demonstrating Encapsulation and Release: A New Take on Alginate Complexation and the Nylon Rope Trick

    Science.gov (United States)

    Friedli, Andrienne C.; Schlager, Inge R.; Wright, Stephen W.

    2005-01-01

    Three variations on a classroom demonstration of the encapsulation of droplets and evidence for release of the interior solution are described. The first two demonstrations mimic biocompatible applications of encapsulation. Reversible formation of capsules from aqueous solutions of sodium alginate, a negatively charged polysaccharide derived from…

  4. EFFECT OF NATURAL AND SYNTHETIC POLYMER ON RELEASE OF KETOTIFEN FUMARATE MATRIX TABLETS: A SUSTAINED RELEASE DOSAGE FORM

    Directory of Open Access Journals (Sweden)

    Md. M. Rahman*, A. B. Ripon Khalipha , Md. A. K. Azad , MD. Z. Faruki , A. K. Chaurasiya and H. Hossain

    2013-04-01

    Full Text Available ABSTRACT: With the blend of Methocel K15, a synthetic polymer and xanthan gum, a natural polymer (3:1 was used in the formulation of matrix tablets to find out the effect of natural polymer in the sustained release dosage form. Direct compression process was applied for the preparation of Ketotifen fumarate tablets. The dissolution profiles were carried out by USP apparatus 2 (paddle at 50 rpm in 500 ml 0.1 N HCl and distilled water. For interpreting the results a one way analysis of variance (ANOVA was exploited. Statistically significant differences were found among the drug release profile from different matrices. At a higher polymeric content (60% of the total tablet weight, drug release from the combination of Methocel K15M and xanthan gum (3:1 was slower. On the contrary, at a lower polymeric level (30% of the total tablet weight; the rate of drug release was prominent. The best-fit release kinetics was accomplished with the Higuchi model followed by the zero-order plot, Korsmeyer and Hixson Crowell equations. One formulation showed drug release is more controlled. The data obtained proved that the formulations are useful for a sustained release of ketotifen fumarate. From these formulations corresponded more controlled of the drug release by the higher polymeric level of methocel K15M & xanthan gum and vice versa. The extended release of the model drug found from the higher proportion of methocel K15M and xanthan gum. As a result, the frequency of administration of such type of drug reduced.

  5. 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.

  6. Adsorption of inorganic and organic ions to polycarbophil as a means of sustained-release dosage formulation.

    Science.gov (United States)

    See, N A; Russell, J; Connors, K A; Bass, P

    1987-06-01

    The adsorption and desorption of drugs and inorganic ions to and from polycarbophil (PC), a polymer, were investigated to determine if PC would be a suitable carrier for sustained-release dosage formulations. Both in vitro and in vivo experiments with a polycarbophil-atropine sulfate complex demonstrated the gradual-release properties of this system. Adsorbed Cr3+ ions, like atropine, are released slowly. In contrast, 51CrO4(2-) ions are predominantly bound in an irreversible manner. A third group of drugs minimally adsorbed to PC under the conditions studied. We conclude that PC under both in vitro and in vivo conditions is able to bind certain ions and drugs and then release them over a period of time in a predictable and repeatable manner.

  7. Novel Gelatin-Adriamycin Sustained Drug Release System for Intravesical Therapy of Bladder Cancer

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    To reduce recurrence in the patients with bladder cancer after tumor removal through open surgery or transurethral resection, a form of gelatin-adriamycin sustained drug release system was developed and its release kinetics both in vitro and in vivo, its efficacy in inhibiting BIU-87 bladder tumor cell growth in vitro and its safety in vivo were studied. The results showed that this system controlled adriamycin release over a period of 21 days in vitro and significantly inhibited BIU-87 cell growth. When this system was injected into rabbit bladder, it sustained adriamycin release for 12 days and the released drug could diffuse 1 cm around the injection point. No major complications were observed except minor acute nonspecific cystitis that could be tolerated well by the animals. This study suggests the possibility of applying this system locally in treating bladder cancer.

  8. 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

  9. Sustained release coating of tablets with Eudragit(®) RS/RL using a novel electrostatic dry powder coating process.

    Science.gov (United States)

    Qiao, Mingxi; Luo, Yanfeng; Zhang, Liqiang; Ma, Yingliang; Stephenson, Tyler Shawn; Zhu, Jesse

    2010-10-31

    The objectives of this study were to develop an electrostatic dry powder coating process for sustained coating tablets with Eudragit(®) RS/RL and to investigate the effects of various factors and operating conditions on the coating process and drug release profile. A liquid plasticizer (triethyl citrate) was sprayed onto the surface of the tablets followed by spraying coating powder by an electrostatic spray gun. The powder coated tablets were cured at elevated temperature for a film formation. Liquid plasticizer played important roles in lowering down the glass transition temperature (T(g)) of the coating polymer and increasing the surface electrical conduction of tablet cores. Electrostatic assisted coating deposition was confirmed by the fact that higher coating level was obtained with electrical charging than the ones without it. The micrographs of scanning electron microscopy (SEM) of coated tablets showed that the film formation mainly occurred during the curing step. Higher curing temperature and longer curing time help enhance the film formation. The in vitro drug release profiles indicated that curing time, temperature, coating level and ratio of Eudragit(®) RS/RL were the main factors affecting the sustained release profile. The electrostatic dry powder coating process has been demonstrated to be an alternative for tablet sustained release coating with Eudragit(®) RS and RL.

  10. 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.

  11. Formulation and Evaluation of sustained release matrix tablets of Glipizide

    Directory of Open Access Journals (Sweden)

    Shallu Sandhan*

    2013-12-01

    Full Text Available The aim of present investigation was to enhance the solubility of glipizide (BCS Class II. Glipizide is an oral antidiabetic agent with relatively short elimination half life. Inclusion complex of Glipizide with β-cyclodextrin was prepared by kneading method and evaluated for its in-vitro release. Phase solubility studies were performed according to method reported by Higuchi and Connors which was classified as AL type characterized by apparent 1:1 stability constant. The Glipizide & Beta Cyclodextrin found to be compatible which was observed from FTIR spectra of Glipizide β- CD Complex. The dissolution study of Glipizide β- CD complex shows significant increase in the drug release than pure drug. Matrix Glipizide β- CD complex tablet complex equivalent to 10 mg Glipizide were prepared by using Hydroxy propyl methyl cellulose (HPMC, Carboxy methyl cellulose sodium (NaCMC and Microcrytalline cellulose (MCC. The tablets were evaluated for various tests like hardness, friability, disintegration and in-vitro dissolution studies.

  12. Nanosized sustained-release pyridostigmine bromide microcapsules: process optimization and evaluation of characteristics

    Directory of Open Access Journals (Sweden)

    Tan Q

    2013-02-01

    Full Text Available Qunyou Tan,1,* Rong Jiang,3,* Meiling Xu,2,4,* Guodong Liu,5,* Songlin Li,1 Jingqing Zhang21Department of Thoracic Surgery, Institute of Surgery Research, Daping Hospital, Third Military Medical University, 2Medicine Engineering Research Center, Chongqing Medical University, 3Stem Cells and Tissue Engineering Research, Chongqing Medical University, 4Department of Pharmacy, Chongqing Emergency Medical Center, 5Eighth Department, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, People’s Republic of China*These authors contributed equally to this workBackground: Pyridostigmine bromide (3-[[(dimethylamino-carbonyl]oxy]-1-methylpyridinium bromide, a reversible inhibitor of cholinesterase, is given orally in tablet form, and a treatment schedule of multiple daily doses is recommended for adult patients. Nanotechnology was used in this study to develop an alternative sustained-release delivery system for pyridostigmine, a synthetic drug with high solubility and poor oral bioavailability, hence a Class III drug according to the Biopharmaceutics Classification System. Novel nanosized pyridostigmine-poly(lactic acid microcapsules (PPNMCs were expected to have a longer duration of action than free pyridostigmine and previously reported sustained-release formulations of pyridostigmine.Methods: The PPNMCs were prepared using a double emulsion-solvent evaporation method to achieve sustained-release characteristics for pyridostigmine. The preparation process for the PPNMCs was optimized by single-factor experiments. The size distribution, zeta potential, and sustained-release behavior were evaluated in different types of release medium.Results: The optimal volume ratio of inner phase to external phase, poly(lactic acid concentration, polyvinyl alcohol concentration, and amount of pyridostigmine were 1:10, 6%, 3% and 40 mg, respectively. The negatively charged PPNMCs had an average particle size of 937.9 nm

  13. 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

  14. Preparation and pharmacokinetics study on gastro-floating sustained-release tablets of troxipide.

    Science.gov (United States)

    Gao, Yunyun; Gao, Yang; Yin, Fei; Wang, Mi; Wang, Zhenhong; Ye, Tiantian; Yang, Yonggang; Pan, W S; Yang, Xinggang

    2015-01-01

    The purpose of this research aimed at preparing gastro-floating sustained-release tablets of troxipide and a further study on in vitro release and in vivo bioavailability. Under the circumstances of direct powder compression, the floating tablets were successfully prepared with HPMC as main matrix material, Carbopol as assistant matrix material, octadecanol as floating agent and sodium bicarbonate as foaming agent to float by gas-forming. The floating time and accumulative release amount as evaluation indexes were utilized to perform pre-experiment screening and single-factor test, respectively, while central composite design response surface method was applied for formulation optimization, followed by in vivo pharmacokinetic study in beagles after oral administration for floating tablets and commercial tablets used as the control. The results indicated that the floating sustained-release tablets held a better capability for floating and drug release and more satisfactory pharmacokinetic parameters, such as a lower Cmax, a prolonged Tmax, but an equivalent bioavailability calculated by AUC0-24 compared to commercial tablets. So a conclusion was finally drawn that the floating sustained-release tablets possessing a good release property could be suitable for demands of design.

  15. Eudragit RS PO nanoparticles for sustained release of pyridostigmine bromide

    Energy Technology Data Exchange (ETDEWEB)

    Hoobakht, Fatemeh; Ganji, Fariba, E-mail: fganji@modares.ac.ir; Vasheghani-Farahani, Ebrahim [Tarbiat Modares University, Biomedical Engineering Group, Chemical Engineering Department (Iran, Islamic Republic of); Mousavi, Seyyed Mohammad [Tarbiat Modares University, Biotechnology Group, Chemical Engineering Department (Iran, Islamic Republic of)

    2013-09-15

    Pyridostigmine bromide (PB) is an inhibitor of cholinesterase, which is used in the treatment of myasthenia gravis and administered for protection against exposure to toxic nerve agents. Tests were done to investigate prolonging the half-life of PB and improving its release behavior. PB was loaded in nanoparticles (NPs) of Eudragit RS PO (Eu-RS) prepared using the technique of quasi emulsion solvent diffusion. Variables of output power of the sonicator, bath temperature and mixing time, were chosen as the optimization factors to obtain the minimum sized NPs. In addition, emulsions were tested at different ratios of drug-to-polymer by dynamic light scattering to determine size and zeta potential of NPs. UV-spectroscopy was used to determine PB content of the NPs. Drug-loaded NPs were characterized by scanning electron microscopy, X-ray diffraction, and Fourier transform infrared spectra. Results determined that mixing time had a significant impact on the size of Eu-RS NPs, but power output of sonicator and bath temperature had no significant effect. The particle size obtained at the optimum condition (power output of 70 W, bath temperature of 33 Degree-Sign C, and mixing time of 7 min) was less than 200 nm (optimum sizes were 138.9 and 179.5 nm for Eu-RS and PB-loaded Eu-RS NPs, respectively). The optimum PB-loaded Eu-RS NPs at the PB to Eu-RS weight ratio of 1-4 and 20 % of loaded PB released from the nanocarriers within 100 h.

  16. A Practical Approach for Demonstrating Environmental Sustainability and Stewardship through a Net Ecosystem Service Analysis

    Directory of Open Access Journals (Sweden)

    Mark Rockel

    2013-05-01

    Full Text Available The increasing pressure on the earth’s resources due to population growth requires that development and resource use be managed to maintain a sustainable environment so as to preserve or enhance human well-being. A practical approach for demonstrating the environmental sustainability of an action (e.g., green business practice through ecosystem service analysis is presented. The overarching premise of the approach is that human well-being is directly related to changes in ecosystems and associated services. The approach evaluates the net change in ecosystem services, and hence human well-being, and is termed a net ecosystem service analysis (NESA. Using this approach, if a net positive change in ecosystem services relative to the baseline condition occurs for an action, that action would be considered potentially sustainable. In addition, if an action creates net ecosystem service value above the baseline condition, it would be considered to embody environmental stewardship. Established ecological and human use quantification methods are incorporated into the analysis. In addition, to demonstrate potential sustainability, the approach must also consider the need to satisfy intergenerational equity objectives. The use of a practical approach from which private business and government representatives can make decisions regarding environmental sustainability and stewardship will provide for improved decision-making based on quantifiable metrics.

  17. 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.

  18. Quaternary polymethacrylate-sodium alginate films: effect of alginate block structures and use for sustained release tablets.

    Science.gov (United States)

    Pongjanyakul, Thaned; Khuathan, Natnicha

    2016-01-01

    The objectives in this study were to characterize quaternary polymethacrylate-sodium alginate (QPM-SA) films prepared using high G block or high M block SA (GSA or MSA, respectively), and to investigate the effects of QPM-SA ratios, film-coating levels and SA block structures on propranolol HCl (PPN) released from coated tablets. The results demonstrated that GSA and MSA shared a similar interaction mechanism with QPM. The QPM-GSA films had higher puncture strength than the QPM-MSA films in dry and wet states, whereas the % elongations were not different. The drug permeability of the QPM-GSA films was lower than that of the QPM-MSA films in both acidic and neutral media, but higher water uptake of the QPM-GSA films was found at neutral pH. Moreover, the QPM-MSA-coated tablets had a greater PPN release rate than the QPM-GSA-coated tablets, and drug release was dependent on the film-coating levels. In addition, the QPM-SA films at a ratio of 4:0.5 produced a stronger film and could sustain PPN release. These results indicate that the QPM-GSA films had greater film strength and lower drug permeability than the QPM-MSA films. Additionally, the QPM-SA films have a strong potential for use in sustained-release tablets.

  19. Preparation and Characterization in vitro of Sustained-release Captopril/Chitosan-gelatin Net-polymer Microspheres(Cap/CGNPMs)

    Institute of Scientific and Technical Information of China (English)

    SONG Yimin; CHEN Xiguang; TANG Xuexi; LIU Chengshen; MENG Xianghong; YU Luojun

    2006-01-01

    The captopril/Chitosan-gelatin net-polymer microspheres (Cap/CGNPMs) were prepared using Chitosan(CS) and gelatin(Gel) by the methods of emulsification. A cross linked reagent alone or in combination with microcrystalline cellulose(MCC) was added in the process of preparation of microspheres to eliminate dose dumping and burst phenomenon of microspheres for the improvement of the therapeutic efficiency and the decrease of the side effects of captopril(Cap). The results indicate that Cap/CGNPMs have a spherical shape , smooth surface morphology and integral inside structure and no adhesive phenomena and good mobility,and the size distribution is mainly from 220 to 280 μm. Researches on the Cap release test in vitro demonstrate that Cap/CGNPMs are of the role of retarding release of Cap compared with Cap ordinary tablets (COT), embedding ratio (ER) ,drug loading (DL), and swelling ratio (SR), and release behaviors of CGNPMS are influenced by process conditions of preparation such as experimental material ratio (EMR) , composition of cross linking reagents. Among these factors , the EMR(1/4),CLR (FOR+TPP) and 0.75% microcrystalline cellulose (MCC) added to the microspheres are the optimal scheme to the preparation of Cap/CGNPMs. The Cap/CGNPMs have a good characteristic of sustained release of drug, and the process of emulsification and cross-linking process is simple and stable. The CGNPMs is probable to be one of an ideal sustained release system for water-soluble drugs.

  20. A hybrid thermo-sensitive chitosan gel for sustained release of Meloxicam.

    Science.gov (United States)

    Wang, Ye; Chen, Minyan; Li, Xiang; Huang, Yongzhuo; Liang, Wenquan

    2008-01-01

    The purpose of this work was to develop a multi-phase gel system for sustained release drug delivery. A thermo-sensitive hydrogel composed of chitosan and glycerol was prepared, and then an o/w emulsion was introduced to the thermo-sensitive gel in order to modulate the gelation behavior. Meloxicam was chosen as a model drug in this study and its release profile was investigated. This study revealed that the factors such as pH, chitosan molecular mass and glycerol concentration could significantly influence the gel formation. Chitosan with a molecular mass of 950 kDa and glycerol proportion ranging from 30 to 60% can form a pH-dependent thermo-sensitive gel system. Both the chitosan-glycerol gel and chitosan-glycerol-emulsion gel systems were applied in delivering drugs. The drug release from the two gels was both in Higuchi mode. Higuchi moduli were 3.04 x 10(-3) mg x h((1/2)) in the chitosan-glycerol-emulsion gel and 1.28 mg x h((1/2)) in the chitosan- glycerol gel. The former was significantly slower in sustained release. The in vivo investigation on the chitosan-glycerol gel indicated that the gel may be useful in sustained drug release in situ. Thermosensitive hydrogels composed of chitosan and glycerol were well formed and could act as a sustained release drug carrier in the work, it showed that this hybrid thermo-sensitive hydrogel system may be a promising sustained release drug carrier.

  1. Formulation and in vitro evaluation of sustained release dosage form with taste masking of metformin hydrochloride

    Directory of Open Access Journals (Sweden)

    Bhoyar P

    2010-01-01

    Full Text Available An attempt was made to sustain the release of metformin HCl as well as to mask the bitter taste by complexation technique using strong cation-exchange resins, indion 244 and indion 264. The drug loading onto ion-exchange resin was optimized for mixing time, activation, effect of pH, mode of mixing, ratio of drug:resin and temperature. The resinate was evaluated for micromeritic properties, taste masking and characterized using XRPD and IR. Using resinate sustained release tablets were formulated using hydoxypropylmethylcellulose K100M.The tablets were evaluated for hardness, thickness, friability, drug content, weight variation and in vitro drug release. Tablets thus formulated (Batch B-6 provided sustained release of drug over a period of 10 h with first order kinetics. The release of metformin HCl from resinate controls the diffusion of drug molecules through the polymeric material into aqueous medium. Results showed that metformin HCl was successfully taste masked and formulated into a sustained dosage form as an alternative to the conventional tablet.

  2. Preparation of sustained-release composite coating formed by dexamethasone and oxidated sodium alginate.

    Science.gov (United States)

    Gao, Wenqing; Li, Tong; Yu, Meili; Hu, Xiaomin; Duan, Dawei; Lin, Tingting

    2014-01-01

    Inflammatory reaction and thrombosis are the unsolved main problems of non-coated biomaterials applied in cardiac surgery. In the present study, a series of sustained composite coating was prepared and characterized, such as in the chemical modification of polyvinyl chloride (PVC) for applications in cardiac surgery and the assessment of the biological property of modified PVC. The composite coatings were mainly formed by dexamethasone (DXM) and oxidated sodium alginate (OSA) through ionic and covalent bond methods. The biocompatibility and hemocompatibility of the coating surface were evaluated. Scanning electron microscopy analysis of the surface morphologies of the thrombus and platelets revealed that DXM-OSA coating improved the antithrombogenicity and biocompatibility of PVC circuits, which were essential for cardiac pulmonary bypass surgery. Evaluation of in vitro release revealed that the DXM on group PPC was gradually released in 8 h. Thus, DXM that covalently combined on the PVC surface showed sustained release. By contrast, DXM on groups PPI and PPD was quickly or shortly released, suggesting that groups PPI and PPD did not have sustained-release property. Overall, results indicated that the DXM-OSA composite coating may be a promising coating for the sustained delivery of DXM.

  3. Sustained-release pellets of nifedipine using microcrystals combined with MCC-based matrix.

    Science.gov (United States)

    Ma, Jinlong; Wang, Juan; Cheng, Zhibo; Yin, Tian; Teng, Huan; Xu, Hui; Tang, Xing; Cai, Cuifang

    2015-02-01

    The purpose of this study was to prepare sustained-release pellets of nifedipine (NSPs) based on MCC matrix. Wet-milling and extrusion-spheronization techniques were employed to prepare the microcrystals and pellets, respectively. The drug release mechanism and the influencing factors were investigated. After milled with HPMC (E5), the mean particle size of nifedipine in co-grinding mixture (CGM) was 5 μm, which is 15-fold smaller than that of raw material. DSC, X-ray powder diffraction and microscopic observation confirmed the microcrystals of drug were maintained in the CGM. With increased milling time and the content of HPMC, the dissolution rate was greatly enhanced compared with the raw material. The NSPs prepared by MCC and the CGM, which was obtained by cogrinding nifedipine with 5% HPMC solution for 210 min, exhibited sustained release pattern within 8 h. Nifedipine release from MCC-based NSPs followed the Korsmeyer model and closely related to the microstructure of pellet. High stability of NSPs was confirmed after 6 months of accelerated stability test. Using commercially available sustained product as reference, bioequivalence study in beagle dogs was executed and two formulations were bioequivalent. This sustained release pellet formulation of nifedipine was advantageous with convenient and easy scaled-up preparation process.

  4. Nanostructured liquid crystalline particles provide long duration sustained-release effect for a poorly water soluble drug after oral administration.

    Science.gov (United States)

    Nguyen, Tri-Hung; Hanley, Tracey; Porter, Christopher J H; Boyd, Ben J

    2011-07-30

    This study is the first to demonstrate the ability of nanostructured liquid crystal particles to sustain the absorption of a poorly water soluble drug after oral administration. Cubic (V(2)) liquid crystalline nanostructured particles (cubosomes) formed from phytantriol (PHY) were shown to sustain the absorption of cinnarizine (CZ) beyond 48h after oral administration to rats. Plasma concentrations were sustained within the range of 21.5±1.5ng/mL from 12 to 48h. In stark contrast, cubosomes prepared using glyceryl monooleate (GMO) did not sustain the absorption of CZ and drug concentrations fell below quantifiable levels after 24h. Sustained absorption of CZ from PHY cubosomes lead to a significant enhancement (pnanostructured particles in simulated gastric and intestinal fluids using small angle x-ray scattering (SAXS) revealed that the V(2)Pn3m nanostructure of PHY cubosomes was maintained for extended periods of time, in contrast to GMO cubosomes where the V(2)Im3m nanostructure was lost within 18h after exposure, suggesting that degradation of the LC nanostructure may limit sustained drug release. In addition, PHY cubosomes were shown to be extensively retained in the stomach (>24h) leading to the conclusion that in the case of non-digestible PHY cubosomes, the stomach may act as a non-sink reservoir that facilitates the slow release of poorly water soluble drugs, highlighting the potential use of non-digestible LC nanostructured particles as novel sustained oral drug delivery systems. Copyright © 2011 Elsevier B.V. All rights reserved.

  5. Formulation and evaluation of floating tablets of niacin for sustained release

    Directory of Open Access Journals (Sweden)

    Haripriya Puthoori

    2012-01-01

    Full Text Available Niacin or nicotinic acid (NA is used in the treatment of hyperlipidemia. NA immediate release formulation shows undesirable effects like flushing of the face and neck parts. In the present study, NA floating sustained release dosage form was developed to prolong the drug release, to retain the drug delivery system above the site of absorption for the desired period of time, and to reduce the drug release rate compared to conventional formulations in order to minimize the side effects. The preformulation parameters such as flow properties and drug-excipient compatibility studies were performed. The drug excipient compatibility studies were performed using the FTIR study and the results showed that all the polymers used in the study are compatible with the pure drug. The floating sustained release tablets of niacin were prepared by the wet granulation method and the granules were evaluated for various micromeritic properties like bulk density, tapped density, Carr′s Index, Hausner′s ratio, and angle of repose. The tablets were evaluated for post-compressional parameters like average weight, thickness, hardness, friability, swelling index, floating lag time and total floating time, and in vitro drug release studies. All the formulations showed total floating time >20 hr. The concentration of the effervescent agent and the concentration and type of polymer showed an effect on the floating behavior and drug release. The formulation containing 13% sodium bicarbonate, HPMC (33% and Eudragit RS PO (4% showed required drug release up to 20 hr.

  6. Formulation and optimization of sustained release tablets of venlafaxine resinates using response surface methodology

    Directory of Open Access Journals (Sweden)

    Madgulkar Ashwini

    2009-01-01

    Full Text Available The aim of the current study was to design sustained release matrix tablets of venlafaxine hydrochloride using ion exchange resin with the incorporation of hydrophilic and hydrophobic polymer combinations. Venlafaxine HCl was loaded onto Indion 244 by batch method and then resinate were wet granulated with ethyl cellulose and blended with hydroxypropylmethylcellulose and compressed. A central composite design for 2 factors at 3 levels each was employed to systematically optimize drug release profile at 2 h and at 18 h. Hydroxypropylmethylcellulose and ethylcellulose were taken as the independent variables. Response surface plots and contour plots were drawn, and optimum formulations were selected by feasibility and grid searches. Resinate shows inadequate sustained release profile. Compressed matrices exhibited the anomalous release mechanism, as the value of release rate exponent (n varied between 08109 and 08719, resulting in regulated and complete release until 20 h. Validation of optimization study, performed using five confirmatory runs, indicated very high degree of prognostic ability of response surface methodology, with mean percentage error as 1.152±1.88%. Regulated drug release study indicates that the hydrophilic and hydrophobic matrix tablets of venlafaxine resinate prepared using hydroxypropylmethylcellulose and ethylcellulose, can successfully be employed as a once-a-day oral controlled release drug delivery system.

  7. Novel sustained-release of Stryphnodendron obovatum leaves extract using natural rubber latex as carrier

    Directory of Open Access Journals (Sweden)

    Felipe Azevedo Borges

    2016-07-01

    Full Text Available Natural rubber latex biomembranes (NRL, obtained from rubber tree Hevea brasiliensis (Willd. ex A. Juss. Mull. Arg., have been used as sustained drug release of drugs and plant extracts with medicinal properties. The Stryphnodendron obovatum Bench (Fabaceae, popularly known as “barbatimão” has anti-inflammatory and healing properties already described in literature. Thus, the aim of this work were to study the release behavior of the hydroethanolic extract from the leaves of S. obovatum loaded in the NRL by ultraviolet–visible spectroscopy (UV-VIS. The release followed a bi- exponential pattern and the mechanism of release was Super Case II (n > 1. FTIR analyses did not show reaction between NRL and extract, only intermolecular interaction. From SEM was possible to observe the extract at the surface, responsible for the initial fast release, which the concentrations at 5.0 mg/mL released 2.4% and at 0.1 mg/mL released 96.8%; both reached the plateau in 7 days.Keywords: Stryphnodendron obovatum. Hevea brasiliensis. Sustained release. Barbatimão. Tannin. Natural rubber latex.  

  8. Sustained Release Floating Microspheres Of Acyclovir: Formulation, Optimization, Characterization And In Vitro Evaluation

    Directory of Open Access Journals (Sweden)

    Parmar Kunal Vinodbhai

    2011-03-01

    Full Text Available The aim of the present work was to prepare floating microspheres of acyclovir to prolong residence time in stomach and to sustain the release of acyclovir. Acyclovir loaded floating microspheres were prepared by double emulsion solvent evaporation method. The 32 full factorial design was applied to optimize the formulation. The resultant microspheres were evaluated for average particle size, percentage encapsulation efficiency, in vitro drug release and model fitting kinetics. Scanning electron microscopy, Fourier transform infrared (FTIR spectroscopy and differential scanning calorimetry were used to investigate the physical state of the drug in the microspheres. The particle size of microspheres was in the range of 275-340 µm. Percentage encapsulation efficiency was between 59%-77% w/w. Microspheres remained buoyant for more than about 12 h. The results of FT-IR spectroscopy and differential scanning calorimetry indicated the stable character of acyclovir in microspheres and also revealed absence of drugpolymer interaction. The in vitro drug release study showed that acyclovir release from the microspheres was slow and sustained for more than about 10 h. Drug release followed Korsemeyer-peppas model. The results of factorial batches revealed that the concentration of ethyl cellulose and stirring speed significantly affected drug encapsulation efficiency and particle size of the microspheres. Thus we can conclude that floating microspheres can successfully be developed to sustain the drug release.

  9. 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.

  10. Preliminary exploration of the development of a collagenous artificial dura mater for sustained antibiotic release

    Institute of Scientific and Technical Information of China (English)

    WANG Hao; DONG Hui; KANG Cheng-gui; LIN Cheng; YE Xun; ZHAO Yuan-li

    2013-01-01

    Background Intracranial infection is one of the most common complications of open craniocerebral injury and of conventional craniotomy in neurosurgery.The presence of blood-brain barrier leads to lower drug concentrations in the cerebrospinal fluid than in the venous blood.Increasing the intravenous dosage or frequency carries the risk of systemic adverse reactions or infections in other parts of the body.Developing an artificial dura mater (ADM) for sustained antibiotic release for use during neurosurgery can solve the problems perfectly.Methods Three types of drug-loaded ADMs made of collagen and containing cefuroxime sodium,ceftriaxone sodium,or norvancomycin were prepared.The antibacterial activity and sustained release characteristics of the ADMs were examined using bacteriostatic and release tests.Results Single-layered collagen based ADMs (40 mm×50 mm×5 mm) containing 18 mg cefuroxime sodium or ceftriaxone sodium were not suitable for continued development because of drug preservation and stability issues.Using smaller ADMs (20 mm×30 mm×7 mm),containing 4.86 mg of norvancomycin,with increased collagen density and a three-layered film with two outer drug-free films above and below the antibiotic layer resulted in sustained cumulative release of 2.91 mg (59.9%) of norvancomycin over 72 hours.The similar factor (f2) comparison method proved that products from a same batch were statistically significant similar (f2 >50).Conclusions Artificial ADMs made of collagen can be processed to provide a mature dural repair material for the sustained release of norvancomycin.This system may provide a basis for developing sustained release materials for other drugs.

  11. Sustained-release progesterone nanosuspension following intramuscular injection in ovariectomized rats

    Directory of Open Access Journals (Sweden)

    Heba F Salem

    2010-11-01

    Full Text Available Heba F SalemFaculty of Pharmacy, Beni-Suef University, Beni-Suef, EgyptAbstract: The production of an intramuscular (IM injection of natural progesterone would provide a safer solution than using semi synthetic progesterone. However, disadvantages such as low solubility and a short half life prevent the use of natural progesterone. In this study, we formulated a sustained release form of natural progesterone to be given as IM injection. A progesterone nanosuspension (PNS was first developed and then dispersed in a thermosensitive gel matrix. The selected nanoparticles showed an average particle size of 267 nm and a zeta potential approaching-41 mV. The in vitro release profile of PNS from the F127 plus methyl cellulose gel followed zero order kinetics and correlated linearly with the weight percentage of gel dissolved, demonstrating that the overall rate of release of PNS is controlled by dissolution of the pluronic F127/methyl cellulose (MC gel (r2 > 0.99. The pharmacokinetic parameters of the PNS (6 mg/mL in pluronic F127/MC gel were evaluated in comparison with the control progesterone suspension. After the administration of PNS in F127/MC gel into the rats, a maximum serum concentration of 22.1 ± 1.9 ng/mL was reached at a Tmax of 4.05 ± 0.1 h. The terminal half life was 12.7 ± 0.8 h. The area under the curve AUC0-∞ of the injected formula was 452.75 ± 42.8 ng•h/mL and the total mean residence time was 18.57 ± 1.44 h. The PNS in gel was significantly different from the control in rate and extent at P < 0.001. The natural progesterone which was nanosized and formulated in a thermosensitive gel significantly sustained the action of natural progesterone so that it could be injected every 36 h instead of every day. Moreover, this formula is expected to provide a much safer choice than the use of semi-synthetic progesterone.Keywords: progesterone, nanosuspension, thermosensitive gel, ovariectomized female rats

  12. Formulation and development of pH-independent/dependent sustained release matrix tablets of ondansetron HCl by a continuous twin-screw melt granulation process.

    Science.gov (United States)

    Patil, Hemlata; Tiwari, Roshan V; Upadhye, Sampada B; Vladyka, Ronald S; Repka, Michael A

    2015-12-30

    The objective of the present study was to develop pH-independent/dependent sustained release (SR) tablets of ondansetron HCl dihydrate (OND), a selective 5-HT3 receptor antagonist that is used for prevention of nausea and vomiting caused by chemotherapy, radiotherapy and postoperative treatment. The challenge with the OND API is its pH-dependent solubility and relatively short elimination half-life. Therefore, investigations were made to solve these problems in the current study. Formulations were prepared using stearic acid as a binding agent via a melt granulation process in a twin-screw extruder. The micro-environmental pH of the tablet was manipulated by the addition of fumaric acid to enhance the solubility and release of OND from the tablet. The in vitro release study demonstrated sustained release for 24h with 90% of drug release in formulations using stearic acid in combination with ethyl cellulose, whereas 100% drug release in 8h for stearic acid-hydroxypropylcellulose matrices. The formulation release kinetics was correlated to the Higuchi diffusion model and a non-Fickian drug release mechanism. The results of the present study demonstrated for the first time the pH dependent release from hydrophilic-lipid matrices as well as pH independent release from hydrophobic-lipid matrices for OND SR tablets manufactured by means of a continuous melt granulation technique utilizing a twin-screw extruder.

  13. 21 CFR 520.1921 - Prochlorperazine, isopropamide, with neomycin sustained-release capsules.

    Science.gov (United States)

    2010-04-01

    ... sustained-release capsules. 520.1921 Section 520.1921 Food and Drugs FOOD AND DRUG ADMINISTRATION... capsules. (a) Specifications. Each capsule contains either: (1) Capsule No. 1: 3.33 milligrams of... base (as the sulfate); or (2) Capsule No. 3: 10 milligrams of prochlorperazine (as the dimaleate), 5...

  14. 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.

  15. 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.

  16. Preparation of coated valproic acid and sodium valproate sustained-release matrix tablets

    Directory of Open Access Journals (Sweden)

    Phaechamud T

    2010-01-01

    Full Text Available 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; .

  17. Amphiphilic Beads as Depots for Sustained Drug Release Integrated into Fibrillar Scaffolds

    Science.gov (United States)

    Gaharwar, Akhilesh K.; Mihaila, Silvia M.; Kulkarni, Ashish A.; Patel, Alpesh; Di Luca, Andrea; Reis, Rui L.; Gomes, Manuela E.; van Blitterswijk, Clemens; Moroni, Lorenzo; Khademhosseini, Ali

    2014-01-01

    Native extracellular matrix (ECM) is a complex fibrous structure loaded with bioactive cues that affects the surrounding cells. A promising strategy to mimicking native tissue architecture for tissue engineering applications is to engineer fibrous scaffolds using electrospinning. By loading appropriate bioactive cues within these fibrous scaffolds, various cellular functions such as cell adhesion, proliferation and differentiation can be regulated. Here, we report on the encapsulation and sustained release of model hydrophobic drug (dexamethasone (Dex)) within beaded fibrillar scaffold of poly(ethylene oxide terephthalate)-poly(butylene terephthalate) (PEOT/PBT), a polyether-ester multiblock copolymer to direct differentiation of human mesenchymal stem cells (hMSCs). The amphiphilic beads act as depots for sustained drug release that is integrated into the fibrillar scaffolds. The entrapment of Dex within the beaded structure results in sustained release of drug over the period of 28 days. This is mainly attributed to the diffusion driven release of Dex from the amphiphilic electrospun scaffolds. In vitro results indicate that hMSCs cultured on Dex containing beaded fibrillar scaffolds exhibit an increase in osteogenic differentiation potential, as evidenced by increased alkaline phosphatase (ALP) activity, compared to the direct infusion of Dex in culture medium. The formation of mineralized matrix is also significantly enhanced due to the controlled Dex release from the fibrous scaffolds. This approach can be used to engineer scaffolds with appropriate chemical cues to direct tissue regeneration. PMID:24794894

  18. 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.

  19. Simvastatin-loaded PLGA nanoparticles for improved oral bioavailability and sustained release: Effect of formulation variables

    Directory of Open Access Journals (Sweden)

    Aman Soni

    2011-01-01

    Full Text Available The objective of this study was to prepare a nanoparticulate formulation of simvastatin (SV for improving oral bioavailability and sustaining the drug release while investigating the effect of various formulation parameters on characteristics of nanoparticles. Nanoparticles containing SV were prepared by a modified emulsification solvent evaporation technique using a biodegradable polymer, poly(d,l-lactide-coglycolide (PLGA as a sustained release carrier. The effect of various formulation parameters such as drug polymer ratios (SV:PLGA, 1:4 to 1:1, organic solvents (methanol/dichloromethane, and surfactants (PVA/polysorbate-80 in a fixed concentration (0.5%, w/v were studied for particle size, drug loading, and entrapment efficiency. Nanoparticles were characterized by differential scanning calorimetry (DSC and their shapes were observed by scanning electron microscopy (SEM. An aqueous solubility study indicated that the dissolution rates were remarkably increased for nanoparticles compared with the drug alone. The in vitro drug release study of the nanoparticles showed a biphasic release pattern: one initial burst release of 40.56% in the first 4 h which can be helpful to improve the penetration of drug followed by a second slow-release phase (extended release consistent with a Higuchi diffusion mechanism. The hypolipidemic activity of nanoparticles was determined in comparison with SV in male Wistar rats for changes in total cholesterol (CH and triglyceride (TG levels in blood. Nanoparticles showed a significantly better in vivo performance than SV in reducing total CH and TG levels which is primarily attributed to the improved solubility and dissolution of nanoparticles. Together, these results indicate that nanoparticulate formulations are ideal carriers for oral administration of SV having great potential to improve the oral bioavailability and sustain the drug release, thereby minimizing the dose-dependent adverse effects and maximizing

  20. Role of demonstration projects in innovation: transition to sustainable energy and transport

    DEFF Research Database (Denmark)

    Klitkou, Antje; Coenen, Lars; Andersen, Per Dannemand

    2013-01-01

    Transition towards more sustainability has been on the agenda of politicians, researchers, industry and concerned societal actors for a number of years. The oil crisis in the 1970s, environmental concerns related to decreasing biodiversity, depleted natural resources, cities polluted by emissions...... guidance for compiling a comprehensive database over all relevant demonstration projects and programmes in the three Scandinavian countries, a survey of the identified projects and programmes and interviews with involved stakeholders....

  1. Microstructured dextran hydrogels for burst-free sustained release of PEGylated protein drugs.

    Science.gov (United States)

    Bae, Ki Hyun; Lee, Fan; Xu, Keming; Keng, Choong Tat; Tan, Sue Yee; Tan, Yee Joo; Chen, Qingfeng; Kurisawa, Motoichi

    2015-09-01

    Hydrogels have gained significant attention as ideal delivery vehicles for protein drugs. However, the use of hydrogels for protein delivery has been restricted because their porous structures inevitably cause a premature leakage of encapsulated proteins. Here, we report a simple yet effective approach to regulate the protein release kinetics of hydrogels through the creation of microstructures, which serve as a reservoir, releasing their payloads in a controlled manner. Microstructured dextran hydrogels enable burst-free sustained release of PEGylated interferon over 3 months without compromising its bioactivity. These hydrogels substantially extend the circulation half-life of PEGylated interferon, allowing for less frequent dosing in a humanized mouse model of hepatitis C. The present approach opens up possibilities for the development of sustained protein delivery systems for a broad range of pharmaceutical and biomedical applications.

  2. Evaluation of gum sandarac as a novel release controlling coating polymer for formulation of sustained release pellets

    Directory of Open Access Journals (Sweden)

    Deepak S. Khobragade

    2016-04-01

    Full Text Available Polymeric coating techniques have been widely used in the pharmaceutical industries for diversified reasons. Various materials are being investigated as polymers as there is scarcity of good polymeric materials to be used in pharmaceutical products. The present study was aimed at evaluating novel natural material gum sandarac, a resin obtained by incision from the stem of Callitris quadrivalvis, Ventenat (N.O. Coniferae Pinaceae as a coating material for developing coated pellets for sustained release of drug and comparing it with  well known ethyl cellulose as hydrophobic polymeric material. Drug layered NPS, drug loaded pellets prepared with extrusion spheronization and NPS coated with drug polymer matrix were used as multi particulate formulation. The results indicate that Gum Sandarac is very efficient in retarding release of drugs from different pellet formulations yielding very superior quality pellet.

  3. Sustained antiemetic responses with APF530 (sustained-release granisetron) during multiple cycles of emetogenic chemotherapy.

    Science.gov (United States)

    Boccia, Ralph; Cooper, William; O'Boyle, Erin

    2015-02-01

    A phase 3 trial in patients with cancer who received chemotherapy has shown that subcutaneous (SC) APF530, a sustained-delivery formulation of granisetron, is noninferior to palonosetron in preventing acute (0-24 hours) and delayed (>24-120 hours) chemotherapy-induced nausea and vomiting (CINV). To investigate the sustainability of APF530 antiemetic responses during multiple chemotherapy cycles. 1,395 patients receiving moderately or highly emetogenic chemotherapy (MEC and HEC, respectively) were randomized either to APF530 250 or 500 mg SC (containing granisetron 5 or 10 mg, respectively) or palonosetron 0.25 mg intravenously before cycle 1 of chemotherapy. Patients who received palonosetron in cycle 1 were rerandomized in cycles 2-4 to APF530 250 or 500 mg; those who received APF530 in cycle 1 continued their APF530 dose. Between-group response rates were compared using the Fisher exact test. Complete response (CR; no emesis, no rescue medication) for APF530 500 mg with HEC increased from 81.3% to 87.8% over 4 cycles in the acute phase of CINV, and from 67.1% to 83.1% in the delayed phase. Rates were slightly lower with MEC. Within-cycle CR rates between APF530 doses showed no significant differences. With HEC, APF530 500 mg provided sustained CRs through 4 cycles of chemotherapy in 68.4% of patients in the acute phase and in 57.9% in the delayed phase; with MEC, corresponding CRs were 56.5% and 41.3%. Nausea prevention was nearly as effective as emesis prevention. Chemotherapy emetogenicity was classified according to Hesketh criteria during the time of this study. However, subsequent post hoc analyses indicate that reclassification according to newer ASCO emetogenicity guidelines did not alter the original study noninferiority conclusions. CR rates with APF530 during the acute and delayed phases of CINV in MEC and HEC were maintained over multiple cycles. ©2015 Frontline Medical Communications.

  4. Calcium binding-mediated sustained release of minocycline from hydrophilic multilayer coatings targeting infection and inflammation.

    Directory of Open Access Journals (Sweden)

    Zhiling Zhang

    Full Text Available Infection and inflammation are common complications that seriously affect the functionality and longevity of implanted medical implants. Systemic administration of antibiotics and anti-inflammatory drugs often cannot achieve sufficient local concentration to be effective, and elicits serious side effects. Local delivery of therapeutics from drug-eluting coatings presents a promising solution. However, hydrophobic and thick coatings are commonly used to ensure sufficient drug loading and sustained release, which may limit tissue integration and tissue device communications. A calcium-mediated drug delivery mechanism was developed and characterized in this study. This novel mechanism allows controlled, sustained release of minocycline, an effective antibiotic and anti-inflammatory drug, from nanoscale thin hydrophilic polyelectrolyte multilayers for over 35 days at physiologically relevant concentrations. pH-responsive minocycline release was observed as the chelation between minocycline and Ca(2+ is less stable at acidic pH, enabling 'smart' drug delivery in response to infection and/or inflammation-induced tissue acidosis. The release kinetics of minocycline can be controlled by varying initial loading, Ca(2+ concentration, and Ca(2+ incorporation into different layers, enabling facile development of implant coatings with versatile release kinetics. This drug delivery platform can potentially be used for releasing any drug that has high Ca(2+ binding affinity, enabling its use in a variety of biomedical applications.

  5. Formulation and evaluation of sustained release matrix tablet of rabeprazole using wet granulation technique

    Directory of Open Access Journals (Sweden)

    Ruqaiyah Khan

    2014-01-01

    Full Text Available Introduction: Rabeprazole, a member of substituted benzimidazoles, inhibits the final step in gastric acid secretions. This drug claims to cause fastest acid separation (due to higher pKa, and more rapidly converts to the active species to aid gastric mucin synthesis. The most significant pharmacological action of Rabeprazole is dose dependent suppression of gastric acid secretion; without anticholinergic or H2-blocking action. It completely abolishes the hydrochloric acid secretion as it is powerful inhibitor of gastric acid. Rabeprazole is acid labile and hence commonly formulated as an enteric coated tablet. The absorption of rabeprazole occurs rapidly as soon as tablet leaves the stomach. Aim: In the present study an attempt was made to formulate and evaluate Rabeprazole sustained release matrix tablet using wet granulation technique incorporating various polymers like HPMC-E15, Carbopol934, and sodium carboxymethyl cellulose (CMC. Materials and Methods: The Formulated tablets were evaluated for different physicochemical properties like rheological properties, weight variation, thickness, hardness, % friability, in vitro release studies and drug content. Results: Studies revealed that all the physicochemical parameters comply with the official standards. The in vitro release studies exhibits the release up to 90%, over a prolonged period of time which confirms the extended release profile of formulation, having better bioavailability as well as decreased dosing frequency with reduced doses. Conclusion: The sustained release matrix tablets of rabiprazole shown better bioavailability, efficacy and potency, when compared with official standards.

  6. Sustained Release of Vancomycin from Polyurethane Scaffolds Inhibits Infection of Bone Wounds in a Rat Femoral Segmental Defect Model

    Science.gov (United States)

    2010-04-09

    a one shot two component reaction between the triisocyanate and the hardener comprising polyester triol, water, TEGOAMIN33 tertiary amine catalyst ...Sustained release of vancomycin from polyurethane scaffolds inhibits infection of bone wounds in a rat femoral segmental defect model Bing Li a,b...2010 Keywords: Polyurethane Vancomycin Sustained release Infection control Rat femoral segmental defect Bone tissue engineering Infection is a common

  7. 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.

  8. 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.

  9. 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

  10. Sustained-release pregabalin with methylcobalamin in neuropathic pain: an Indian real-life experience

    Directory of Open Access Journals (Sweden)

    Dongre YU

    2013-05-01

    Full Text Available Yasmin U Dongre, Onkar C Swami Unichem Laboratories Ltd, Unichem Bhavan, Mumbai, India Introduction: Neuropathic pain is intense in nature and difficult to manage. Thus, the primary goal is maximum relief from pain. The aim of this study was to assess the efficacy and safety of a fixed-dose combination of sustained-release pregabalin and methylcobalamin in reducing neuropathic pain in Indian patients, in the real-life situation. Methods: This was a multicenter, prospective, open-labeled, single-arm, observational, 14-day study. Patients received fixed dose combination of 75 or 150 mg sustained-release pregabalin combined with 1500 mcg immediate release methylcobalamin, depending on the clinical requirement. Data was collected for pain reduction and other positive and negative symptoms associated with neuropathy, including hyperesthesia, paresthesia, numbness/tingling, burning sensation, muscle weakness, sleep disturbances, and impairment of movement. Pain intensity was measured on a ten-point visual analog scale (VAS (0 represented "no pain," and 10 represented "worst pain ever". The safety of the drug was also evaluated throughout the study duration. Data was analyzed using appropriate statistical methods. Results: The overall reduction in mean VAS score over 14 days was 72.3%. The reduction in mean VAS score was significant as early as the first week. Both positive and negative symptoms of peripheral neuropathy were significantly improved in >50% patients within the 2 weeks. Giddiness (4.7%, followed by sedation (3.6%, dizziness (2.9%, drowsiness (2.3%, and nausea (2.3% were the most commonly observed adverse effects. The overall efficacy and tolerability was rated as good to excellent by >95% of the investigators and patients. Conclusion: Fixed dose combination of sustained-release pregabalin and methylcobalamin significantly reduced neuropathic pain, with significant improvement in both the positive and negative symptoms associated with

  11. 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.

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

    DEFF Research Database (Denmark)

    Guo, Wenjia; Quan, Peng; Fang, Liang

    2015-01-01

    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...... 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...

  13. Preparation and in vitro evaluation of sustained release drug delivery system for verapamil HCL

    Directory of Open Access Journals (Sweden)

    Bhalekar M

    2007-01-01

    Full Text Available Verapamil HCl is a calcium channel blocker administered on thrice a day dosage regimen. In the present study resinates of verapamil HCl were formulated using Indion resins. Drug loading process was optimized with respect to drug:resin ratio, pH of loading solution, and particle size of resin. Resinates were characterized using XRPD. In vitro drug release rates from resinate was not adequately sustained. Hence resinates were incorporated in pellets using extrusion spheronization to achieve desired release pattern. Optimum drug loading was seen at pH of 3.5 in drug resin ratio of 1:1 and was seen to increase with temperature. XRPD studies revealed verapamil to be present in amorphous form in resinates. Drug release from resinates was complete in four hours. Resinates were pelletized using hydroxypropylmethylcellulose. Resinate of Indion 254 with 5% hydroxypropylmethylcellulose fulfilled USP criteria for extended release verapamil preparation.

  14. Review on Medusa:a polymer-based sustained release technology for protein and peptide drugs.

    Science.gov (United States)

    Chan, Y-P; Meyrueix, R; Kravtzoff, R; Nicolas, F; Lundstrom, K

    2007-07-01

    The polymer-based Medusa system (Flamel Technologies) has been designed for slow release of therapeutic proteins and peptides. The Medusa II consists of a poly L-glutamate backbone grafted with hydrophobic alpha-tocopherol molecules, creating a colloidal suspension of nanoparticles (10 - 50 nm) in water. The sustained drug release is based on reversible drug interactions with hydrophobic nanodomains within the nanoparticles. In vivo, it is suggested that the therapeutic protein is displaced by endogenous proteins present in physiological fluids, leading to a slow drug release. The peak concentration is dramatically decreased and the protein release substantially extended. The Medusa technology has been applied to subcutaneous injection for several therapeutic proteins, such as IL-2 and IFN-alpha(2b), in animal models (rats, dogs, monkeys) and clinical trials in renal cancer (IL-2) and hepatitis C (IFN-alpha(2b)) patients.

  15. Hydrolytic conversion of amorphous calcium phosphate into apatite accompanied by sustained calcium and orthophosphate ions release.

    Science.gov (United States)

    Niu, Xufeng; Chen, Siqian; Tian, Feng; Wang, Lizhen; Feng, Qingling; Fan, Yubo

    2017-01-01

    The aim of this study is to investigate the calcium and orthophosphate ions release during the transformation of amorphous calcium phosphate (ACP) to hydroxyapatite (HA) in aqueous solution. The ACP is prepared by a wet chemical method and further immersed in the distilled water for various time points till 14d. The release of calcium and orthophosphate ions is measured with calcium and phosphate colorimetric assay kits, respectively. The transition of ACP towards HA is detected by x-ray diffraction (XRD), transmission electron microscopy (TEM), and fourier transform infrared spectroscopy (FTIR). The results indicate that the morphological conversion of ACP to HA occurs within the first 9h, whereas the calcium and orthophosphate ions releases last for over 7d. Such sustained calcium and orthophosphate ions release is very useful for ACP as a candidate material for hard tissue regeneration.

  16. Setting radon-specific release criteria and demonstrating compliance for land affected by NORM

    Energy Technology Data Exchange (ETDEWEB)

    Garcia-Talavera, M. [Consejo de Seguridad Nuclear (CSN), Justo Dorado 11, E-28040 Madrid (Spain)], E-mail: mgtm@csn.es; Martinez, M.; Matarranz, J.L.M.; Ramos, L. [Consejo de Seguridad Nuclear (CSN), Justo Dorado 11, E-28040 Madrid (Spain)

    2008-11-15

    Residues from industrial activities involving naturally occurring radioactive materials (NORMs) may cause radiation exposures to members of the public, particularly when NORM-affected land is brought into residential use. To provide an adequate protection against radiation in such situations, the following limiting criteria are currently required in Spain for releasing NORM-affected land: (i) no more than a 300 {mu}Sv yr{sup -1} increase (excluding radon doses) over the natural background; (ii) {sup 222}Rn concentrations in hypothetical future dwellings lower than 200 Bq m{sup -3}; and (iii) reduction of all radiation exposures to as low as reasonable achievable. This paper addresses some of the problems encountered in translating the {sup 222}Rn criterion into site-specific release limits and in demonstrating compliance with them.

  17. Preparation of codeine-resinate and chlorpheniramine-resinate sustained-release suspension and its pharmacokinetic evaluation in beagle dogs.

    Science.gov (United States)

    Zeng, Huan-Xiang; Cheng, Gang; Pan, Wei-San; Zhong, Guo-Ping; Huang, Min

    2007-06-01

    the release rate of both drugs. But the release of codeine from its resinate beads was much more rapid than chlorpheniramine released from its resinate beads in the same ionic strength release medium. The drug release specification of the CCSS, where release mediums were 0.05 M KCl solution for codeine and 0.5 M KCl solution for chlorpheniramine, was established to be in conformance with in vivo performance. Relative bioavailability and pharmacokinetics evaluation of the CCSS, using commercial immediate-release tablets as the reference preparation, were performed following a randomized two-way crossover design in beagle dogs. The drug concentrations in plasma were measured by a validated LC-MS/MS method to determine the pharmacokinetic parameters of CCSS. This LC-MS/MS method demonstrated high accuracy and precision for bioanalysis, and was proved quick and reliable for the pharmacokinetic studies. The results showed that the CCSS had the longer value of Tmax and the lower value of Cmax, which meant an obviously sustained release effect, and its relative bioavailability of codeine and chlorpheniramine were (103.6 +/- 14.6)% and (98.1 +/- 10.3)%, respectively, compared with the reference preparation. These findings indicated that a novel liquid sustained release suspension made by using IERs as carriers and subsequent fluidized bed coating might provide a constant plasma level of the active pharmaceutical ingredient being highly beneficial for various therapeutic reasons.

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

    OpenAIRE

    Suhas, Khandave; Satish ,Sawant; Santosh ,Joshi; Bansal,Yatish Kumar; Sonal Sushil Kadam,

    2010-01-01

    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 tramado...

  19. 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.

  20. Pharmacokinetic evaluation of a new oral sustained release dosage form of tramadol

    Science.gov (United States)

    Malonne, H; Sonet, B; Streel, B; Lebrun, S; De Niet, S; Sereno, A; Vanderbist, F

    2004-01-01

    Aims To compare the pharmacokinetic profile of a new modified release formulation of tramadol (Tramadol LP 200 mg, SMB Technology, Marche-en-Famenne, Belgium) with that of an immediate release capsule (Topalgic® 50 mg, Grünenthal, Aachen, Germany) after single and multiple dosing and to assess the potential effect of food on its relative bioavailability. Methods The first study had an open, single-dose, three-treatment, three-period, six-sequence, randomised, crossover design with at least a five-day wash-out. The second study had an open, steady-state, two-treatment, two-period, two-sequence, randomised crossover design with at least a seven-day wash-out. Both studies contained 30 healthy subjects. Both enantiomers of tramadol and O-demethyl-tramadol (the only active metabolite of tramadol) were assayed in the plasma using an LC-MS/MS method. AUC∞, AUCt, Cmax, Tmax, and T1/2 were estimated. Statistical analysis was performed using univariate anova, the Wilcoxon nonparametric method or Friedman's nonparametric anova where appropriate. Results Tramadol had a significantly lower Cmax and longer Tmax than the conventional formulation. Thus, the mean (± sd) Cmax of tramadol were 646 ± 192 and 300 ± 94 ng ml−1 for Topalgic® 4 × 50mg and Tramadol LP 200 mg, respectively (95% confidence interval on the difference expressed as a percentage 42–51). AUC of tramadol from both formulations was comparable (similar AUC∞ and AUCt). Thus, the mean AUC∞ of (+/–)tramadol obtained after multiple dosing were 4611 ± 1944 and 5105 ± 2101 ngh ml−1 after Topalgic® 4 × 50mg and Tramadol LP 200 mg, respectively (95%CI 102–123%). We also demonstrate that the pharmacokinetics of the drug are not influenced by the intake of food. Thus, the mean AUC∞ of (+/–) tramadol were 5444 ± 1637 and 5169 ± 1580 ngh ml−1 after Tramadol LP 200 mg given in the fasting and fed states, respectively (95%CI = 88–103%). Conclusions The new sustained release form of tramadol

  1. Solid lipid extrudates as sustained-release matrices: the effect of surface structure on drug release properties.

    Science.gov (United States)

    Reitz, Claudia; Strachan, Clare; Kleinebudde, Peter

    2008-11-15

    The study focused on the structural characterization of sustained-release lipid matrices prepared by solid lipid extrusion. Drug-containing lipid extrudates were locally analyzed in order to identify differences between the chemical and structural composition of surface and core elements. Independent of the lipid the dissolution from the outer extrudate surfaces was slower compared with dissolution from surfaces prepared by cutting the extrudate. The burst effect was higher for the cross-sections indicating more drug was exposed on these surfaces. The release from glycerol trimyristate (Dynasan 114) extrudates was slower compared with glycerol palmitostearate (Precirol ATO 5) extrudates. By solid-state analysis using DSC, ATR-FTIR and SEM measurements the differences between surface material and core material could be attributed mainly to morphological differences. Chemical differences between the core and the outer surface were not relevant. The differences between the surfaces might be explained by the friction induced temperature increase during extrusion in the die plate. The obtained results and a proposed scheme were used to explain the influence of different formulation/processing parameters, such as drug particle size and milling on the drug dissolution behaviour. Small drug particles and intact extrudates are a means of minimizing the burst release.

  2. Dual-drug delivery by porous silicon nanoparticles for improved cellular uptake, sustained release, and combination therapy.

    Science.gov (United States)

    Wang, Chang-Fang; Mäkilä, Ermei M; Kaasalainen, Martti H; Hagström, Marja V; Salonen, Jarno J; Hirvonen, Jouni T; Santos, Hélder A

    2015-04-01

    Dual-drug delivery of antiangiogenic and chemotherapeutic drugs can enhance the therapeutic effect for cancer therapy. Conjugation of methotrexate (MTX) to porous silicon (PSi) nanoparticles (MTX-PSi) with positively charged surface can improve the cellular uptake of MTX and inhibit the proliferation of cancer cells. Herein, MTX-PSi conjugates sustained the release of MTX up to 96 h, and the released fragments including MTX were confirmed by mass spectrometry. The intracellular distribution of the MTX-PSi nanoparticles was confirmed by transmission electron microscopy. Compared to pure MTX, the MTX-PSi achieved similar inhibition of cell proliferation in folate receptor (FR) over-expressing U87 MG cancer cells, and a higher effect in low FR-expressing EA.hy926 cells. Nuclear fragmentation analysis demonstrated programmed cell apoptosis of MTX-PSi in the high/low FR-expressing cancer cells, whereas PSi alone at the same dose had a minor effect on cell apoptosis. Finally, the porous structure of MTX-PSi enabled a successful concomitant loading of another anti-angiogenic hydrophobic drug, sorafenib, and considerably enhanced the dissolution rate of sorafenib. Overall, the MTX-PSi nanoparticles can be used as a platform for combination chemotherapy by simultaneously enhancing the dissolution rate of a hydrophobic drug and sustaining the release of a conjugated chemotherapeutic drug.

  3. Novel Polyurethane Matrix Systems Reveal a Particular Sustained Release Behavior Studied by Imaging and Computational Modeling.

    Science.gov (United States)

    Campiñez, María Dolores; Caraballo, Isidoro; Puchkov, Maxim; Kuentz, Martin

    2017-07-01

    The aim of the present work was to better understand the drug-release mechanism from sustained release matrices prepared with two new polyurethanes, using a novel in silico formulation tool based on 3-dimensional cellular automata. For this purpose, two polymers and theophylline as model drug were used to prepare binary matrix tablets. Each formulation was simulated in silico, and its release behavior was compared to the experimental drug release profiles. Furthermore, the polymer distributions in the tablets were imaged by scanning electron microscopy (SEM) and the changes produced by the tortuosity were quantified and verified using experimental data. The obtained results showed that the polymers exhibited a surprisingly high ability for controlling drug release at low excipient concentrations (only 10% w/w of excipient controlled the release of drug during almost 8 h). The mesoscopic in silico model helped to reveal how the novel biopolymers were controlling drug release. The mechanism was found to be a special geometrical arrangement of the excipient particles, creating an almost continuous barrier surrounding the drug in a very effective way, comparable to lipid or waxy excipients but with the advantages of a much higher compactability, stability, and absence of excipient polymorphism.

  4. Studies on Commercially Available Sustained- or Controlled-Release Theophylline Products Commonly Used: Characterization of In-vitro Dissolution Properties and Kinetics

    Directory of Open Access Journals (Sweden)

    Omar H. El-Garhy

    2014-12-01

    Full Text Available Purpose: Theophylline (TP, is an one of the most popular drugs used in the therapy of the respiratory diseases such as chronic obstructive pulmonary disease (COPD and asthma under a variety of commercially brand names of oral sustained- or controlled-release products in the local market. The objective of this work is to endow an overview of type and dissolution characteristics of various sustained- or controlled-release products presently available. Method: The dissolution characteristics of TP from its commercially available sustained- or controlled-release products were studied in simulated gastric fluid for 2 hr and in simulated intestinal fluid for 8 hr using the USP dissolution apparatus with the paddle assembly. The kinetics of the dissolution profiles were determined by analyzing the dissolution data according to 4 kinetic equation models, namely; zero-order equation, first-order equation, Higuchi square root equation and Hixson-Crowell cube root law. Results: All the investigated commercially available TP products displayed good sustained-release patterns. The dissolution rate of TP from its commercially available capsule products was higher than that of TP commercially available tablet products. Further, the progress increase in the dissolution rate of TP from its commercially available capsule products along the dissolution period was more regular than that of TP commercially available tablet products. The kinetics study demonstrated that Zero-order and Hixon-Crowell’s models displayed sufficiently linearity with minimal differences between them suggesting that the release mechanism of TP from most of the investigated commercially available TP products may be a coupled release pattern between diffusion and dissolution mechanisms. Conclusion: The study demonstrated that most of the investigated commercial available TP products satisfied the requirements of good sustained-release products.

  5. Sustained drug release by contact lenses for glaucoma treatment-a review.

    Science.gov (United States)

    Carvalho, I M; Marques, C S; Oliveira, R S; Coelho, P B; Costa, P C; Ferreira, D C

    2015-03-28

    In the context of ocular pharmacology, there is a growing need for innovative delivery platforms for a convenient and sustained drug release into the eye, especially for chronic diseases that require the adoption of a strict insurmountable treatment regimen for a large part of the affected population, as in the case of glaucoma. Due to the large residence time of the contact lenses in the eye, its use for sustained drug delivery is quite promising. However, and despite the numerous therapeutic advantages arising from its use, the low affinity shown by most ophthalmic drugs for conventional contact lenses hinders the practical application of this technology. In this paper we elaborated a review of the various methods exploited so far to improve the contact lenses' characteristics as mechanisms for controlled and prolonged drug release for topical treatment of ocular diseases, with particular emphasis on the treatment of glaucoma.

  6. HPLC Method for the Determination of Tamsulosin Hydrochloride in Sustained Release Tablets

    Institute of Scientific and Technical Information of China (English)

    齐美玲; 王鹏; 耿颖姝; 顾峻岭

    2003-01-01

    The development and validation of an isocratic high performance liquid chromatographic method is described for the determination of tamsulosin hydrochloride in sustained release tablets. The determination was performed on a Diamonsil BDS C18 column with a mobile phase consisting of a mixture of acetonitrile, methanol and 0.5% phosphoric acid solution (20∶30∶50,V/V/V) at a flow rate of 1.0 mL/min. UV detection was made at 274 nm. The linear range for tamsulosin hydrochloride was 0.81-8.10 μg/mL. The mean recovery was 99.8% (SR=0.7%, n=9), and the precision was found to be 0.45% (n=9). The proposed method can be used for routine analysis of tamsulosin hydrochloride in sustained release tablets.

  7. Thermal and Isothermal Methods in Development of Sustained Release Dosage Forms of Ketorolac Tromethamine

    Directory of Open Access Journals (Sweden)

    Dimple Chopra

    2008-01-01

    Full Text Available Differential scanning calorimetry (DSC is a rapid and convenient and conclusive method of screening drug-polymer blend during preformulation studies as it allows polymer incompatibility to be established instantaneously. Various batches of matrix tablets of ketorolac tromethamine (KTM with a series of compatible polymers were prepared. Batches of tablets which gave desired sustained release profile were subjected to stability testing according to ICH guidelines. The analysis for drug content was done using high performance liquid chromatography (HPLC method. The results revealed that there was no statistically significant change in drug content after storage of matrix tablets at elevated temperature of 40°C and 75% relative humidity. From our study we conclude that with careful selection of different polymers and their combinations, a stable sustained release oral dosage form of ketorolac tromethamine can be achieved.

  8. Development and In Vitro Characterization of Sustained Release Pellets of Venlafaxine Hydrochloride

    Directory of Open Access Journals (Sweden)

    P.REMYA

    2012-05-01

    Full Text Available The present study was undertaken with development and in-vitro characterization of sustained release pellets of venlafaxine hydrochloride by wruster process technique .which release the drug in sustained manner over a period of 20 hours. The different viscosity grades of polymers are HPMC-E6, Ethyl cellulose 7cps, MCC-101 were preparation of granules or pellets by wurster coating .The granules were prepared and evaluated for Angle of repose, bulk density, tapped density, cars index, moisture content, stability studies and dissolution studies were carried out. Formulation f1 and f2 can be considered as an optimized formulation for disperse the drug freely in GIT tract of venlafaxine HCl for getting more bioavailability.

  9. Evaluation of Mimosa pudica seed mucilage as sustained-release excipient.

    Science.gov (United States)

    Singh, Kuldeep; Kumar, Ashok; Langyan, Naresh; Ahuja, Munish

    2009-01-01

    The present study was conducted to investigate the sustained-release properties of Mimosa pudica seed mucilage. Matrix tablets of diclofenac sodium containing different proportions of mucilage and dibasic calcium phosphate as diluent were formulated by wet granulation method. The tablets had uniform physical appearance, average weight, drug content, and adequate hardness. The results of in vitro release conducted using USP type II dissolution rate apparatus, in a dissolution media comprising of 900 mL of 0.1 N HCl for 2 h followed by phosphate buffer (pH 6.8) for 24 h at 37 degrees C and 50 rpm, revealed that as the proportion of mucilage in the matrix was increased there was a corresponding decrease in the release of drug. Further, the matrix tablets were found to release the drug following Higuchi square root release kinetics, with the mechanism of release being diffusion for tablets containing higher proportion of mucilage and a combination of matrix erosion and diffusion for tablets containing smaller proportion of mucilage. 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. The SEM photomicrographs showed gelling structures in tablets containing higher percentage of mucilage, while both pores and gelling structures were present on the surface of tablets containing smaller proportion of mucilage and commercial formulation. On comparative evaluation, the dissolution profile from formulation containing mucilage to drug in the proportion of 1:40 was found to be similar to the commercial sustained-release formulation of diclofenac.

  10. H2-antagonist derangement of the kinetics of sustained-release oral theophylline.

    Science.gov (United States)

    Dal Negro, R; Turco, P; Zoccatelli, O; Trevisan, F; Pomart, C

    1985-06-01

    The authors have evaluated the interference of the H2-antagonists cimetidine and ranitidine with the elimination kinetics of sustained-release anhydrous theophylline, administered per os at the dose of 300 mg b.i.d. in two randomly selected groups of patients suffering from chronic obstructive lung disease. The plasma theophylline trends (obtained over a 12-hour period) were compared in the two groups in basal conditions (on reaching the theophylline steady state) and after 8 days treatment with cimetidine or ranitidine. In addition, the bronchodilator effect of theophylline was evaluated in these experimental conditions by means of FEV1 measurements. Simultaneous administration of ranitidine produced no changes in theophylline elimination, and the bronchodilator effect of theophylline proved both substantial and systematic in the patients treated with this H2-antagonist. On the other hand, the patients treated with cimetidine showed a marked, systematic increase in theophylline plasma levels, even exceeding the upper limit of its known therapeutic range in 4 cases. Despite this, no evidence of a bronchodilator effect was found in the cimetidine-treated patients, while significant effects attributable to theophylline toxicity were observed in the 4 cases with excessive theophylline plasma levels. The simultaneous administration of cimetidine in patients treated with sustained-release anhydrous theophylline thus proved capable of seriously undermining the strategy of theophylline usage precisely on account of the high degree of bioavailability of theophylline in the sustained-release formulation.

  11. HPLC determination and pharmacokinetics of sustained-release bupropion tablets in dogs.

    Science.gov (United States)

    Zhang, Dandan; Yuan, Bo; Qiao, Mingxi; Li, Famei

    2003-09-19

    The pharmacokinetics and bioequivalency of a newly developed sustained-release bupropion tablet was studied in six dogs after single oral administration and compared with a regular tablet (RT) in randomized two-period crossover design. A sensitive and rapid HPLC method was developed and validated for the quantitative determination of bupropion in dog plasma. The compound and the internal standard (I.S.) (hydroxyethylfludiazepam) were extracted from the plasma samples by liquid-liquid extraction. The extracts were analyzed by a reversed-phase HPLC with 50 mmol/l phosphate buffer (pH 5.5)-methanol (45:55, v/v) as the eluent. The assay was specific for bupropion. The calibration curves were linear in the range between 1 and 750 ng/ml. The validated lower limit of quantification was 1 ng/ml. The overall precision (expressed as R.S.D.) of quality controls were within 15%. The method was successfully applied to the bioequivalency study of bupropion in the two formulations. The Cmax of sustained-release tablet (ST) was significantly lower than that of the RT and the Tmax was significantly longer than that of the RT (P<0.05). The relative bioavailability of the ST was (99.1+/-1.51)%, the results of ANOVA and two one sided tests indicated that the new ST exhibited good sustained release properties and was bioequivalent to the RT.

  12. Polymer grafted-magnetic halloysite nanotube for controlled and sustained release of cationic drug.

    Science.gov (United States)

    Fizir, Meriem; Dramou, Pierre; Zhang, Kai; Sun, Cheng; Pham-Huy, Chuong; He, Hua

    2017-11-01

    In this research, novel polymer grafted-magnetic halloysite nanotubes with norfloxacin loaded (NOR-MHNTs) and controlled-release, was achieved by surface-initiated precipitation polymerization. The magnetic halloysite nanotubes exhibited better adsorption of NOR (72.10mgg(-1)) compared with the pristine HNTs (30.80mgg(-1)). Various parameters influencing the drug adsorption of the MHNTs for NOR were studied. Polymer grafted NOR-MHNTs has been designed using flexible docking in computer simulation to choose optimal monomers. NOR-MHNTs/poly (methacrylic acid or acrylamide-co-ethylene glycol dimethacrylate) nanocomposite were synthesized using NOR-MHNTs, methacrylic acid (MAA) or acrylamide (AM), ethylene glycol dimethacrylate (EGDMA) and AIBN as nanotemplate, monomers, cross linker and initiator, respectively. The magnetic nanocomposites were characterized by FTIR, TEM, XRD and VSM. The magnetic nanocomposites show superparamagnetic property and fast magnetic response (12.09emug(-1)). The copolymerization of monomers and cross linker led to a better sustained release of norfloxacin (>60h) due to the strong interaction formed between monomers and this cationic drug. The cumulative release rate of NOR is closely related to the cross linker amount. In conclusion, combining the advantages of the high adsorption capacity and magnetic proprieties of this biocompatible clay nanotube and the advantages of polymer shell in the enhancement of controlled-sustained release of cationic drug, a novel formulation for the sustained-controlled release of bioactive agents is developed and may have considerable potential application in targeting drug delivery system. Copyright © 2017. Published by Elsevier Inc.

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

    Indian Academy of Sciences (India)

    JAYESH S PATIL; PRITAM B PATIL; PRAVIN SONAWANE; JITENDRA B NAIK

    2017-04-01

    The aim of this study was to develop sustained-release glyburide-loaded silica nanoparticles. Silica nanoparticles were synthesized by the sol–gel method using tetra-ethyl ortho-silane as a precursor. Glyburide was successfully entrapped in synthesized silica nanoparticles. To identify the effect of independent variables (concentration of silica and concentration of glyburide) on encapsulation efficiency and drug release (dependent variables), 3$^2$ (three level-two factors) response surface methodology was employed. Silica nanoparticles and glyburide-loaded silica nanoparticles were characterized by scanning electron microscopy, BET surface area, X-ray diffraction andFourier transformed infrared spectroscopy. The optimum values of encapsulation efficiency and drug release were 70.21 and 87.8% over 24 h, respectively; these values agree well with predicted values obtained by response surfacemethodology. Glyburide-loaded silica nanoparticles were successfully prepared without any incompatibility and seem to be promising for sustained-release drug delivery application and better patient compliance.

  14. FORMULATION DEVELOPMENT AND IN-VITRO EVALUATION OF SUSTAINED RELEASE MATRIX TABLETS OF SALBUTAMOL SULPHATE

    Directory of Open Access Journals (Sweden)

    AMITAVA GHOSH KOUSHIK SEN GUPTA

    2013-09-01

    Full Text Available ABSTRACT: The objective of the present study was to develop salbutamol sulphate matrix tablets, sustained release dosage form, for the treatment of Chronic Obstructive Pulmonary Disease (COPD. Simultaneous equations were formed to calculate the concentration values of Salbutamol sulphate and drug compatibility study was performed through Infrared spectroscopy. The matrix tablets were prepared by wet granulation method using two hydrophobic polymers such as Ethyl cellulose and Acrycoat S-100 in varying ratios. The granules exhibited satisfactory rheological demeanor. All the seven tablet formulations showed acceptable pharmacotechnical properties and complied with the in-house specifications for tested parameters. The results of formulation F-4 (Ethyl cellulose and Acrycoat in 2:1 ratio could extend the release of Salbutamol sulphate up to 12 hr and was found comparable to marketed sustained release products. Model fitting analysis (Zero order, Higuchi and Korsmeyer-Peppas model for all the formulations were performed and it was seen that all the formulations predominantly follow the Higuchi model. While comparing with the ‘n’ values of all the formulations of Korsmeyer-Peppas model, Fickian/Diffusion controlled release was observed in case of F-4 and F-5, whereas for the other formulations non-Fickian transport was observed.

  15. 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

  16. Development and in-vitro evaluation of sustained-release meclofenamic acid microspheres.

    Science.gov (United States)

    Khidr, S H; Niazy, E M; el-Sayed, Y M

    1998-01-01

    Meclofenamic acid (MFA) sustained-release microspheres were prepared by the solvent evaporation method using cellulose propionate (CP) polymer and acetone as the polymer solvent. Polyethylene glycol (PEG) was used as a channelling agent to improve the release properties of MFA at 1:2:1 drug to polymer to PEG ratio. The microspheres prepared at three different speeds (600, 800 and 1000 rpm) were characterized with regard to their surface morphology, average drug content, particle size distribution and release profiles in phosphate buffer, pH 8.0 at 37 degrees C. The microspheres were stored under accelerated conditions for 3 months and the effect of storage on the different characteristics was studied. Spherical particles with essentially smooth surface and few residual drug crystals on the surface were formed. Smaller particles were formed at higher agitation speeds. The release rate of MFA from these microspheres was not affected by the molecular weight of CP polymer. PEG 2000 was found to have a more enhancing effect on the rate of the release than PEG 4000. The physical properties of the microspheres and their release characteristics were not altered by storing the product at 40 degrees C/80% relative humidity (R.H.) for 3 months.

  17. [Sustained release of the antitumor drug paclitaxel from poly(3-hydroxybutyrate)-based microspheres].

    Science.gov (United States)

    Bonartsev, A P; Iaovlev, S G; Filatova, E V; Soboleva, G M; Makhina, T K; Bonartseva, G A; Shaĭtan, K V; Popov, V O; Kirpichnikov, M P

    2011-01-01

    Development of systems of medicines with sustained action on the basis of biodegradable polymers is a promising trend in modem pharmacology. Polyhydroxyalkanoates (POA) attract increasing attention due to their biodegradability and high biocompatibility, which make them suitable for development of novel drug dosage forms. We obtained microspheres on the basis of poly(3-hydroxybutyrate) (PHB) loaded with the antitumor drug paclitaxel. Morphology, drug release kinetics and effect on tumor cells in vitro of microspheres were studied. The data on the kinetics of drug release, biocompatibility and biological activity of the biopolymer microspheres in vitro showed that the studied system of prolonged drug release had lower toxicity and higher efficiency compared to the traditional dosage forms of paclitaxel.

  18. Formulation and evaluation of a sustained-release tablets of metformin hydrochloride using hydrophilic synthetic and hydrophobic natural polymers

    Directory of Open Access Journals (Sweden)

    K J Wadher

    2011-01-01

    Full Text Available Metformin hydrochloride has relatively short plasma half-life, low absolute bioavailability. The need for the administration two to three times a day when larger doses are required can decrease patient compliance. Sustained release formulation that would maintain plasma level for 8-12 h might be sufficient for daily dosing of metformin. Sustained release products are needed for metformin to prolong its duration of action and to improve patient compliances. The overall objective of this study was to develop an oral sustained release metformin hydrochloride tablet by using hydrophilic Eudragit RSPO alone or its combination with hydrophobic natural polymers Gum copal and gum damar as rate controlling factor. The tablets were prepared by wet granulation method. The in vitro dissolution study was carried out using USP 22 apparatus I, paddle method and the data was analysed using zero order, first order, Higuchi, Korsmeyer and Hixson-Crowell equations. The drug release study revealed that Eudragit RSPO alone was unable to sustain the drug release. Combining Eudragit with gum Copal and gum Damar sustained the drug release for more than 12 h. Kinetic modeling of in vitro dissolution profiles revealed the drug release mechanism ranges from diffusion controlled or Fickian transport to anomalous type or non-Fickian transport. Fitting the in vitro drug release data to Korsmeyer equation indicated that diffusion along with erosion could be the mechanism of drug release.

  19. Formulation and evaluation of a sustained-release tablets of metformin hydrochloride using hydrophilic synthetic and hydrophobic natural polymers.

    Science.gov (United States)

    Wadher, K J; Kakde, R B; Umekar, M J

    2011-03-01

    Metformin hydrochloride has relatively short plasma half-life, low absolute bioavailability. The need for the administration two to three times a day when larger doses are required can decrease patient compliance. Sustained release formulation that would maintain plasma level for 8-12 h might be sufficient for daily dosing of metformin. Sustained release products are needed for metformin to prolong its duration of action and to improve patient compliances. The overall objective of this study was to develop an oral sustained release metformin hydrochloride tablet by using hydrophilic Eudragit RSPO alone or its combination with hydrophobic natural polymers Gum copal and gum damar as rate controlling factor. The tablets were prepared by wet granulation method. The in vitro dissolution study was carried out using USP 22 apparatus I, paddle method and the data was analysed using zero order, first order, Higuchi, Korsmeyer and Hixson-Crowell equations. The drug release study revealed that Eudragit RSPO alone was unable to sustain the drug release. Combining Eudragit with gum Copal and gum Damar sustained the drug release for more than 12 h. Kinetic modeling of in vitro dissolution profiles revealed the drug release mechanism ranges from diffusion controlled or Fickian transport to anomalous type or non-Fickian transport. Fitting the in vitro drug release data to Korsmeyer equation indicated that diffusion along with erosion could be the mechanism of drug release.

  20. 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.

  1. 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.

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

    Science.gov (United States)

    Zeng, Shuguang; Ye, Manwen; Qiu, Junqi; Fang, Wei; Rong, Mingdeng; Guo, Zehong; Gao, Wenfen

    2015-01-01

    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 entrapped BSA on the 1st day and cumulatively released 75.20%±2.52%, 79.16%±4.31%, and 89.04%±4.68% in 21 days, respectively. The pure CS microspheres prepared in the presence of 10 mg of BSA burst release 39.53%±1.76% of BSA on the 1st day and cumulatively released 83.57%±2.33% of the total encapsulated BSA in 21 days. The SF-CS composite microspheres exhibited higher sustained release than did the pure CS microspheres, and thus these composite

  3. Interfacial modification of clay nanotubes for the sustained release of corrosion inhibitors.

    Science.gov (United States)

    Joshi, Anupam; Abdullayev, Elshad; Vasiliev, Alexandre; Volkova, Olga; Lvov, Yuri

    2013-06-18

    Long-lasting anticorrosive coatings for steel have been developed on the basis of halloysite nanotubes loaded with three corrosion inhibitors: benzotriazole, mercaptobenzothiazole, and mercaptobenzimidazole. The inhibitors' loaded tubes were admixed at 5-10 wt % to oil-based alkyd paint providing sustained agent release and corrosion healing in the coating defects. The slow 20-30 h release of the inhibitors at defect points caused a remarkable improvement in the anticorrosion efficiency of the coatings. Further time expansion of anticorrosion agent release has been achieved by the formation of release stoppers at nanotube ends with urea-formaldehyde copolymer and copper-inhibitor complexation. The corrosion protection efficiency was tested on ASTM A366 steel plates in a 0.5 M NaCl solution with the microscanning of corrosion current development by microscopy inspection and studying paint adhesion. The best protection was found using halloysite/mercaptobenzimidazole and benzotriazole inhibitors. Stopper formation with urea-formaldehyde copolymer provided an additional increase in corrosion efficiency as a result of the longer release of inhibitors.

  4. Preparation and evaluation of novel metronidazole sustained release and floating matrix tablets.

    Science.gov (United States)

    Asnaashari, Solmaz; Khoei, Nazaninossadat Seyed; Zarrintan, Mohammad Hosein; Adibkia, Khosro; Javadzadeh, Yousef

    2011-08-01

    In the present study, metronidazole was used for preparing floating dosage forms that are designed to retain in the stomach for a long time and have developed as a drug delivery system for better eradication of Helicobacter Pylori in peptic ulcer diseases. For this means, various formulations were designed using multi-factorial design. HPMC, psyllium and carbopol in different concentrations were used as floating agents, and sodium bicarbonate was added as a gas-forming agent. Hardness, friability, drug loading, floating ability and release profiles as well as kinetics of release were assessed. Formulations containing HPMC as filler showed prolonged lag times for buoyancy. Adding psyllium to these formulations had reduced relative lag times. Overall, selected formulations were able to float immediately and showed buoyancy for at least 8?h. Meanwhile, sustained profiles of drug release were also obtained. Kinetically, among the 10 assessed models, the release pattern of metronidazole from the tablets fitted best to Power law, Weibull and Higuchi models in respect overall to mean percentage error values of 3.8, 4.73 and 5.77, respectively, for calcium carbonate-based tablets and, 2.95, 6.39 and 3.9, respectively, for calcium silicate-based tablets. In general, these systems can float in the gastric condition and control the drug release from the tablets.

  5. Preparation and in-vitro evaluation of sustained-release metoclopramide hydrochloride microspheres.

    Science.gov (United States)

    Khidr, S H; Niazy, E M; el-Sayed, Y M

    1995-01-01

    Sustained-release metoclopramide microspheres were successfully prepared using cellulose propionate polymer at 1:2 drug to polymer ratio employing solvent evaporation technique and using acetone as the polymer solvent. The prepared microspheres at three stirring speeds were characterized with regard to their drug content, particle size distribution, surface topography using SEM and their release profiles at two different pHs at 37 degrees C. The surface of all samples was smooth with very few irregular elevations or depressions. The average particle size decreases as the rotational speed increases and was found to be 1320, 774 and 345 microns at 600, 900 and 1200 rpm, respectively. The average % drug entrapped was found to be 90.5, 100.1 and 60.0% at 600, 900 and 1200 rpm, respectively. Small differences in the release rate were observed due to different rotation speeds with an apparent lower dissolution for batches produced at 1200 rpm probably due to the properties of the coat. The effect of storage under accelerated conditions for 10 weeks on the release characteristics of these microspheres was also studied. The release properties of the microspheres did not change after storing them at 40 degrees C/80% relative humidity for 10 weeks.

  6. Demonstrating the advantages of novel exploration strategies for sustainable managed aquifer recharge operation

    Science.gov (United States)

    Vienken, Thomas; Werban, Ulrike; Cisotto, Alberto; Ferri, Michele; Tippelt, Thomas; Dietrich, Peter

    2016-04-01

    Water scarcity and drought have led to a strong decline of water availability in many semiarid regions with resulting ecological and economic impacts. Managed aquifer recharge (MAR) represents a promising technique to replenish water resources, and in combination with awareness raising, is an important step towards sustainable water management. However, choice of type and positioning large scale MAR infrastructure, e.g. water infiltration basins and trenches, is challenging as it requires a detailed understanding of the subsurface. In addition, clogging effects can lead to a strong decrease of MAR efficiency. Hence, MAR site maintenance is in many cases time intensive and costly. In our work we demonstrate the successful application of novel strategies for enhanced MAR site characterization at the Schiavon Forested Infiltration Site, Italy.

  7. FORMULATION AND EVALUATION OF SUSTAINED RELEASE LIQUISOLID TABLETS OF METOPROLOL SUCCINATE

    Directory of Open Access Journals (Sweden)

    Jarag Ravindra Jagannath

    2013-03-01

    Full Text Available Liquisolid technique is the novel concept of drug delivery via the oral route. This technique is applied to poorly water soluble, water insoluble or liphophilic drugs. According to the new formulation method of liquisolid compacts, liquid medications such as solutions or suspensions of water insoluble drugs in suitable non-volatile vehicles can be converted into acceptably flowing and compressible powders by blending with selected powder excipients. The present research endeavor is directed towards the development of liquisolid compact for the production of sustained release tablet of water-soluble Metoprolol succinate. Liquisolid compacts were prepared by using Tween 80 as the liquid vehicle or non-volatile solvent, Avicel PH 102 as absorbing carrier and Aerosil 200 as adsorbing coating material. The prepare dliquisolid systems were evaluated for their micromeretic properties and possible drug-excipients interactions. P-XRD analysis confirmed that no change in crystallinity of Metoprolol succinate Liquisolid compacts. The DSC and IR spectra analysis study ruled out no any significant interaction between the drug and excipients used in preparation of Metoprolol succinate Liquisolid compacts. The tableting properties were falling within acceptable limits. The in vitro dissolution study confirmed reduction in drug release from Liquisolid compacts compared to conventional matrix tablet, in-vivo study was carried out to check the plasma drug concentration. Tween 80 has plasticizer effect by which it can reduce the glass transition temperature of polymer and impart flexibility in sustaining the release of drug from liquisolid matrices. The results showed that wet granulation had a remarkable impact on the release rate of Metoprolol succinate from liquisolid compacts, reducing the release rate of drug from liquisolid compacts.

  8. An Epichlorohydrin-Crosslinked Semi-Interpenetrating GG-PEO Network as a Xerogel Matrix for Sustained Release of Sulpiride

    National Research Council Canada - National Science Library

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

    2014-01-01

    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...

  9. Injectable and implantable sustained release naltrexone in the treatment of opioid addiction.

    Science.gov (United States)

    Kunøe, Nikolaj; Lobmaier, Philipp; Ngo, Hanh; Hulse, Gary

    2014-02-01

    Sustained release technologies for administering the opioid antagonist naltrexone (SRX) have the potential to assist opioid-addicted patients in their efforts to maintain abstinence from heroin and other opioid agonists. Recently, reliable SRX formulations in intramuscular or implantable polymers that release naltrexone for 1-7 months have become available for clinical use and research. This qualitative review of the literature provides an overview of the technologies currently available for SRX and their effectiveness in reducing opioid use and other relevant outcomes. The majority of studies indicate that SRX is effective in reducing heroin use, and the most frequently studied SRX formulations have acceptable adverse events profiles. Registry data indicate a protective effect of SRX on mortality and morbidity. In some studies, SRX also seems to affect other outcomes, such as concomitant substance use, vocational training attendance, needle use, and risk behaviour for blood-borne diseases such as hepatitis or human immunodeficiency virus. There is a general need for more controlled studies, in particular to compare SRX with agonist maintenance treatment, to study combinations of SRX with behavioural interventions, and to study at-risk groups such as prison inmates or opioid-addicted pregnant patients. The literature suggests that sustained release naltrexone is a feasible, safe and effective option for assisting abstinence efforts in opioid addiction. © 2012 The Authors. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.

  10. Development of an inhaled sustained release dry powder formulation of salbutamol sulphate, an antiasthmatic drug

    Directory of Open Access Journals (Sweden)

    C Kumaresan

    2016-01-01

    Full Text Available The present research was aimed to develop and characterize a sustained release dry powder inhalable formulation of salbutamol sulphate. The salbutamol sulphate microparticles were prepared by solvent evaporation method using biodegradable polymer poly (D,L-lactic-co-glycolic acid to produce salbutamol sulphate microparticle mixed with carrier respirable grade lactose for oral inhalation of dry powder. The drug content were estimated to produce 1 mg sustained release salbutamol sulphate per dose. Total four formulations K1, K2, K3 and K4 were prepared with 1:1, 1:2, 1:3, 1:4 ratio of salbutamol sulphate:poly (D,L-lactic-co-glycolic acid. The developed formulations were studied for physicochemical properties, in vitro drug relase and Anderson cascade impaction studies. The prepared formulations effectively releases drug for 12 h in diffusion bag studies. Based on dissolution performance the 1:1 ratio of salbutamol sulphate:poly (D,L-lactic-co-glycolic acid produces in vitrorelease 92.57% at 12 h and having particle size of microparticles (D0.5μm 5.02±0.6 and the pulmonary deposition of dry powder 34.5±3.21 (respiratory fraction in percentage.

  11. Sustained Release of Antibacterial Lipopeptides from Biodegradable Polymers against Oral Pathogens

    Science.gov (United States)

    Eckhard, Lea H.; Houri-Haddad, Yael; Sol, Asaf; Zeharia, Rotem; Shai, Yechiel; Beyth, Shaul; Domb, Abraham J.

    2016-01-01

    The development of antibacterial drugs to overcome various pathogenic species, which inhabit the oral cavity, faces several challenges, such as salivary flow and enzymatic activity that restrict dosage retention. Owing to their amphipathic nature, antimicrobial peptides (AMPs) serve as the first line of defense of the innate immune system. The ability to synthesize different types of AMPs enables exploitation of their advantages as alternatives to antibiotics. Sustained release of AMPs incorporated in biodegradable polymers can be advantageous in maintaining high levels of the peptides. In this study, four potent ultra-short lipopeptides, conjugated to an aliphatic acid chain (16C) were incorporated in two different biodegradable polymers: poly (lactic acid co castor oil) (PLACO) and ricinoleic acid-based poly (ester-anhydride) (P(SA-RA)) for sustained release. The lipopeptide and polymer formulations were tested for antibacterial activity during one week, by turbidometric measurements of bacterial outgrowth, anti-biofilm activity by live/dead staining, biocompatibility by hemolysis and XTT colorimetric assays, mode of action by fluorescence-activated cell sorting (FACS) and release profile by a fluorometric assay. The results show that an antibacterial and anti-biofilm effect, as well as membrane disruption, can be achieved by the use of a formulation of lipopeptide incorporated in biodegradable polymer. PMID:27606830

  12. FORMULATION AND EVALUATION OF SUSTAINED RELEASE TABLET OF DILTIAZEM HYDROCHLORIDE BY MELT GRANULATION TECHNOLOGY

    Directory of Open Access Journals (Sweden)

    Birajdar Ganesh

    2013-07-01

    Full Text Available The objective behind present study was to formulate and evaluate sustained release tablet of Diltiazem hydrochloride by using different polymers by melt granulation technology and to study the effect of various concentrations of polymers on release rate from tablet. Tablets were prepared using bees wax, carnauba wax, paraffin wax as release ratardent polymers. The drug and excipient compatibility study was done by FTIR method using KBr pellet method. The granules prepared by melt granulation technique evaluated for characterization such as bulk density, tapped density, hausners ratio, angle of repose, cars index all granules shows good flow property. The tablet of Diltiazem HCL evaluated for characterization such as hardness, friability, weight variation and content uniformity all tablets shows sufficient hardness and friability shows that tablets are having sufficient strength. All results were satisfactory. The in vitro drug release studies for the prepared formulation were conducted for a period of 12 h using an EDT 08LX dissolution tester USP Type - II apparatus (rotating paddle set at 100 rpm and a temperature of 37 ± 0.5°C formulation was placed in the 900 ml of the medium. For first 2 h tablet was placed in 1.2 pH acidic medium which was replaced with 7.4 pH phosphate buffer for remaining 10 h. From the dissolution study and comparative graph it was concluded that increase in concentration of wax shows decrease in drug release from tablet. Batch F3 shows 99.84 % drug release at 12 h. In vitro release data of optimized formulations (Batch F3 was fitted to various kinetic models like zero order, first order, Higuchi, korsmeyer-peppas and pass Higuchi model as it has highest r2 value (0.955 among all models.

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

    Science.gov (United States)

    Ngo, Vuong Duy; Luu, Thinh Duc; Van Vo, Toi; Tran, Van-Thanh; Duan, Wei; Tran, Phuong Ha-Lien; Tran, Thao Truong-Dinh

    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 pH6.8 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.

  14. Formulation and Evaluation of a Sustained-Release Tablets of Metformin Hydrochloride Using Hydrophilic Synthetic and Hydrophobic Natural Polymers

    OpenAIRE

    K J Wadher; Kakde, R. B.; M J Umekar

    2011-01-01

    Metformin hydrochloride has relatively short plasma half-life, low absolute bioavailability. The need for the administration two to three times a day when larger doses are required can decrease patient compliance. Sustained release formulation that would maintain plasma level for 8-12 h might be sufficient for daily dosing of metformin. Sustained release products are needed for metformin to prolong its duration of action and to improve patient compliances. The overall objective of this study ...

  15. Development and Evaluation of Sustained Release Tablet of Betahistine Hydrochloride Using Ion Exchange Resin Tulsion T344

    OpenAIRE

    Wagh, Vijay D.; Pawar, Nilesh

    2012-01-01

    An attempt was made to sustain the release of Betahistine hydrochloride by complexation technique using strong cation-exchange resin, Tulsion T344. The drug loading onto ion-exchange resin was optimized for mixing time, activation, effect of pH, swelling time, ratio of drug : resin, and temperature. The resinate was evaluated for micromeritic properties and characterized using XRPD and IR. For resinate sustained release tablets were formulated using hydoxypropyl methylcellulose K100M. The tab...

  16. Development and Demonstration of Sustainable Surface Infrastructure for Moon/Mars Exploration

    Science.gov (United States)

    Sanders, Gerald B.; Larson, William E.; Picard, Martin

    2011-01-01

    For long-term human exploration of the Moon and Mars to be practical, affordable, and sustainable, future missions must be able to identify and utilize resources at the site of exploration. The ability to characterize, extract, processes, and separate products from local material, known as In-Situ Resource Utilization (ISRU), can provide significant reductions in launch mass, logistics, and development costs while reducing risk through increased mission flexibility and protection as well as increased mission capabilities in the areas of power and transportation. Making mission critical consumables like propellants, fuel cell reagents and life support gases, as well as in-situ crew/hardware protection and energy storage capabilities can significantly enhance robotic and human science and exploration missions, however other mission systems need to be designed to interface with and utilize these in-situ developed products and services from the start or the benefits will be minimized or eliminated. This requires a level of surface and transportation system development coordination not typically utilized during early technology and system development activities. An approach being utilized by the US National Aeronautics and Space Administration and the Canadian Space Agency has been to utilize joint analogue field demonstrations to focus technology development activities to demonstrate and integrate new and potentially game changing. mission critical capabilities that would enable an affordable and sustainable surface infrastructure for lunar and Mars robotic and human exploration. Two analogue field tests performed in November 2008 and February 2010 demonstrated first generation capabilities for lunar resource prospecting, exploration site preparation, and oxygen extraction from regolith while initiating integration with mobility, science, fuel cell power, and propulsion disciplines. A third analogue field test currently planned for June 2012 will continue and expand

  17. Surelease or organic solution of ethylcellulose in preparation of sustained release theophylline micromatrices or matrices using spray drying technique.

    Science.gov (United States)

    Afrasiabi Garekani, Hadi; Sedighi, Samira; Sadeghi, Fatemeh

    2015-03-01

    This study evaluated ethylcellulose (EC) in two forms in preparation of sustained release theophylline microparticles using spray drying. Spray dried (SD) samples at different drug:polymer ratios were prepared using Surelease (SDaq) or organic solutions of ethylcellulose (SDor). Properties of particles (yield, particle morphology, size distribution and release profiles) were examined. Differential scanning calorimetry (DSC) and infrared spectroscopy (IR) studies were performed to track polymorphic changes and/or drug polymer interactions. SD samples were compressed and crushing strengths and release profiles were determined. The yields were in the range of 55-70%. The SD samples were nearly spherical with numerous fine particles attached to their surfaces. The SDor samples showed the smallest particle size. No polymorphism or drug-polymer interaction was observed. Uncompressed SDaq samples showed inadequate sustained release of drug compared to SDor samples. Surelease content did not affect drug release from SDaq samples. Tablets prepared from SDaq were softer and showed some plasticity, while those prepared from SDor exhibited higher crushing strengths. Tablets prepared from SDaq showed sustained release properties while the release of drug from compressed SDor samples were too slow. Overall Surelease was unable to sustain release of theophylline from SDaq microparticles, however, in compacted form showed more appropriate drug release than compacted SDor.

  18. Corticotropin releasing factor impairs sustained attention in male and female rats.

    Science.gov (United States)

    Cole, Robert D; Kawasumi, Yushi; Parikh, Vinay; Bangasser, Debra A

    2016-01-01

    Stressful life events and stress-related psychiatric disorders impair sustained attention, the ability to monitor rare and unpredictable stimulus events over prolonged periods of time. Despite the link between stress and attentional disruptions, the neurobiological basis for stress regulation of attention systems remains underexplored. Here we examined whether corticotropin releasing factor (CRF), which orchestrates stress responses and is hypersecreted in patients with stress-related psychiatric disorders, impairs sustained attention. To this end, male and female rats received central infusions of CRF prior to testing on an operant sustained attention task (SAT), where rats were trained to discriminate signaled from non-signaled events. CRF caused a dose-dependent decrease in SAT performance in both male and female rats. Females were more impaired than males following a moderate dose of CRF, particularly during the middle part of the session. This sex difference was moderated by ovarian hormones. Females in the estrous cycle stage characterized by lower ovarian hormones had a greater CRF-induced attentional impairment than males and females in other cycle stages. Collectively, these studies highlight CRF as a critical stress-related factor that can regulate attentional performance. As sustained attention subserves other cognitive processes, these studies suggest that mitigating high levels of CRF in patients with stress-related psychiatric disorders may ameliorate their cognitive deficits.

  19. New co-polymer zwitterionic matrices for sustained release of verapamil hydrochloride.

    Science.gov (United States)

    Kostova, Bistra; Rachev, Dimitar

    2007-12-01

    Stable co-polymer [vinyl acetate-co-3-dimethyl(methacryloyloxyethyl) ammonium propane sulfonate, p(VA-co-DMAPS)] latex of different compositions has been synthesized for the first time by emulsifier-free emulsion copolymerization. The unusual >overshooting< behavior of the co-polymer tablets has been explained by the formation of specific clusters from the opposite oriented dipoles-zwitterionic species. The change of their concentration with the DMAPS unit fraction (mDMAPS), pH and ionic strength has been considered responsible for the differences observed in the swelling kinetics. The results obtained prove that mDMAPS and ionic strength could be used to control the swelling degree of the p(VA-co-DMAPS) matrices and their sustained drug delivery. In this way, p(VA-co-DMAPS) matrices could be effectively used to control the sustained release of drugs with basic properties like verapamil hydrochloride from model tablets.

  20. Development of a sustained-release recombinant human growth hormone formulation.

    Science.gov (United States)

    Kwak, H H; Shim, W S; Choi, M K; Son, M K; Kim, Y J; Yang, H C; Kim, T H; Lee, G I; Kim, B M; Kang, S H; Shim, C K

    2009-07-20

    Recombinant human growth hormone (rhGH) therapy for short stature must be administered as a daily injection because of its poor bioavailability and short half-life. In the present study, a sustained-release formulation of rhGH (SR-rhGH), DA-3003, was prepared using double emulsion solvent evaporation with poly(D,L-lactide-co-glycolide) (PLGA), zinc oxide and hydroxypropyl-beta-cyclodextrin (HPCD) as the release modulator, stabilizer, and aggregation-prevention agent, respectively. After a single administration of DA-3003, the elevated concentration of rhGH in plasma was sustained for 14 days in rats and 28 days in monkeys. The plasma concentration of insulin-like growth factor-1 (IGF-I) and insulin-like growth factor binding protein-3 (IGFBP-3), which are pharmacodynamic markers of rhGH administration, increased and remained elevated for approximately 28 days in monkeys. Monkeys administered DA-3003 did not develop antibodies to hGH, indicating safety of the SR-rhGH formulation comparable to that observed with daily rhGH injections (Growtropin II). There were no significant differences in efficacy between Growtropin II (daily dose of 5 microg/animal for 14 days) and DA-3003 (weekly dose of 35 microg/animal for 14 days with a dosing interval of a week) in hypophysectomized rats, as assessed by changes in body weight and the width of the tibial growth plate. These results show that a sustained-release rhGH formulation, DA-3003, has the potential to be used safely and efficaciously in a weekly dosing regimen.

  1. Effects of long-term sustained naltrexone release onthe optic center in opioid-dependent patients Case-control study in four provinces of China

    Institute of Scientific and Technical Information of China (English)

    Shengxi He; Longchuan Yu; Shaowei Jia; Qing Chen; Dongmei Wang; Shu Hu

    2011-01-01

    Very little is known about visual functional recovery following long-term naltrexone administration in opioid-dependent patients. In the present study, a portable event-related potential (ERP) working system was utilized to collect and record ERP in opioid-dependent patients and normal controls in visual half-field testing. In addition, the influence of long-term sustained naltrexone release on the visual nervous system was observed in opioid-dependent patients. Results revealed a significant main group effect in reaction time to visual signal stimulations. The reaction time of normal controls was shortest, but longest in opioid-dependent patients. The reaction time of long-term sustained naltrexone release group and compulsory detoxification group was similar to normal controls. A significant main group effect was also observed in P100 latency, and P100 latency in normal controls and the compulsory detoxification group was significantly decreased compared with the opioid-dependent patients. P100 amplitude at the Oz-electrode resulted in a significant main group effect. In particular, normal controls exhibited significant differences compared with long-term sustained release naltrexone and compulsory detoxification groups. These findings demonstrated that long-term sustained naltrexone release effectively ameliorated optic center function and improved visual sensitivity and reactions in opioid-dependent patients.

  2. 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.

  3. Evaluation of sustained release suppositories prepared with fatty base including solid fats with high melting points.

    Science.gov (United States)

    Takatori, Toshihito; Shimono, Norihito; Higaki, Kazutaka; Kimura, Toshikiro

    2004-07-08

    To prepare the sustained release suppositories, solid fats such as polyglycerol ester of fatty acids (PGEFs) or beeswax were utilized with a fatty suppository base, Witepsol H15. PGEFs such as decaglycerol heptabehenate (HB750) and hexaglycerol pentastearate (PS500), and beeswax have relatively high melting points. The addition of PGEFs or beeswax to Witepsol H15 increased the apparent viscosity of suppository bases at 37 degrees C without any large change in the melting point of Witepsol H15. Moreover, the apparent viscosity of a mixed base with HB750, PS500 or beeswax at 37 degrees C was significantly correlated with the amount of each solid fat in a mixed base. The release of acetaminophen (AAP), a model drug, from suppositories was delayed by HB750, PS500 or beeswax, and an excellent correlation was observed between the apparent viscosity of these mixed bases and Higuchi's rate constants in each mixed base suppository, suggesting that these solid fats could regulate the drug release from the mixed base suppositories by changing their viscosity. In the in vivo absorption study in rats, several suppositories made from Witepsol H15-HB750 or Witepsol H15-beeswax mixed bases prolonged the rectal absorption of AAP without reducing AUC. In conclusion, by using solid fats such as HB750 and beeswax with relatively high melting points, it is possible to control the rate of drug release from fatty base suppositories for maintaining the plasma concentration of drugs for longer time periods.

  4. Effect of polymers on in-vitro performance of eplerenone sustained release matrix tablets

    Directory of Open Access Journals (Sweden)

    Sunil Reddy

    2012-01-01

    Full Text Available Objectives: The intention of the present study was to design and assess oral sustained drug delivery systems for Eplerenone, using Cellulose and natural polymers as release modifiers in the form of matrix tablets. Material and methods: Matrix tablets containing cellulose polymers like HPMC K4M, HPMC K15M, NaCMC and natural polymers like Guar Gum, Xanthan Gum, and Karaya Gum were prepared by wet granulation technique using PVP K60 as a tablet binder. Results: The optimized formulation (F1 contains 1: 0.70 ratio (D: HPMC K4M and (F4 contains 1:1 ratio (D: Guar gum respectively. The in-vitro release kinetic studies of prepared matrix tablets with both the polymers were studied. The kinetic treatment illustrate that the optimized formulation (F1 and F4 followed zero order kinetics with release exponent (n 0.87. Drug content in the tablets and amount of drug released were estimated by reported HPLC method. The FT-IR and DSC studies did not show any interaction of drug with the excipients used in the formulation. Conclusion: The results clearly indicated that Eplerenone could be successfully prepared using an appropriate ratio of cellulose polymers like HPMC K4M, and natural gums like Guar gum in the form of matrix tablets

  5. 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.

  6. A new formulation of Bacillus thuringiensis: UV protection and sustained release mosquito larvae studies

    Science.gov (United States)

    Zhang, Lingling; Zhang, Xiaojuan; Zhang, Yi; Wu, Songqin; Gelbič, Ivan; Xu, Lei; Guan, Xiong

    2016-01-01

    Persistence of Bacillus thuringiensis is an important factor in determining the success of this product as a pest control agent. In this report we present the development of a highly active mosquitocidal formulation with high resistance to UV. LLP29-M19 strain of Bt, selected by repeated exposure to UV was found to be highly resistant to UV. The product was optimized and the methods used were statistically analyzed. Using single-factor experiments it was determined that the optimal concentration of sodium alginate, CaCl2 and hollow glass beads in the formulation were 1.0%, 2.0% and 3.5%, respectively. Plackett-Burman design was used to screen the interaction of the three factors, CaCl2, sodium alginate and hollow glass beads in the sustained-release formulation. The best combined concentration and mutual effects of the three factors were optimized by response surface methodology. The results showed that the most favorable composition was sodium alginate 0.78%, CaCl2 4.52%, hollow glass bead 3.12%, bacterial powder 3.0%, melanin 0.015%, sodium benzoate 0.2%, and mouse feed 0.5%, resulting in the immobilization time of 4.5 h, at which time the corrected sustained-release virulence rose 2391.67 fold, which was 6.07-fold higher than the basic formulation and deviated only 5.0% from the value predicted by RSM. PMID:28004743

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

    Directory of Open Access Journals (Sweden)

    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.

  8. Multifunctional Environmental Smart Fertilizer Based on l-Aspartic Acid for Sustained Nutrient Release.

    Science.gov (United States)

    Lü, Shaoyu; Feng, Chen; Gao, Chunmei; Wang, Xinggang; Xu, Xiubin; Bai, Xiao; Gao, Nannan; Liu, Mingzhu

    2016-06-22

    Fertilizer is one of the most important elements of modern agriculture. However, conventional fertilizer, when applied to crops, is vulnerable to losses through volatilization, leaching, nitrification, or other means. Such a loss limits crop yields and pollutes the environment. In an effort to enhance nutrient use efficiency and reduce environmental pollution, an environmental smart fertilizer was reported in the current study. Poly(aspartic acid) and a degradable macro-cross-linker based on l-aspartic acid were synthesized and introduced into the fertilizer as a superabsorbent to improve the fertilizer degradability and soil moisture-retention capacity. Sustained release behavior of the fertilizer was achieved in soil. Cumulative release of nitrogen and phosphorus was 79.8% and 64.4% after 30 days, respectively. The water-holding and water-retention capacities of soil with the superabsorbent are obviously higher than those of the control soil without superabsorbent. For the sample of 200 g of soil with 1.5 g of superabsorbent, the water-holding capacity is 81.8%, and the water-retention capacity remains 22.6% after 23 days. All of the current results in this study indicated that the as-prepared fertilizer has a promising application in sustainable modern agriculture.

  9. 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.

  10. Lack of endogenous opioid release during sustained visceral pain: a [11C]carfentanil PET study.

    Science.gov (United States)

    Ly, Huynh Giao; Dupont, Patrick; Geeraerts, Brecht; Bormans, Guy; Van Laere, Koen; Tack, Jan; Van Oudenhove, Lukas

    2013-10-01

    Opioidergic neurotransmission in the central nervous system is involved in somatic pain, but its role in visceral pain remains unknown. We aimed to quantify endogenous opioid release in the brain during sustained painful gastric distension. Therefore, 2 dynamic [11C]carfentanil positron emission tomography scans were performed in 20 healthy subjects during 2 conditions: sustained (20 minutes) painful proximal gastric balloon distension at predetermined individual discomfort threshold (PAIN) and no distension (NO PAIN), in counterbalanced order. Pain levels were assessed during scanning using visual analogue scales and after scanning using the McGill Pain Questionnaire. Emotional state was rated after scanning using the Positive and Negative Affect Schedule. Distribution volume ratios in 21 volumes of interest in the pain matrix were used to quantify endogenous opioid release. During the PAIN compared to the NO PAIN condition, volunteers reported a significantly higher increase in negative affect (5.50±1.29 versus 0.10±1.08, P=.0147) as well as higher pain ratings (sensory: 74.05±9.23 versus 1.50±0.95, Pvisceral pain, despite similar pain intensities. Endogenous opioids may play a less important role in visceral compared to somatic pain. Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  11. Sustained PDGF-BB release from PHBHHx loaded nanoparticles in 3D hydrogel/stem cell model.

    Science.gov (United States)

    Dong, Cui-Ling; Webb, William R; Peng, Qiang; Tang, James Z; Forsyth, Nicholas R; Chen, Guo-Qiang; El Haj, Alicia J

    2015-01-01

    This study aimed to design a growth factor loaded copolyester of 3-hydroxybutyrate and 3-hydroxyhexanoate (PHBHHx) nanoparticles containing 3D collagen matrix to achieve growth factor sustained release for long-term stimulation of human mesenchymal stem cells (hMSCs) proliferation/differentiation for tissue engineer application. Platelet-derived growth factor-BB (PDGF-BB), which is known to enhance hMSCs proliferation in human serum, was selected as a model growth factor, and biodegradable copolyester of PHBHHx was chosen to be the sustained release vehicle. PDGF-BB phospholipid complex encapsulated PHBHHx nanoparticles were fabricated, and their effect on hMSCs proliferation was investigated via assays of CCK-8 and live-dead staining to cells inoculated in 2D tissue culture plates and 3D collagen gel scaffolds, respectively. The resulting spherical PHBHHx nanoparticles were stable in terms of their mean particle size, polydispersity index and zeta potential before and after lyophilization. In vitro study revealed a sustained release of PDGF-BB with a low burst release. Furthermore, sustained released PDGF-BB was revealed to significantly promote hMSCs proliferation in both cell monolayer and cell seeded 3D collagen scaffolds inoculated in serum-free media. Therefore, the 3D collagen matrices with locally sustained release growth factor nanoparticles hold promise to be used for stem cell tissue engineering.

  12. 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

    To improve the bioavailability of nitrendipine microspheres, a sustained-release microspheres having solid dispersion structure were prepared in one step. Two types of polymer, i.e. solid dispersing and sustained-release polymers, were employed to prepare the microspheres by the spherical...... crystallization technique, i.e. quasi-emulsion solvent diffusion method. The factors of effect on micromeritic properties and release profiles of the resultant microspheres were investigated. And the bioavailability of nitrendipine microspheres was evaluated in six healthy dogs. The results showed...... 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...

  13. 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.

  14. 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

    2017-02-15

    There was a paradox to incorporate enzyme into edible chitosan film that chitosan was dissolved in acid solution and enzyme activity was maintained in mild condition. This study presents a suitable method for maintaining the pH of the chitosan solution at 4-6 to prepare a sustained-release film containing β-cyclodextrin, resveratrol-β-cyclodextrin inclusion (RCI), 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 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 EDS presented the following order: GAF, GFFW, GFF and GAFW.

  15. 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

  16. OTO-201: nonclinical assessment of a sustained-release ciprofloxacin hydrogel for the treatment of otitis media.

    Science.gov (United States)

    Wang, Xiaobo; Fernandez, Rayne; Tsivkovskaia, Natalia; Harrop-Jones, Anne; Hou, Huiying J; Dellamary, Luis; Dolan, David F; Altschuler, Richard A; LeBel, Carl; Piu, Fabrice

    2014-03-01

    OTO-201 can provide sustained release to the middle ear and effectively treat otitis media, when compared with FDA-approved ciprofloxacin otic drop formulations. There is an unmet medical need for antibiotic therapy that can provide a full course of treatment from a single administration by an otolaryngologist at the time of tympanostomy tube placement, obviating the need for twice daily multiday treatment with short-acting otic drops. Studies in guinea pigs and chinchillas were conducted. OTO-201 was administered as a single intratympanic injection and compared with the twice daily multi-day treatment with Ciprodex or Cetraxal otic drops. OTO-201 demonstrated sustained release of ciprofloxacin in the middle ear compartment for days to approximately 2 weeks depending on the dose. The substantial C(max) values and steady drug exposure yielded by OTO-201 were in contrast to the pulsatile short lasting exposure seen with Ciprodex and Cetraxal. OTO-201 was also effective in a preclinical chinchilla model of Streptococcus pneumoniae-induced otitis media. The degree of cure was comparable to that afforded by Ciprodex and Cetraxal. There was no evidence of middle or inner ear pathology in guinea pigs treated with OTO-201, unlike Ciprodex and Cetraxal, which both demonstrated mild cochlear ototoxicity. No adverse effects of the poloxamer 407 vehicle were noted. Intratympanic injection of OTO-201 constitutes an attractive treatment option to twice daily multiday dosing with ciprofloxacin ear drops for the treatment of otitis media, as evidenced by superior middle ear drug exposure, efficacy in an acute otitis media model, safety of administration, and convenience of a single dose regimen.

  17. Design and evaluation of guar gum-based ofloxacin sustained release ocular insert

    Directory of Open Access Journals (Sweden)

    Sunil Kumar

    2012-01-01

    Full Text Available To prepare ocular inserts of ofloxacin using guar gum as a polymer for sustained delivery over a period of 24 h. Ofloxacin ocular inserts were prepared by the solvent casting method using guar gum in different proportions (0.5% w/v, 0.75% w/v and 1.0% w/v. The prepared formulations were evaluated for thickness, weight variation, percentage drug content, surface pH, folding endurance, percentage moisture absorption and loss, percentage swelling, mechanical strength and in vitro transcorneal permeation. In vitro transcorneal permeation study was performed on goat cornea using a modified Franz diffusion cell. The inserts were found to be of uniform thickness (ranging from 51.230 ± 0.385 μm to 109.275 ± 0.522 μm and weight (1.720 ± 0.079 mg to 3.402 ± 0.105 mg. The % drug content in the inserts was found to vary between 95.450 ± 0.427% and 98.471 ± 0.225. The cumulative % drug releases from the formulation ranged from 38.19 to 75.21 over a period of 24 h. All the formulations followed a zero order release pattern. The in vitro transcorneal study revealed that an increase in concentration of the polymer slowed down the release of ofloxacin from the formulation. Ocular inserts using guar gum as a polymer were successfully prepared and can be effectively used for sustained ocular delivery over a period of 24 h.

  18. The in vitro sustained release profile and antitumor effect of etoposide-layered double hydroxide nanohybrids

    Directory of Open Access Journals (Sweden)

    Qin LL

    2013-05-01

    Full Text Available Lili Qin,1 Mei Wang,2 Rongrong Zhu,3 Songhui You,1 Ping Zhou,1 Shilong Wang31Department of Physical Education, Tongji University, Shanghai, People's Republic of China; 2Department of Chemistry, Tongji University, Shanghai, People's Republic of China; 3School of Life Science and Technology, Tongji University, Shanghai, People's Republic of ChinaAbstract: Magnesium-aluminum layered double hydroxides intercalated with antitumor drug etoposide (VP16 were prepared for the first time using a two-step procedure. The X-ray powder diffraction data suggested the intercalation of VP16 into layers with the increased basal spacing from 0.84–1.18 nm was successful. Then, it was characterized by X-ray powder diffraction, Fourier transform infrared spectroscopy, thermogravimetry and differential thermal analysis, and transmission electron microscopy. The prepared nanoparticles, VP16-LDH, showed an average diameter of 62.5 nm with a zeta potential of 20.5 mV. Evaluation of the buffering effect of VP16-LDH indicated that the nanohybrids were ideal for administration of the drugs that treat human stomach irritation. The loading amount of intercalated VP16 was 21.94% and possessed a profile of sustained release. The mechanism of VP16-LDH release in the phosphate buffered saline solution at pH 7.4 is likely controlled by the diffusion of VP16 anions from inside to the surface of LDH particles. The in vitro cytotoxicity and antitumor assays indicated that VP16-LDH hybrids were less toxic to GES-1 cells while exhibiting better antitumor efficacy on MKN45 and SGC-7901 cells. These results imply that VP16-LDH is a potential antitumor drug for a broad range of gastric cancer therapeutic applications.Keywords: layered double hydroxides, etoposide, drug delivery, antitumor effect, sustained release

  19. Development and evaluation of sustained-release ibuprofen-wax microspheres. II. In vitro dissolution studies.

    Science.gov (United States)

    Adeyeye, C M; Price, J C

    1994-04-01

    A modified USP paddle method using minibaskets was used to study the effects of various formulations on in vitro dissolution of ibuprofen microspheres. Formulations containing waxes such as paraffin or ceresine wax without modifiers exhibited very slow dissolution profiles and incomplete release, which did not improve with increased drug loading or the preparation of smaller microspheres. The addition of modifiers such as stearyl alcohol and glyceryl monostearate greatly increased the dissolution rate, with 20% (w/w) near the optimum for predictable dissolution. Higher drug loading and decreased microsphere size increased the dissolution rate from microspheres containing modifier. Optimum formulations contained ceresine wax or microcrystalline wax and stearyl alcohol as a modifier, with a drug content of 17%. An increase in the encapsulation dispersant concentration had little effect on the dissolution profiles. The dissolution data from narrow size fractions of microspheres indicated spherical matrix drug release kinetics; the 50% dissolution time decreased with the square of the microsphere diameter. With appropriate modifiers, wax microsphere formulations of drugs with solubility characteristics similar to those of ibuprofen can offer a starting basis for predictable sustained release dosage forms.

  20. Thermo-Responsive Injectable MPEG-Polyester Diblock Copolymers for Sustained Drug Release

    Directory of Open Access Journals (Sweden)

    Hoon Hyun

    2014-10-01

    Full Text Available Thermo-responsive diblock copolymers composed of hydrophilic methoxy poly(ethylene glycol (MPEG and hydrophobic biodegradable polyesters were prepared for application as injectable drug delivery systems, because they show a thermo-responsive sol-to-gel transition, especially around body temperature, when dispersed in aqueous solutions. The thermogelling hydrogels formed by hydrophobic aggregation could be varied by changing the components of the hydrophobic polyester part. For the polyester block in the present study, 95 mol% of ε-caprolactone (CL was used for the main polyester chain and 5 mol% of p-dioxanone (DO was copolymerized randomly by the MPEG initiator in the presence of HCl as the catalyst. By adding a small portion of DO into the poly ε-caprolactone (PCL chains, the temperature range of gelation, the intensity of viscosity and the drug release behavior were changed. The MPEG-b-poly(ε-caprolactone-ran-p-dioxanone (MPEG-b-PCDO hydrogel showed the enhanced drug release in vitro and in vivo compared to MPEG-b-PCL hydrogel. Therefore, MPEG-polyester hydrogels may serve as minimally invasive and therapeutic, injectable hydrogel systems with adjustable temperature-responsive and biodegradable windows, as well as sustained release of drugs over a certain time period.

  1. Locust bean gum in the development of sustained release mucoadhesive macromolecules of aceclofenac.

    Science.gov (United States)

    Prajapati, Vipul D; Jani, Girish K; Moradiya, Naresh G; Randeria, Narayan P; Maheriya, Pankaj M; Nagar, Bhanu J

    2014-11-26

    The study shows the development and optimization of locust bean gum (LBG)-alginate mucoadhesive macromolecules containing aceclofenac through ionotropic-gelation using 3(2) factorial design. The effect of amount of LBG and sodium alginate on drug entrapment efficiency (%DEE), % mucoadhesion at 8h (M8) and % in vitro drug release at 10h (%Q10h) were optimized. The percentage yield, average size and DEE of macromolecules were found within the range of 93.19 to 96.65%, 1.328 ± 0.11 to 1.428 ± 0.13 μm, and 56.37 to 68.54%, respectively. The macromolecules were also characterized by SEM, FTIR and DSC. The in vitro drug release from these macromolecules (84.95 ± 2.02 to 95.33 ± 1.56% at 10h) exhibited sustained release (first-order) pattern with super case-II transport mechanism. The swelling and mucoadhesivity of these macromolecules were affected by pH of the medium. The design established the role of derived polynomial equations and plots in predicting the values of dependent variables for the preparation and optimization. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Strong cation exchange resin for improving physicochemical properties and sustaining release of ranitidine hydrochloride

    Directory of Open Access Journals (Sweden)

    Khan S

    2007-01-01

    Full Text Available In the present study strong cation exchange resin (Amberlite IRP69 was used to improve the physicochemical properties of ranitidine hydrochloride such as taste and bulk properties and to sustain dissolution rate. Drug-resin complexes were prepared using batch method. Drug loading was done under different processing conditions such as temperature, pH, drug-resin ratio, and drug concentration to get the optimum condition for resinate preparation. Resinate prepared under optimized condition was tested for taste, bulk properties and release rate. Degree of bitterness of ranitidine was found to reduce to zero after complexation with resin. Improvement in flow properties was also observed. Angle of repose for resinate was found to be 33.21 o as compared to 42.27 o for ranitidine HCl. Effect of dissolution medium and particle size on in vitro release of drug from resinate was also investigated. Resinate with drug to resin ratio of 2:3 and particle size> 90 µm showed about 90% of drug release within 12 h. The orodispersible tablet formulated from the resinate containing 10% croscarmellose sodium disintegrated within 35 sec in oral cavity and showed similar dissolution profile as the resinate. Tablets were found stable after stability studies with no change in dissolution profile.

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

    Directory of Open Access Journals (Sweden)

    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.

  4. 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.

  5. 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.

  6. 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.

  7. Influence of formulation and process parameters on the release characteristics of ethylcellulose sustained-release mini-matrices produced by hot-melt extrusion.

    Science.gov (United States)

    Verhoeven, E; De Beer, T R M; Van den Mooter, G; Remon, J P; Vervaet, C

    2008-05-01

    Mini-matrices (multiple unit dosage form) with release-sustaining properties were developed by hot-melt extrusion (cylindrical die: 3mm) using metoprolol tartrate as model drug and ethylcellulose as sustained-release agent. Dibutyl sebacate was selected as plasticizer and its concentration was optimized to 50% (w/w) of the ethylcellulose concentration. Xanthan gum, a hydrophilic polymer, was added to the formulation to increase drug release. Changing the xanthan gum concentration modified the in vitro drug release: increasing xanthan gum concentrations (1%, 2.5%, 5%, 10% and 20%, w/w) yielded a faster drug release. Zero-order drug release was obtained at 5% (w/w) xanthan gum. Using kneading paddles, smooth extrudates were obtained when processed at 60 degrees C. At least one mixing zone was required to obtain smooth and homogeneous extrudates. The mixing efficacy and drug release were not affected by the number of mixing zones or their position along the extruder barrel. Raman analysis revealed that metoprolol tartrate was homogeneously distributed in the mini-matrices, independent of screw design and processing conditions. Simultaneously changing the powder feed rate (6-25-50 g/min) and screw speed (30-100-200 rpm) did not alter extrudate quality or dissolution properties.

  8. Nanosized sustained-release drug depots fabricated using modified tri-axial electrospinning.

    Science.gov (United States)

    Yang, Guang-Zhi; Li, Jiao-Jiao; Yu, Deng-Guang; He, Mei-Feng; Yang, Jun-He; Williams, Gareth R

    2017-01-27

    Nanoscale drug depots, comprising a drug reservoir surrounded by a carrier membrane, are much sought after in contemporary pharmaceutical research. Using cellulose acetate (CA) as a filament-forming polymeric matrix and ferulic acid (FA) as a model drug, nanoscale drug depots in the form of core-shell fibers were designed and fabricated using a modified tri-axial electrospinning process. This employed a solvent mixture as the outer working fluid, as a result of which a robust and continuous preparation process could be achieved. The fiber-based depots had a linear morphology, smooth surfaces, and an average diameter of 0.62±0.07μm. Electron microscopy data showed them to have clear core-shell structures, with the FA encapsulated inside a CA shell. X-ray diffraction and IR spectroscopy results verified that FA was present in the crystalline physical form. In vitro dissolution tests revealed that the fibers were able to provide close to zero-order release over 36h, with no initial burst release and minimal tailing-off. The release properties of the depot systems were much improved over monolithic CA/FA fibers, which exhibited a significant burst release and also considerable tailing-off at the end of the release experiment. Here we thus demonstrate the concept of using modified tri-axial electrospinning to design and develop new types of heterogeneous nanoscale biomaterials.

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

    Directory of Open Access Journals (Sweden)

    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.

  10. Preparation and evaluation of sustained-release solid dispersions co-loading gastrodin with borneol as an oral brain-targeting enhancer

    Directory of Open Access Journals (Sweden)

    Zheng Cai

    2014-02-01

    Full Text Available Borneol is a traditional Chinese medicine that can promote drug absorption from the gastrointestinal tract and distribution to the brain. However, stomach irritation may occur when high doses of borneol are used. In the present work, gastrodin, the main bioactive ingredient of the traditional Chinese drug “Tianma” (Rhizoma Gastrodiae was used as a model drug to explore reasonable application of borneol. Sustained-release solid dispersions (SRSDs for co-loading gastrodin and borneol were prepared using ethylcellulose as a sustained release matrix and hydroxy-propyl methylcellulose as a retarder. The dispersion state of drug within the SRSDs was analyzed by using scanning electron microscopy, differential scanning calorimetry, and powder X-ray diffractometry. The results indicated that both gastrodin and borneol were molecularly dispersed in an amorphous form. Assay of in vitro drug release demonstrated that the dissolution profiles of gastrodin and borneol from the SRSDs both fitted the Higuchi model. Subsequently, gastric mucosa irritation and the brain targeting of the SRSDs were evaluated. Compared with the free mixture of gastrodin and borneol, brain targeting of SRSDs was slightly weaker (brain targeting index: 1.83 vs. 2.09, but stomach irritation obviously reduced. Sustained-release technology can be used to reduce stomach irritation caused by borneol while preserving sufficient transport capacity for oral brain-targeting drug delivery.

  11. Dual ionic interaction system based on polyelectrolyte complex and ionic, injectable, and thermosensitive hydrogel for sustained release of human growth hormone.

    Science.gov (United States)

    Park, Mi-Ran; Seo, Bo-Bae; Song, Soo-Chang

    2013-01-01

    A dual ionic interaction system composed of a positively charged polyelectrolyte complex (PEC) containing human growth hormone (hGH) and anionic thermosensitive hydrogel has been suggested for sustained delivery of bioactive hGH. The PEC was prepared by ionic interaction between negatively charged hGH and positively charged protamine sulfate (PS) to suppress diffusion of hGH. Moreover, we loaded the positively charged PEC into an anionic, injectable, and thermosensitive poly(organophosphazene) hydrogel to enhance sustained release of hGH by dual ionic interactions. PS formed a spherical complex with hGH, and their ionic interaction grew stronger with increasing amounts of PS. From a weight ratio of 0.5, the PS/hGH complex had a size and zeta-potential that were constantly maintained around 500 nm and +8 mV, respectively, in 0.9% NaCl. The PEC-loaded hydrogels suppressed the initial burst release of hGH and extended the release period in vitro and in vivo. In a pharmacokinetic study in rats, the PEC-loaded anionic hydrogel extended half-life 13-fold with similar area under the curve (AUC) compared to hGH solution. Furthermore, single injection of PEC-loaded anionic hydrogel showed a more increased growth rate than daily injection of hGH solution for 7 days in hypophysectomized rats, demonstrating its potential as an injectable, sustained delivery system that can release bioactive hGH.

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

    Directory of Open Access Journals (Sweden)

    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.

  13. Sustained release of tissue factor following thrombosis of lower limb trauma.

    Science.gov (United States)

    Walenga, Jeanine M; Kaiser, Phoebe C; Prechel, M Margaret; Hoppensteadt, Debra; Jeske, Walter P; Misselwitz, Frank; Bacher, Peter; Lassen, Michael R; Fareed, Jawed

    2014-10-01

    This study was undertaken to provide evidence for the mechanism of venous thromboembolism (VTE) in healthy patients with minor lower limb injury (fracture; Achilles tendon rupture) that was medically managed with plaster cast/brace immobilization. The Plaster Cast clinical trial provided a unique opportunity to identify the natural history of VTE using placebo-controlled patients (n = 183) with validation of the mechanism using the low-molecular-weight heparin (LMWH; reviparin)-treated patients (n = 182). Confirmed VTE in this population was associated with a burst of tissue factor release (and a minor fibrinolytic deficit) leading to thrombin generation that was sustained at least 5 weeks, greater with fractures than with soft-tissue injuries and greater with surgery than with conservative treatment. The root cause likely involves platelet/leukocyte activation (inflammation) rather than endothelial cell injury. Thromboprophylaxis with a low dose of LMWH reduced thrombin generation, with patients undergoing surgery benefitting the most.

  14. Treatment of cytomegalovirus retinitis with an intraocular sustained-release ganciclovir implant

    Directory of Open Access Journals (Sweden)

    Muccioli C.

    2000-01-01

    Full Text Available The objective of this prospective study was to evaluate the efficacy and complications of the use of an intraocular sustained-release ganciclovir implant for the treatment of active cytomegalovirus (CMV retinitis in AIDS patients. Thirty-nine eyes of 26 patients were submitted to ocular surgery. All patients underwent complete ocular examination before and after surgery. The surgical procedure was always done under local anesthesia using the same technique. The mean time for the surgical procedure was 20 min (range, 15 to 30 min. The average follow-up period was 3.7 months. Of all patient, only 4 presented recurrence of retinitis after 8, 8, 9 and 2 months, respectively. Three of them received a successful second implant. All 39 eyes of the 26 patients presented healing of retinitis as shown by clinical improvement evaluated by indirect binocular ophthalmoscopy and retinography. Retinitis healed within a period of 4 to 6 weeks in all patients, with clinical regression signs from the third week on. Six (15.4% eyes developed retinal detachment. None of the patients developed CMV retinitis in the contralateral eye. The intraocular implant proved to be effective in controlling the progression of retinitis for a period of up to 8 months even in patients for whom systemic therapy with either ganciclovir or foscarnet or both had failed. The intraocular sustained-release ganciclovir implant proved to be a safe new procedure for the treatment of CMV retinitis, avoiding the systemic side effects caused by the intravenous medications and improving the quality of life of the patients.

  15. Buprenorphine for pain relief in mice: repeated injections vs sustained-release depot formulation.

    Science.gov (United States)

    Jirkof, P; Tourvieille, A; Cinelli, P; Arras, M

    2015-07-01

    Sustained-release formulations of analgesic drugs are promising alternatives to repeated drug injections. Here, we compared a sustained-release formulation of buprenorphine (SB, 2.2 mg/kg) with a standard protocol of three injections of buprenorphine (Temgesic, 0.1 mg/kg/8 h) in mice. Buprenorphine serum concentration and analgesic action (thermal sensitivity) were determined in healthy mice. Additionally, the pain relief properties of both protocols were assessed after laparotomy using physiological and ethological measures of pain and recovery. Serum concentrations and thermal sensitivity tests indicated duration of action of at least 4 h (but less than 8 h) with the Temgesic protocol, and 24-48 h with SB. Behavioural and clinical parameters indicated at least partial pain relief after surgery for both protocols. Observed side-effects of buprenorphine independent of the protocol were increased activity, disturbed circadian rhythm and several abnormal behaviours. A tendency for decreased food and water intake as well as body weight reduction was also seen. Body weight decreased significantly in animals that received three injections of Temgesic, regardless of whether surgery was performed or not (P = 0.015; P = 0.023), hinting at a stress response towards this repeated intervention. In conclusion, an application interval of 8 h (Temgesic) appears too long and might lead to repeated periods with insufficient analgesia in animals undergoing lasting and/or substantial pain after surgery. In comparison to the standard protocol, SB provided a long-lasting, assured analgesia without possible stressful repeated injections in a standard surgical model, with only limited and acceptable behavioural side-effects.

  16. Formulation and In Vitro Characterization of Xanthan Gum-Based Sustained Release Matrix Tables of Isosorbide-5- Mononitrate

    Science.gov (United States)

    Kar, Rajat; Mohapatra, Snehamayee; Bhanja, Satyabrata; Das, Debjyoti; Barik, Bhaktibhusan

    2010-01-01

    In the present investigation an attempt has been made to increase therapeutic efficacy, to reduce frequency of administration and to improve patient compliance by developing a sustained release matrix tablets of isosorbide-5-mononitrate. Sustained release matrix tablets of isosorbide-5-mononitrate were developed by using different drug: polymer ratios, such in F1 (1:0.75), F2 (1:1), F3 (1:1.5), F4 (1:1.75) and F6 (1:2). Xanthan gum was used as matrix former and microcrystalline cellulose as diluent. All the lubricated formulations were compressed, using 8mm flat faced punches. Compressed tablets were evaluated for uniformity of weight, content of active ingredient, friability, hardness, thickness, in vitro dissolution study using basket method and swelling index. Each formulation showed compliance with pharmacopoeial standards. Among all formulations, F5 showed a greater sustained release pattern of drug over a 12 h period with 92.12% of drug being released. The kinetic studies showed that drug release follows the Higuchi model (r2 =0.9851). Korsemeyer and Peppas equation gave an n-value of 0.4566, which was close to 0.5, indicating that drug release follows the Fickian diffusion. Thus, xanthan gum can be used as an effective matrix former to extend the release of isosorbide-5-mononitrate. No significant difference was observed in the dissolution profile of optimized formulation, using basket and paddle apparatus. PMID:24363701

  17. Silk fibroin/copolymer composite hydrogels for the controlled and sustained release of hydrophobic/hydrophilic drugs.

    Science.gov (United States)

    Zhong, Tianyi; Jiang, Zhijuan; Wang, Peng; Bie, Shiyu; Zhang, Feng; Zuo, Baoqi

    2015-10-15

    In the present study, a composite system for the controlled and sustained release of hydrophobic/hydrophilic drugs is described. Composite hydrogels were prepared by blending silk fibroin (SF) with PLA-PEG-PLA copolymer under mild aqueous condition. Aspirin and indomethacin were incorporated into SF/Copolymer hydrogels as two model drugs with different water-solubility. The degradation of composite hydrogels during the drug release was mainly caused by the hydrolysis of copolymers. SF with stable β-sheet-rich structure was not easily degraded which maintained the mechanical integrity of composite hydrogel. The hydrophobic/hydrophilic interactions of copolymers with model drugs would significantly alter the morphological features of composite hydrogels. Various parameters such as drug load, concentration ratio, and composition of copolymer were considered in vitro drug release. Aspirin as a hydrophilic drug could be controlled release from composite hydrogel at a constant rate for 5 days. Its release was mainly driven by diffusion-based mechanism. Hydrophobic indomethacin could be encapsulated in copolymer nanoparticles distributing in the composite hydrogel. Its sustained release was mainly degradation controlled which could last up to two weeks. SF/Copolymer hydrogel has potential as a useful composite system widely applying for controlled and sustained release of various drugs.

  18. Specification aggregate quarry expansion: a case study demonstrating sustainable management of natural aggregate resources

    Science.gov (United States)

    Langer, William H.; Tucker, M.L.

    2003-01-01

    Many countries, provinces, territories, or states in the European Union, Australia, Canada, the United States, and elsewhere have begun implementing sustainability programs, but most of those programs stop short of sustainable management of aggregate resources. Sustainable practices do not always have to be conducted under the title of sustainability. This case study describes how Lafarge, a large multinational construction materials supplier, implemented the principles of sustainability even though there was an absence of existing local government policies or procedures addressing sustainable resource management. Jefferson County, Colorado, USA, is one of three counties in the six-county Denver, Colorado, region that has potentially available sources of crushed stone. Crushed stone comprises 30 percent of the aggregate produced in the area and plays a major role in regional aggregate resource needs. Jefferson County is home to four of the five crushed stone operations in the Denver region. Lafarge operates one of those four quarries. Lafarge recently proposed to expand its reserves by exchanging company-owned land for existing dedicated open space land adjacent to their quarry but owned by Jefferson County. A similar proposal submitted about 10 years earlier had been denied. Contrary to the earlier proposal, which was predicated on public relations, the new proposal was predicated on public trust. Although not explicitly managed under the moniker of sustainability, Lafarge used basic management principles that embody the tenets of sustainability. To achieve the goals of sustainable aggregate management where no governmental policies existed, Lafarge not only assumed their role of being a responsible corporate and environmental member of the community, but also assumed the role of facilitator to encourage and enable other stakeholders to responsibly resolve legitimate concerns regarding the Lafarge quarry proposal. Lafarge successfully presented an enlightened

  19. Thermoresponsive magnetic nanoparticle--aminated guar gum hydrogel system for sustained release of doxorubicin hydrochloride.

    Science.gov (United States)

    Murali, Ragothaman; Vidhya, Ponraj; Thanikaivelan, Palanisamy

    2014-09-22

    Hydrogel based sustained drug delivery system has evolved as an immense treatment method for solid tumors over the past few decades with long term theranostic ability. Here, we synthesized an injectable hydrogel system comprising biocompatible aminated guar gum, Fe3O4-ZnS core-shell nanoparticles and doxorubicin hydrochloride. We show that amination of guar gum resulted in attraction of water molecules thereby forming the hydrogel without using toxic crosslinking agents. Hydrogel formation was observed at 37°C and is stable up to 95°C. The prepared hydrogel is also stable over a wide pH range. The in vitro studies show that the maximum de-gelation and drug release up to 90% can be achieved after 20 days of incubation. Studies reveal that the drug and the core-shell nanoparticles can be released slowly from the hydrogel to provide the healing and diagnosis of the solid tumor thereby avoiding several drug administrations and total excision of organs.

  20. A genetically engineered thermally responsive sustained release curcumin depot to treat neuroinflammation.

    Science.gov (United States)

    Sinclair, S Michael; Bhattacharyya, Jayanta; McDaniel, Jonathan R; Gooden, David M; Gopalaswamy, Ramesh; Chilkoti, Ashutosh; Setton, Lori A

    2013-10-10

    Radiculopathy, a painful neuroinflammation that can accompany intervertebral disc herniation, is associated with locally increased levels of the pro-inflammatory cytokine tumor necrosis factor alpha (TNFα). Systemic administration of TNF antagonists for radiculopathy in the clinic has shown mixed results, and there is growing interest in the local delivery of anti-inflammatory drugs to treat this pathology as well as similar inflammatory events of peripheral nerve injury. Curcumin, a known antagonist of TNFα in multiple cell types and tissues, was chemically modified and conjugated to a thermally responsive elastin-like polypeptide (ELP) to create an injectable depot for sustained, local delivery of curcumin to treat neuroinflammation. ELPs are biopolymers capable of thermally-triggered in situ depot formation that have been successfully employed as drug carriers and biomaterials in several applications. ELP-curcumin conjugates were shown to display high drug loading, rapidly release curcumin in vitro via degradable carbamate bonds, and retain in vitro bioactivity against TNFα-induced cytotoxicity and monocyte activation with IC50 only two-fold higher than curcumin. When injected proximal to the sciatic nerve in mice via intramuscular (i.m.) injection, ELP-curcumin conjugates underwent a thermally triggered soluble-insoluble phase transition, leading to in situ formation of a depot that released curcumin over 4days post-injection and decreased plasma AUC 7-fold. © 2013.

  1. A Genetically Engineered Thermally Responsive Sustained Release Curcumin Depot to Treat Neuroinflammation

    Science.gov (United States)

    Sinclair, S. Michael; Bhattacharyya, Jayanta; McDaniel, Jonathan R.; Gooden, David M.; Gopalaswamy, Ramesh; Chilkoti, Ashutosh; Setton, Lori A.

    2014-01-01

    Radiculopathy, a painful neuroinflammation that can accompany intervertebral disc herniation, is associated with locally increased levels of the pro-inflammatory cytokine tumor necrosis factor alpha (TNFα). Systemic administration of TNF antagonists for radiculopathy in the clinic has shown mixed results, and there is growing interest in the local delivery of anti-inflammatory drugs to treat this pathology as well as similar inflammatory events of peripheral nerve injury. Curcumin, a known antagonist of TNFα in multiple cell types and tissues, was chemically modified and conjugated to a thermally responsive elastin-like polypeptide (ELP) to create an injectable depot for sustained, local delivery of curcumin to treat neuroinflammation. ELPs are biopolymers capable of thermally-triggered in situ depot formation that have been successfully employed as drug carriers and biomaterials in several applications. ELP-curcumin conjugates were shown to display high drug loading, rapidly release curcumin in vitro via degradable carbamate bonds, and retain in vitro bioactivity against TNFα-induced cytotoxicity and monocyte activation with IC50 only two-fold higher than curcumin. When injected proximal to the sciatic nerve in mice via intramuscular (i.m.) injection, ELP-curcumin conjugates underwent a thermally triggered soluble-insoluble phase transition, leading to in situ formation of a depot that released curcumin over 4 days post-injection and decreased plasma AUC 7-fold. PMID:23830979

  2. 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%.

  3. 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.

  4. 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

  5. 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

  6. A novel sustained release drug-resin complex-based microbeads of ciprofloxacin HCl.

    Science.gov (United States)

    Jain, Sunil K; Prajapati, Neeraj; Rajpoot, Kuldeep; Kumar, Amrish

    2016-12-01

    Objective A novel multiparticulate system for the gastro-mucoadhesive delivery of ciprofloxacin HCl (CFN) was developed with the help of ion-exchange resin to deal with urinary tract (UT) infections effectively. Materials and methods An optimized complex (resinate) of CFN with sodium polystyrene sulfonate USP resin was prepared and entrapped within microbeads of sodium alginate and pectin. The developed systems were evaluated for drug entrapment efficiency, percentage of mucoadhesion and in vitro release patterns in simulated gastric fluid (pH 1.2). Results and discussion The interaction of the resin complex and polycation via alginate was consequently supported the formation of polyelectrolyte complex membrane. The in vitro drug release studies demonstrate that formulation without drug-resin complex (NRB) released the drug more swiftly than formulation containing drug-resin complex (DRC). This controlled release pattern of drug, resin complex containing microbeads was owed to complexation between drug and resin. Conclusion Preliminary results from the study suggested that this drug-resin complex-entrapped microbeads can be used to incorporate other antibiotic drugs and could be effective against UT infection. Such developed formulation could be subjected to in vivo studies in future in order to prove their efficacy for such type of infections.

  7. ION EXCHANGE RESINS: AN APPROACH TOWARDS TASTE MASKING OF BITTER DRUGS AND SUSTAINED RELEASE FORMULATIONS WITH THEIR PATENTS

    Directory of Open Access Journals (Sweden)

    Ajay Bilandi

    2013-08-01

    Full Text Available The purpose of this review is to cover various aspects related with the use of ion exchange resins for taste masking of bitter drugs and for formulating sustained release dosage form. Ion exchange resins are water insoluble cross-linked polymers containing a salt-forming group at repeating positions on the polymer chain and have the ability to exchange counter-ions within aqueous solutions surrounding them. The bitterness of pharmaceutical medicines plays a critical role in patient compliance, as the oral administration of bitter drugs is often hampered by their unpleasant taste which leads to non-compliance and further worsening of diseased condition. One of the popular approaches in the taste masking of bitter drugs is based on IER. For taste masking purpose weak cation exchange or weak anion exchange resins are used, depending on the nature of drug. The drug resin complex is absolutely tasteless with no after taste, and at the same time, its bioavailability is not affected. Sustained release dosage forms are designed to release a drug at a pre determined rate in order to maintain a constant drug concentration for a specific period of time with minimum side effects. The usage of IER during the development of sustained release formulations plays a significant role because of their drug retarding properties. In this review also incorporates various patents related to taste masking and sustained release formulations using IER.

  8. 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

  9. Application of terahertz pulsed imaging to analyse film coating characteristics of sustained-release coated pellets.

    Science.gov (United States)

    Haaser, M; Karrout, Y; Velghe, C; Cuppok, Y; Gordon, K C; Pepper, M; Siepmann, J; Rades, T; Taday, P F; Strachan, C J

    2013-12-05

    Terahertz pulsed imaging (TPI) was employed to explore its suitability for detecting differences in the film coating thickness and drug layer uniformity of multilayered, sustained-release coated, standard size pellets (approximately 1mm in diameter). Pellets consisting of a sugar starter core and a metoprolol succinate layer were coated with a Kollicoat(®) SR:Kollicoat(®) IR polymer blend for different times giving three groups of pellets (batches I, II and III), each with a different coating thickness according to weight gain. Ten pellets from each batch were mapped individually to evaluate the coating thickness and drug layer thickness between batches, between pellets within each batch, and across individual pellets (uniformity). From the terahertz waveform the terahertz electric field peak strength (TEFPS) was used to define a circular area (approximately 0.13 mm(2)) in the TPI maps, where no signal distortion was found due to pellet curvature in the measurement set-up used. The average coating thicknesses were 46 μm, 71 μm and 114 μm, for batches I, II and III respectively, whilst no drug layer thickness difference between batches was observed. No statistically significant differences in the average coating thickness and drug layer thickness within batches (between pellets) but high thickness variability across individual pellets was observed. These results were confirmed by scanning electron microscopy (SEM). The coating thickness results correlated with the subsequent drug release behaviour. The fastest drug release was obtained from batch I with the lowest coating thickness and the slowest from batch III with the highest coating thickness. In conclusion, TPI is suitable for detailed, non-destructive evaluation of film coating and drug layer thicknesses in multilayered standard size pellets.

  10. Sustained Release of Mitomycin C from Its Conjugate with Single-Walled Carbon Nanotubes Associated by Pegylated Peptide.

    Science.gov (United States)

    Ohta, Takahisa; Hashida, Yasuhiko; Yamashita, Fumiyoshi; Hashida, Mitsuru

    2016-01-01

    A novel sustained release formulation of mitomycin C (MMC) was developed by employing single-walled carbon nanotubes (SWCNTs) wrapped by designed peptide with polyethylene glycol (PEG) modification (pegylation) as a nano-scale molecular platform. The amino groups of polycationic and amphiphilic H-(-Cys-Trp-Lys-Gly-)(-Lys-Trp-Lys-Gly-)6-OH [CWKG(KWKG)6] peptide associated with SWCNTs were modified using PEG with 12 units (PEG12) to improve the dispersion stability of the composite. Then thiol groups of peptide were conjugated with MMC using N-ε-maleimidocaproic acid (EMCA) as a linker via transformation of aziridine group of MMC. The obtained SWCNTs-CWKG(KWKG)6-(PEG)12-C6-MMC composites particularly that with 13.6% PEG modification extent of amino groups, showed good dispersion stability both in water and in a cell culture medium for 24 h. The release of MMC from SWCNTs-CWKG(KWKG)6-(PEG)12-C6-MMC was confirmed to follow first-order kinetics being accelerated by the pH increase in good agreement with the results observed for MMC-dextran conjugate with the same conjugation structure. The SWCNTs-CWKG(KWKG)6-(PEG)12 composite exhibited a considerably low cytotoxicity against cultured human lung adenocarcinoma epithelial cell line (A549). In contrast, SWCNTs-CWKG(KWKG)6-(PEG)12-C6-MMC demonstrated delayed but relatively corresponding antitumor activity with free MMC at the same concentration. The results suggested the potential role of SWCNTs-CWKG(KWKG)6-(PEG)12 as a carrier for a controlled release drug delivery system (DDS).

  11. Development of novel sustained release matrix pellets of betahistine dihydrochloride: effect of lipophilic surfactants and co-surfactants.

    Science.gov (United States)

    Shamma, Rehab Nabil; Basalious, Emad B; Shoukri, Raguia

    2012-01-01

    Sustained release matrix pellets of the freely water soluble drug, betahistine dihydrochloride (BH), were prepared using freeze pelletization technique. Different waxes and lipids (cetyl alcohol, beeswax, glyceryl tripalmitate (GTP) and glyceryl tristearate) were evaluated for the preparation of matrix pellets. A D-optimal design was employed for the optimization and to explore the effect of drug loading (X(1)), concentration of lipophilic surfactant (X(2)), concentration of co-surfactant (X(3)) and wax type (X(4)) on the release extent of the drug from matrix pellets. The entrapment efficiency (Y(1)), pellet diameter (Y(2)), and the percentage drug released at given times were selected as dependent variables. Results revealed a significant impact of all independent variables on drug release from the formulated pellets. The lipophilic surfactant significantly increased both the entrapment efficiency and the in vitro drug release and significantly decreased the pellet size. The optimized BH-loaded pellets were composed of 19.95% drug loading, 9.95% Span(®) 80 (surfactant), 0.25% Capmul(®) (co-surfactant) using glyceryl tripalmitate as a matrix former. The release profiles of the drug from hard gelatin capsule containing optimized pellets equivalent to 32 mg BH was similar to that of target release model for once-daily administration based on similarity factor. It could be concluded that a promising once-daily capsule containing sustained release pellets of BH was successfully designed.

  12. 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.

  13. Development and evaluation in vitro and in vivo of injectable hydrolipidic gels with sustained-release properties for the management of articular pathologies such as osteoarthritis.

    Science.gov (United States)

    Réeff, Jonathan; Oprenyeszk, Frederic; Franck, Thierry; Goole, Jonathan; De Vriese, Carine; Serteyn, Didier; Henrotin, Yves; Amighi, Karim

    2015-07-25

    This study aimed to evaluate glycerol monooleate (GMO) as a carrier to develop viscoelastic and injectable sustained-release drug delivery systems. The potential pro- and antioxidant activity of the developed hydrolipidic gels were evaluated by measuring the production of ROS by polymorphonuclear leukocytes (PMNs). In addition, the biocompatibility and effectiveness of two selected gel candidates were evaluated in vivo by evaluating the benefit of a single intraarticular injection of these new treatments in a model of osteoarthritis in rabbits. The in vitro study demonstrated that the carrier F1 did not have a pro-oxidative effect and even protected PMNs against natural auto-activation, regardless of the incorporation of either clonidine chlorhydrate or betamethasone dipropionate. The in vivo study demonstrated that F1 and F1-BDP induced a loss of cartilage quality in comparison to the control and reference groups but that the lesions of cartilage observed were generally mild, with not much full-depth erosion. Moreover, no exacerbating inflammation was observed when considering the synovial membranes and the PGE2 and CRP levels. These results seemed to demonstrate that the sustained-release formulation based on GMO could be well-tolerated after intraarticular injection. Moreover, it could have the potential to prevent inflammatory conditions while sustaining drug activity locally over weeks.

  14. Sustained release from hot-melt extruded matrices based on ethylene vinyl acetate and polyethylene oxide.

    Science.gov (United States)

    Almeida, A; Brabant, L; Siepmann, F; De Beer, T; Bouquet, W; Van Hoorebeke, L; Siepmann, J; Remon, J P; Vervaet, C

    2012-11-01

    The aim of the present study was to evaluate the importance of matrix flexibility of hot-melt extruded (HME) ethylene vinyl acetate (EVA) matrices (with vinyl acetate (VA) contents of 9%, 15%, 28% and 40%), through the addition of hydrophilic polymers with distinct swelling capacity. Polyethylene oxide (PEO 100K, 1M and 7M) was used as swelling agent and metoprolol tartrate (MPT) as model drug. The processability via HME and drug release profiles of EVA/MPT/PEO formulations were assessed. Solid state characteristics, porosity and polymer miscibility of EVA/PEO matrices were evaluated by means of DSC, X-ray tomography and Raman spectroscopy. The processability via HME varied according to the VA content: EVA 40 and 28 were extruded at 90°C, whereas higher viscosity EVA grades (EVA 15 and 9) required a minimum extrusion temperature of 110°C to obtain high-quality extrudates. Drug release from EVA matrices depended on the VA content, PEO molecular weight and PEO content, matrix porosity as well as pore size distribution. Interestingly, the interplay of PEO leaching, matrix swelling, water influx and changes in matrix porosity influenced drug release: EVA 40- and 28-based matrices extruded with PEO of higher MW accelerated drug release, whereas for EVA 15- and 9-based matrices, drug release slowed down. These differences were related to the distinct polymer flexibility imposed by the VA content (lower VA content presents higher crystallinity and less free movement of the amorphous segments resulting in a higher rigidity). In all cases, diffusional mass transport seems to play a major role, as demonstrated by mathematical modeling using an analytical solution of Fick's second law. The bioavailability of EVA 40 and 28 matrices in dogs was not significantly different, independent of PEO 7M concentration.

  15. A Case of Anaphylactic Reaction Following Matsutake Mushroom Ingestion: Demonstration of Histamine Release Reaction of Basophils

    OpenAIRE

    Takako Toda; Masao Yamaguchi; Yuko Nakase; Naoya Sugimoto; Maho Suzukawa; Hiroyuki Nagase; Ken Ohta

    2010-01-01

    Background: Matsutake mushroom is not recognized as a common food allergen. However, several case reports have suggested that this mushroom can induce anaphylaxis on rare occasions. Case Summary: We report a woman with bronchial asthma, who experienced two episodes of Matsutake-induced anaphylaxis. Both the prick-to-prick test and basophil histamine release test showed positive reactions to this mushroom in this patient, but not in control subjects. Discussion: Matsutake mushroom can, o...

  16. Gum Ghatti--a pharmaceutical excipient: development, evaluation and optimization of sustained release mucoadhesive matrix tablets of domperidone.

    Science.gov (United States)

    Gurpreetarora; Malik, Karan; Rana, Vikas; Singh, Inderbir

    2012-01-01

    The objective of this study was to extend the GI residence time of the dosage form and to control the release of domperidone using directly compressible sustained release mucoadhesive matrix (SRMM) tablets. A 2-factor centre composite design (CCD) was employed to study the influence of independent variables like gum ghatti (GG) (X1) and hydroxylpropylmethyl cellulose K 15M (HPMC K 15M) (X2) on dependent variable like mucoadhesive strength, tensile strength, release exponent (n), t50 (time for 50% drug release), rel(10 h) (release after 10 h) and rel(18 h) (release after 18 h). Tablets were prepared by direct compression technology and evaluated for tablet parametric test (drug assay, diameter, thickness, hardness and tensile strength), mucoadhesive strength (using texture analyzer) and in vitro drug release studies. The tensile strength and mucoadhesive strength were found to be increased from 0.665 +/- 0.1 to 1.591 +/- 0.1 MN/cm2 (Z1 to Z9) and 10.789 +/- 0.985 to 50.924 +/- 1.150 N (Z1 to Z9), respectively. The release kinetics follows first order and Hixson Crowell equation indicating drug release following combination of diffusion and erosion. The n varies between 0.834 and 1.273, indicating release mechanism shifts from non fickian (anomalous release) to super case II, which depict that drug follows multiple drug release mechanism. The t50 time was found to increase from 5 +/- 0.12 to 11.4 +/- 0.14 h (Z1 to Z9) and release after 10 and 18 h decreases with increasing concentration of both polymers concluding with release controlling potential of polymers. The accelerated stability studies were performed on optimized formulation as per ICH guideline and the result showed that there was no significant change in tensile strength, mucoadhesive strength and drug assay.

  17. 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...

  18. OTO-104: a sustained-release dexamethasone hydrogel for the treatment of otic disorders.

    Science.gov (United States)

    Piu, Fabrice; Wang, Xiaobo; Fernandez, Rayne; Dellamary, Luis; Harrop, Anne; Ye, Qiang; Sweet, Jenifer; Tapp, Rachel; Dolan, David F; Altschuler, Richard A; Lichter, Jay; LeBel, Carl

    2011-01-01

    To investigate whether OTO-104, a poloxamer-based hydrogel containing micronized dexamethasone for intratympanic delivery, can provide long-lasting inner ear exposure and be well tolerated. OTO-104 was administered intratympanically to guinea pigs and sheep, and its pharmacokinetic and toxicity profiles were examined. After a single intratympanic injection of OTO-104 (from 0.6% to 20%, w/w), significant and prolonged exposure to dexamethasone in the inner ear was observed. Increasing the concentration of OTO-104 resulted in higher perilymph drug levels as well as a more prolonged duration of exposure. At the highest dose, therapeutic perilymph levels of dexamethasone could be sustained over 3 months in guinea pigs and more than 1 month in sheep. A toxicologic evaluation was conducted, including assessments of middle and inner ear function and physiology, as well as appraisal of local and systemic toxicity. A small and transient shift in hearing threshold was observed, most probably conductive in nature. No significant histologic changes in middle or inner ear tissues were noted. Although macroscopically mild erythema/inflammation was documented in a subset of guinea pigs treated with 20% OTO-104, the nature and the severity of these changes were not different between the poloxamer vehicle, saline, and 20% OTO-104 groups. No evidence of acute dermal toxicity, delayed hypersensitivity, or systemic adverse effects was found. OTO-104 is a novel proprietary therapeutic delivery system that can achieve prolonged, sustained release of dexamethasone within the inner ear fluids. The administration of this clinical candidate formulation via intratympanic injection is expected to be well tolerated both locally and systemically.

  19. A comparative pharmacokinetic and dynamic evaluation of alprazolam sustained-release, bromazepam, and lorazepam.

    Science.gov (United States)

    Busto, U E; Kaplan, H L; Wright, C E; Gomez-Mancilla, B; Zawertailo, L; Greenblatt, D J; Sellers, E M

    2000-12-01

    Sustained-release (SR) alprazolam may facilitate compliance with oral benzodiazepine treatment of panic disorders that currently requires doses administered three or four times daily. To compare the pharmacokinetic, psychomotor performance, and subjective effects of alprazolam SR (1.5 mg), bromazepam (3 mg taken three times daily), and lorazepam (1 mg taken three times daily), 13 male volunteers (aged 20-45 years) randomly received on four separate occasions one of these medications or placebo. Once before and 11 times after drug administration, the subjects were tested using psychomotor performance tests (manual tracking and digit-symbol substitution test [DSST]) and computerized questionnaires (such as the Tufts University Benzodiazepine Scale [TUBS], the Addiction Research Center Inventory, and the visual analog scales) to determine the subjective effects of the drugs. Blood samples for the determination of the plasma levels of the drugs were collected before and 17 times after the drug was administered. A peak plateau of plasma alprazolam began approximately 6 hours after the dose, which was later than the initial peaks for lorazepam and bromazepam (1-2 hours after the dose). Once this plateau had begun, alprazolam SR sustained that concentration better than did the other two formulations. Of the 10 measures on which the response averaged for the first 14 hours differed among drugs (p bromazepam differed from placebo on two measures, lorazepam on four (including DSST Performance and TUBS Sedation), and alprazolam SR on nine (including all four affected by lorazepam). Lorazepam and alprazolam, but not bromazepam, produced significantly more sedation than placebo. The doses of the three drugs were not equipotent in sedation and mood effects. None of the drugs tested differed from placebo on measures relevant to abuse liability.

  20. Decreased absorption as a possible cause for the lower bioavailability of a sustained-release propranolol.

    Science.gov (United States)

    Takahashi, H; Ogata, H; Warabioka, R; Kashiwada, K; Ohira, M; Someya, K

    1990-03-01

    The influence of sustained absorption on the oral availability of propranolol (P) and the metabolic disposition of P were investigated by obtaining the partial metabolic clearances (CLm) following long-acting P (LA) dosing in comparison with the conventional propranolol tablet (CP). Ten healthy volunteers were given a single oral dose of an LA capsule (60 mg) and CP (20 mg x 3) using a crossover design. Blood and urine samples were collected over 24- and 48-h postdose periods, respectively. Concentrations of P, propranolol glucuronide (PG), 4-hydroxypropranolol (4P), 4-hydroxypropranolol glucuronide (4PG), 4-hydroxypropranolol sulfate (4PS), and naphthoxylactic acid (NLA) were determined by HPLC with fluorescence and UV detection. Significant differences were observed between LA and CP in the area under the plasma concentration-time curves (AUCs) for P, PG, and NLA and in the amounts excreted into urine (Ae) for all measured metabolites (i.e., PG, 4P, 4PG, 4PS, and NLA). The parallel decrease of the AUC for P and the excreted amounts of all measured metabolites following LA dosing resulted in partial metabolic clearances (CLm) and renal clearances (CL) for P and its metabolites that were similar to those observed for CP. Therefore, the hepatic metabolism of P would not be affected by the slower absorption at a single oral dose of 60 mg. These results indicate that the poor absorption of P from the gastrointestinal tract might be one of the factors causing the low bioavailability of P observed after administration of the sustained-release formulation.

  1. Amphiphilic chitosan derivatives-based liposomes: synthesis, development, and properties as a carrier for sustained release of salidroside.

    Science.gov (United States)

    Peng, Hailong; Li, Wenjian; Ning, Fangjian; Yao, Lihua; Luo, Mei; Zhu, Xuemei; Zhao, Qiang; Xiong, Hua

    2014-01-22

    A novel amphiphilic chitosan derivative of N,N-dimethylhexadecyl carboxymethyl chitosan (DCMCs) was synthesized. The structure of DCMCs was confirmed via FT-IR and (1)H NMR, and the critical micelle concentration (CMC) was investigated by fluorescence spectroscopy. The results indicated that DCMCs has hydrophilic carboxyl and hydrophobic methylene groups and the CMC value was 23.00 mg·L(-1). The polymeric liposomes (DCMCs/cholesterol liposomes, DC-Ls) were developed, and its properties were evaluated. The DC-Ls exhibited multilamellar spheres with positive charge (+73.30 mV), narrow size distribution (PDI = 0.277), and good crystal properties. Salidroside was first to encapsulate into DC-Ls. Compared with traditional liposomes (phosphatidylcholine/cholesterol liposome, PC-Ls), DC-Ls showed higher encapsulation efficiency (82.46%) and slower sustained release rate. The in vitro salidroside release from DC-Ls was governed by two distinct stages (i.e., burst release and sustained release) and was dependent on the pH of the release medium. The case II transport and case I Fichian diffusion were the main release mechanisms for the entire release procedure. These results indicated that DC-Ls may be a potential carrier system for the production of functional foods that contain salidroside or other bioactive food ingredients.

  2. 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

  3. Pharmacokinetics and pharmacodynamics of a sustained-release dexamethasone intravitreal implant.

    Science.gov (United States)

    Chang-Lin, Joan-En; Attar, Mayssa; Acheampong, Andrew A; Robinson, Michael R; Whitcup, Scott M; Kuppermann, Baruch D; Welty, Devin

    2011-01-05

    To determine the pharmacokinetics and pharmacodynamics of a sustained-release dexamethasone (DEX) intravitreal implant (Ozurdex; Allergan, Inc.). Thirty-four male monkeys (Macaca fascicularis) received bilateral 0.7-mg DEX implants. Blood, vitreous humor, and retina samples were collected at predetermined intervals up to 270 days after administration. DEX was quantified by liquid chromatography-tandem mass spectrometry, and cytochrome P450 3A8 (CYP3A8) gene expression was analyzed by real-time reverse transcription-polymerase chain reaction. DEX was detected in the retina and vitreous humor for 6 months, with peak concentrations during the first 2 months. After 6 months, DEX was below the limit of quantitation. The C(max) (T(max)) and AUC for the retina were 1110 ng/g (day 60) and 47,200 ng · d/g, and for the vitreous humor were 213 ng/mL (day 60) and 11,300 ng · d/mL, respectively. The C(max) (T(max)) of DEX in plasma was 1.11 ng/mL (day 60). Compared with the level in the control eyes (no DEX implant), CYP3A8 expression in the retina was upregulated threefold up to 6 months after injection of the implant (0.969 ± 0.0565 vs. 3.07 ± 0.438; P < 0.05 up to 2-month samples). The in vivo release profile of the DEX implant in an animal eye was similar to the pharmacokinetics achieved with pulse administration of corticosteroids (high initial drug concentration, followed by a prolonged period of low concentration). These results are consistent with those in clinical studies supporting the use of the DEX implant for the extended management of posterior segment diseases.

  4. Mucoadhesive amorphous solid dispersions for sustained release of poorly water soluble drugs.

    Science.gov (United States)

    LaFountaine, Justin S; Prasad, Leena Kumari; Miller, Dave A; McGinity, James W; Williams, Robert O

    2017-04-01

    The oral delivery of mucoadhesive patches has been shown to enhance the absorption of large molecules such as peptides. We hypothesized that this mechanism could have utility for poorly soluble small molecules by utilizing a mucoadhesive polymer as the matrix for an amorphous solid dispersion. Binary dispersions of itraconazole and carbomer (Carbopol 71G) were prepared utilizing a thermokinetic mixing process (KinetiSol Dispersing) and the physicochemical properties were investigated by powder X-ray diffraction, calorimetry, and liquid chromatography. Adhesion of the dispersions to freshly excised porcine intestine was investigated with a texture analyzer. Minitablets were compressed from the optimal dispersion and further investigated in vitro and in vivo in rats. Thermokinetic mixing successfully processed amorphous dispersions up to 30% drug loading and each dispersion exhibited works of adhesion that were approximately an order of magnitude greater than a negative control in vitro. Ethylcellulose (EC) coated and uncoated minitablets prepared with the 30% drug load dispersion were delivered orally to rats and exhibited sustained release characteristics, with overall bioavailability greater for the uncoated minitablets compared to the EC-coated minitablets, similar to the rank order observed in our in vitro dissolution experiments. Necropsy studies showed that minitablets delivered with enteric-coated capsules targeted release to the distal small intestine and adhered to the intestinal mucosa, but the rat model presented limitations with respect to evaluating the overall performance. Based on the in vitro and in vivo results, further investigations in larger animals are a logical next step where fluid volumes, pH, and transit times are more favorable for the evaluated dosage forms.

  5. Plant extract synthesized PLA nanoparticles for controlled and sustained release of quercetin: a green approach.

    Directory of Open Access Journals (Sweden)

    Avnesh Kumari

    Full Text Available BACKGROUND: Green synthesis of metallic nanoparticles (NPs has been extensively carried out by using plant extracts (PEs which have property of stabilizers/emulsifiers. To our knowledge, there is no comprehensive study on applying a green approach using PEs for fabrication of biodegradable PLA NPs. Conventional methods rely on molecules like polyvinyl alcohol, polyethylene glycol, D-alpha-tocopheryl poly(ethylene glycol 1000 succinate as stabilizers/emulsifiers for the synthesis of such biodegradable NPs which are known to be toxic. So, there is urgent need to look for stabilizers which are biogenic and non-toxic. The present study investigated use of PEs as stabilizers/emulsifiers for the fabrication of stable PLA NPs. Synthesized PLA NPs through this green process were explored for controlled release of the well known antioxidant molecule quercetin. METHODOLOGY/PRINCIPAL FINDINGS: Stable PLA NPs were synthesized using leaf extracts of medicinally important plants like Syzygium cumini (1, Bauhinia variegata (2, Cedrus deodara (3, Lonicera japonica (4 and Eleaocarpus sphaericus (5. Small and uniformly distributed NPs in the size range 70±30 nm to 143±36 nm were formed with these PEs. To explore such NPs for drugs/ small molecules delivery, we have successfully encapsulated quercetin a lipophilic molecule on a most uniformly distributed PLA-4 NPs synthesized using Lonicera japonica leaf extract. Quercetin loaded PLA-4 NPs were observed for slow and sustained release of quercetin molecule. CONCLUSIONS: This green approach based on PEs mediated synthesis of stable PLA NPs pave the way for encapsulating drug/small molecules, nutraceuticals and other bioactive ingredients for safer cellular uptake, biodistribution and targeted delivery. Hence, such PEs synthesized PLA NPs would be useful to enhance the therapeutic efficacy of encapsulated small molecules/drugs. Furthermore, different types of plants can be explored for the synthesis of PLA as well

  6. Long-Term Sustained Release from a Biodegradable Photo-Cross-Linked Network for Intraocular Corticosteroid Delivery.

    Science.gov (United States)

    Amsden, Brian G; Marecak, Dale

    2016-09-06

    Intravitreal sustained delivery of corticosteroids such as dexamethasone is an effective means of treating a number of ocular diseases, including diabetic retinopathy, uveitis, and age-related or diabetic macular edema. There are currently marketed devices for this purpose, yet only one, Ozurdex, is degradable. In vitro release of dexamethasone from the Ozurdex device is limited to approximately 30 days, however. It was the objective of this study to examine the potential for prolonged and sustained release of a corticosteroid in vitro from a degradable polymer prepared from terminally acrylated star co- and ter-prepolymers composed of d,l-lactide, ε-caprolactone, and trimethylene carbonate co-photo-cross-linked with poly(ethylene glycol) diacrylate. Through manipulation of the network polymer glass transition temperature and degradation rate, a sustained release of triamcinolone was achieved, with an estimated release duration greater than twice that of the Ozurdex system. Moreover, a period of nearly constant release was obtained using a network prepared from 5000 Da star-poly(trimethylene carbonate-co-d,l-lactide) triacrylate (3:1 trimethylene carbonate:d,l-lactide) co-cross-linked with 700 Da poly(ethylene glycol diacrylate). These formulations show promise as implantable, intravitreal corticosteroid delivery devices.

  7. Characterization and In Vitro Sustained Release of Silibinin from pH Responsive Carbon Nanotube-Based Drug Delivery System

    Directory of Open Access Journals (Sweden)

    Julia M. Tan

    2014-01-01

    Full Text Available The objective of the present study was to develop and characterize an in vitro sustained release formulation of silibinin (SB using commercially available carboxylated multiwalled carbon nanotubes (COOH-MWCNTs and to investigate cytotoxicity action of the synthesized nanohybrid (SB-MWCNTs. The resulting nanohybrid was characterized with Fourier transform infrared (FTIR, Raman spectroscopy, thermogravimetric analysis (TGA, ultraviolet-visible spectrophotometry (UV-Vis, scanning electron microscopy (SEM, and transmission electron microscopy (TEM. FTIR, Raman spectroscopy, and TGA analysis confirmed the adsorption of SB molecules to the COOH-MWCNTs. The release of SB from the COOH-MWCNTs nanocarrier was found to be sustained and pH-dependent. The maximum percentage release of SB from the nanocarrier reached approximately 96.6% and 43.1% within 1000 minutes when exposed to pH 7.4 and pH 4.8 solutions, respectively. It was observed that the release of kinetic behaviour of SB from the MWCNTs nanocarrier conformed well to pseudo-second order kinetic model. The obtained MTT result showed that the SB-MWCNTs exhibited enhanced cytotoxicity to human cancer cell lines in comparison with free SB at lower concentrations. These results suggest that SB-MWCNTs nanohybrid may be a promising nanodrug delivery system with sustained release property for the treatment of cancers.

  8. Novel preparation method for sustained-release PLGA microspheres using water-in-oil-in-hydrophilic-oil-in-water emulsion

    Directory of Open Access Journals (Sweden)

    Hong X

    2013-07-01

    Full Text Available Xiaoyun Hong,1,2,* Liangming Wei,3,* Liuqing Ma,2 Yinghui Chen,4 Zhenguo Liu,1 Weien Yuan2,* 1Department of Neurology, Xinhua Hospital affiliated to Shanghai JiaoTong University, School of Medicine, Shanghai, People's Republic of China; 2School of Pharmacy, Shanghai JiaoTong University, 3Key Laboratory for Thin Film and Microfabrication Technology, Ministry of Education, Research Institute of Micro/Nanometer Science and Technology, Shanghai JiaoTong University, Shanghai, People's Republic of China; 4Department of Neurology, Jinshan Hospital, Fudan University, Shanghai, People's Republic of China *These authors contributed equally to this work Abstract: An increasing number of drugs are needing improved formulations to optimize patient compliance because of their short half-lives in blood. Sustained-release formulations of drugs are often required for long-term efficacy, and microspheres are among the most popular ones. When drugs are encapsulated into microsphere formulations, different methods of preparation need to be used according to specific clinical requirements and the differing physicochemical characteristics of individual drugs. In this work, we developed a novel method for sustained-release drug delivery using a water-in-oil-in-hydrophilic oil-in-water (w/o/oh/w emulsion to encapsulate a drug into poly(lactic-co-glycolic acid (PLGA microspheres. Different effects were achieved by varying the proportions and concentrations of hydrophilic oil and PLGA. Scanning electron and optical microscopic images showed the surfaces of the microspheres to be smooth and that their morphology was spherical. Microspheres prepared using the w/o/oh/w emulsion were able to load protein efficiently and had sustained-release properties. These results indicate that the above-mentioned method might be useful for developing sustained-release microsphere formulations in the future. Keywords: protein, microspheres, water-in-oil-in-hydrophilic oil

  9. 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.

  10. Pharmacokinetics of a sustained-release dexamethasone intravitreal implant in vitrectomized and nonvitrectomized eyes.

    Science.gov (United States)

    Chang-Lin, Joan-En; Burke, James A; Peng, Qing; Lin, Ton; Orilla, Werhner C; Ghosn, Corine R; Zhang, Kai-Ming; Kuppermann, Baruch D; Robinson, Michael R; Whitcup, Scott M; Welty, Devin F

    2011-06-28

    To evaluate dexamethasone pharmacokinetics after implantation of a sustained-release dexamethasone (DEX) intravitreal implant in nonvitrectomized and vitrectomized eyes. The right eyes of 25 rabbits underwent vitrectomy; contralateral eyes served as nonvitrectomy controls. The 0.7-mg DEX implant was injected into both eyes, and drug concentrations were determined in the vitreous humor and retina for 31 days (on days 2, 8, 15, 22, and 31). DEX was present in nonvitrectomized and vitrectomized eyes for at least 31 days. There were no statistically significant differences in DEX concentration between nonvitrectomized and vitrectomized eyes at any time point (P > 0.05). The maximum concentration of DEX in nonvitrectomized versus vitrectomized eyes for vitreous humor was 791 ng/mL (day 22) versus 731 ng/mL (day 22), respectively, and for retina it was 4110 ng/mL (day 15) versus 3670 ng/mL (day 22), respectively. Mean absorption (AUC(0-tlast)) of dexamethasone in nonvitrectomized and vitrectomized eyes was not different for both the vitreous humor (13,600 vs. 15,000 ng/day/mL; P = 0.73) and retina (67,600 vs. 50,200 ng/day/mL; P = 0.47). The vitreoretinal pharmacokinetic profiles were similar between nonvitrectomized and vitrectomized eyes. These observations are consistent with clinical findings of the DEX implant in patients who have undergone vitrectomy and should reduce concerns about the use of the DEX implant in eyes that have undergone vitrectomy.

  11. 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.

  12. 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.

  13. Enhanced bone tissue formation by alginate gel-assisted cell seeding in porous ceramic scaffolds and sustained release of growth factor.

    Science.gov (United States)

    Florczyk, Stephen J; Leung, Matthew; Jana, Soumen; Li, Zhensheng; Bhattarai, Narayan; Huang, Jerry I; Hopper, Richard A; Zhang, Miqin

    2012-12-01

    Increasing cell seeding efficiency in a tissue engineering construct can enhance cellular activity and tissue formation in vivo. Here, we demonstrate the use of alginate gel as a secondary phase material in 3D porous β-tricalcium phosphate scaffolds to improve cell seeding and provide controlled release of growth factors for bone tissue engineering. Cells were seeded in scaffolds in three ways: conventional seeding (CS), alginate gel-assisted seeding (GS), and alginate GS with bone morphogenetic protein-2 (BMP-2, GSB). In vitro study with MG-63 cells showed that cell seeding efficiency and cell population 1 week after seeding were significantly elevated in GS and GSB samples compared to CS samples. The GSB system demonstrated a sustained, steady release of BMP-2 over 2 weeks. In vivo, scaffolds seeded with rat mesenchymal stem cells were implanted ectopically into Sprague-Dawley rats for 8 weeks. GS and GSB samples exhibited improved osteogenic activity, with the GSB samples inducing the greatest osteocalcin and osteoid deposition. This study suggests that the alginate gel-assisted cell seeding increases seeding efficiency and allows for sustained release of growth factors. The use of the secondary phase polymer bolsters bone formation in vivo and has the potential for improving outcome in other tissue engineering applications.

  14. FORMULATION AND IN VITRO EVALUATION OF ARAUCARIA BIDWILLI GUM-BASED SUSTAIN RELEASE MATRIX TABLETS OF DICLOFENAE SODIUM

    Directory of Open Access Journals (Sweden)

    J. ASHOK KUMAR, M.RAJESH, S.MYTHIESH KUMAR,T. GIRIRAJ KULKARNI, V.GOPAL

    2013-10-01

    Full Text Available A gel forming Polysaccharide gum obtained form the bark of Araucaria bidwilli was employed as a matrix sustained release tablet formulation of Diclofenac sodium (a non steroidal anti inflammatory agent. The effect of Araucaria bidwilli gum (Natural and Synthetic polymer Hydroxypropyl methyl cellulose (HPMC K4 M on the release of Diclofenac sodium was studied. The FT-IR spectroscopic studies of drug, gum and mixture indicated no chemical interaction. Six formulations were prepared by wet granulation method containing Araucaria bidwilli gum powder concentration 10% 20% & 30% w\\w and 10% 20% &30% w\\w of HPMC K4 M with sufficient volume of granulating agent Polyvinyl pyrrolene (PVP K 30, Avicel pH101 as diluents, Magnesium stearate and Aerosil is used lubricant and glidant respectively.This study was carried out to find out the difference between synthetic and natural gum and whether synthetic gum can be replaced by natural gums. Physical and technological studies of granules and tablets were compliance with Pharmacopoial standards.The drug release increased with Araucaria bidwilli gum when compared to synthetics polymer concentration .The value of release exponent were found to be almost straight line and regression coefficient value between 0.938 and 0.998.This implies that the release mechanism is diffusion. Formulation F3 ( contained 30% w\\w Araucaria bidwilli gum met the desired requirements for a sustained release dosage form.

  15. Double-walled microspheres for the sustained release of a highly water soluble drug: characterization and irradiation studies.

    Science.gov (United States)

    Lee, Teng Huar; Wang, Jianjun; Wang, Chi-Hwa

    2002-10-30

    Composite double-walled microspheres with biodegradable poly(L-lactic acid) (PLLA) shells and poly(D,L-lactic-co-glycolic acid) (PLGA) cores were fabricated with highly water-soluble etanidazole entrapped within the core as solid crystals. This paper discusses the characterization, in vitro release and the effects of irradiation on this class of microsphere. Through the variation of polymer mass ratios, predictable shell and core dimensions could be fabricated and used to regulate the release rates. A direct and simple method was devised to determine the composition of the shell and core polymer based on the different solubilities of the polymer pair in ethyl acetate. A distribution theory based on solubility parameter explains why highly hydrophilic etanidazole has the tendency to be distributed consistently to the more hydrophilic polymer. Release profiles for normal double-walled samples have about 80% of drug released over 10 days after the initial time lag, while for irradiated double-walled samples, the sustained release lasted for more than 3 weeks. Although sustained release was short of the desired 6-8 weeks required for therapy, a low initial burst of less than 5% and time lags that can be manipulated, allows for administration of these microspheres together with traditional ones to generate pulsatile or new type of releases. The effects of irradiation were also investigated to determine the suitability of these double-walled microspheres as delivery devices to be used in conjunction with radiotherapy. Typical therapeutic dosage of 50 Gy was found to be too mild to have noticeable effects on the polymer and its release profiles, while, sterilization dosages of 25 kGy, lowered the glass transition temperatures and crystalline melting point, indirectly indicating a decrease in molecular weight. This accelerated degradation of the polymer, hence releasing the drug.

  16. Demonstration of Combined Food and Landscape Waste Composting at Fort Leonard Wood, MO: Fort Leonard Wood Installation Strategic Sustainable Plan

    Science.gov (United States)

    2016-01-01

    university postconsumer food wastes . Compost Science and Utilization 6:75-81. Epstein, E. 1997. The Science of Composting. Lancaster, PA: Technomic...Sustainability Innovations (CASI) ERDC/CERL TR-16-1 January 2016 Demonstration of Combined Food and Landscape Waste Composting at Fort Leonard Wood, MO...amendments and organic fertilizers using simple composting technologies, less than 3% of food wastes are recovered and recycled and the remainder are

  17. Long-term sustained release of salicylic acid from cross-linked biodegradable polyester induces a reduced foreign body response in mice.

    Science.gov (United States)

    Chandorkar, Yashoda; Bhaskar, Nitu; Madras, Giridhar; Basu, Bikramjit

    2015-02-09

    There has been a continuous surge toward developing new biopolymers that exhibit better in vivo biocompatibility properties in terms of demonstrating a reduced foreign body response (FBR). One approach to mitigate the undesired FBR is to develop an implant capable of releasing anti-inflammatory molecules in a sustained manner over a long time period. Implants causing inflammation are also more susceptible to infection. In this article, the in vivo biocompatibility of a novel, biodegradable salicylic acid releasing polyester (SAP) has been investigated by subcutaneous implantation in a mouse model. The tissue response to SAP was compared with that of a widely used biodegradable polymer, poly(lactic acid-co-glycolic acid) (PLGA), as a control over three time points: 2, 4, and 16 weeks postimplantation. A long-term in vitro study illustrates a continuous, linear (zero order) release of salicylic acid with a cumulative mass percent release rate of 7.34 × 10(-4) h(-1) over ∼1.5-17 months. On the basis of physicochemical analysis, surface erosion for SAP and bulk erosion for PLGA have been confirmed as their dominant degradation modes in vivo. On the basis of the histomorphometrical analysis of inflammatory cell densities and collagen distribution as well as quantification of proinflammatory cytokine levels (TNF-α and IL-1β), a reduced foreign body response toward SAP with respect to that generated by PLGA has been unambiguously established. The favorable in vivo tissue response to SAP, as manifest from the uniform and well-vascularized encapsulation around the implant, is consistent with the decrease in inflammatory cell density and increase in angiogenesis with time. The above observations, together with the demonstration of long-term and sustained release of salicylic acid, establish the potential use of SAP for applications in improved matrices for tissue engineering and chronic wound healing.

  18. FORMULATION, OPTIMIZATION AND EVALUATION OF BILAYERED TABLETS OF AMLODIPINE BESILATE AS IMMEDIATE RELEASE AND METOPROLOL SUCCINATE AS SUSTAINED RELEASE

    OpenAIRE

    Arup Ratan Deb; Vivek Keshri; Padmakana Malakar

    2013-01-01

    The purpose of the study was to develop a bilayer tablet of Amlodipine besilate (IR) and Metoprolol succinate (SR) having different release pattern, which is indicated for the management of hypertension. The study was planned in three stages. In the first stage six batches (A1, A2, A3, A4, A5 and A6) of immediate release tables of Amlodipine besilate was prepared by direct compression method using sodium starch glycolate and pre-gelatinised starch as super disintegrant. In the second stage, s...

  19. Central nervous system effects of moxonidine experimental sustained release formulation in patients with mild to moderate essential hypertension

    Science.gov (United States)

    Kemme, Michiel J B; Post, Jeroen P vd; Schoemaker, Rik C; Straub, Matthias; Cohen, Adam F; van Gerven, Joop M A

    2003-01-01

    Objectives The primary aim was to demonstrate that moxonidine, given in an experimental sustained release (SR) formulation, had no clinically relevant central nervous system (CNS) effects after 4 weeks of treatment. A clinically relevant CNS effect was predefined as more than 45° s−1 reduction in saccadic peak velocity (SPV), corresponding to the effects of one night's sleep deprivation. Methods In a randomized, double-blind fashion, 35 patients with mild to moderate essential hypertension received placebo run-in medication for 2 weeks, followed by 4 weeks’ moxonidine sustained release (1.5 mg o.d.) or placebo. On the first day and 1 and 4 weeks following the start of treatment, blood pressure was measured and CNS effects were assessed using SPV, visual analogue scales and EEG. Results On day 1 there was a significant, but not clinically relevant, reduction in the time-corrected area under the effect curve (AUEC) for SPV in the moxonidine group compared with placebo [difference of 38° s−1; 95% confidence interval (CI) 23, 52]. This difference was no longer significant after one (9° s−1; 95% CI −17, 35) and 4 weeks (6.9° s−1; 95% CI −16, 30). Visual analogue scales for alertness showed similar results. A decrease in EEG α- and β-power and an increase in δ-power were only found on day 1 of moxonidine treatment. The AUEC for systolic/diastolic blood pressure relative to placebo was 23 (95% CI 17, 29)/13 (9, 16) mmHg lower on day 1 and remained reduced by 20 (11, 30)/12 (6, 17) and 15 (6, 25)/9 (3, 15) mmHg after 1 and 4 weeks’ moxonidine treatment. Conclusions Four weeks’ treatment with an experimental SR formulation resulted in tolerance to CNS effects (equivalence to placebo) while blood pressure-lowering effects remained adequate. The tolerance to CNS effects was already observed after 1 week of treatment. PMID:12814444

  20. Enhanced osteogenesis and angiogenesis by mesoporous hydroxyapatite microspheres-derived simvastatin sustained release system for superior bone regeneration

    Science.gov (United States)

    Yu, Wei-Lin; Sun, Tuan-Wei; Qi, Chao; Zhao, Hua-Kun; Ding, Zhen-Yu; Zhang, Zhi-Wang; Sun, Ben-Ben; Shen, Ji; Chen, Feng; Zhu, Ying-Jie; Chen, Dao-Yun; He, Yao-Hua

    2017-01-01

    Biomaterials with both excellent osteogenic and angiogenic activities are desirable to repair massive bone defects. In this study, simvastatin with both osteogenic and angiogenic activities was incorporated into the mesoporous hydroxyapatite microspheres (MHMs) synthesized through a microwave-assisted hydrothermal method using fructose 1,6-bisphosphate trisodium salt (FBP) as an organic phosphorous source. The effects of the simvastatin-loaded MHMs (S-MHMs) on the osteogenic differentiation of rat bone marrow mesenchymal stem cells (rBMSCs) and angiogenesis in EA.hy926 cells were investigated. The results showed that the S-MHMs not only enhanced the expression of osteogenic markers in rBMSCs but also promoted the migration and tube formation of EA.hy926 cells. Furthermore, the S-MHMs were incorporated into collagen matrix to construct a novel S-MHMs/collagen composite scaffold. With the aid of MHMs, the water-insoluble simvastatin was homogenously incorporated into the hydrophilic collagen matrix and presented a sustained release profile. In vivo experiments showed that the S-MHMs/collagen scaffolds enhanced the bone regeneration and neovascularization simultaneously. These results demonstrated that the water-insoluble simvastatin could be incorporated into the MHMs and maintained its biological activities, more importantly, the S-MHMs/collagen scaffolds fabricated in this study are of immense potential in bone defect repair by enhancing osteogenesis and angiogenesis simultaneously. PMID:28287178

  1. 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.

  2. Co-encapsulation and sustained-release of four components in ginkgo terpenes from injectable PELGE nanoparticles.

    Science.gov (United States)

    Han, Limei; Fu, Yan; Cole, Adam J; Liu, Jie; Wang, Jianxin

    2012-06-01

    It is difficult to develop injectable sustained delivery systems for herbal medicines because of their composition complexity. Encapsulating various compounds with different physiochemical properties and achieving their synchronized and sustained release seem too hard to realize. In this paper, an injectable nanoparticulate system based on an mPEG-PLGA-mPEG (PELGE) platform was prepared for co-encapsulation and sustained release of four active components (ginkgolides A, B, C and bilobalide) in Ginkgo biloba extract. Different carriers were screened by macrophage uptake experiment for their ability to be long-circulation. Drug loaded nanoparticles were prepared with 10% PEG(2000) modified PLGA by a co-precipitation method. The encapsulation efficiency of the total ginkgo terpenes (GT) in the optimal formulation was 78.84±2.06% with a loading dose of 11.90±0.31mg/150mg PELGE. The particles exhibited a spherical shape with a mean diameter of 123.3±44.0nm and zeta potential of -30.86±2.49mV. Sustained and synchronized release of the four components from PELGE nanoparticles was observed both in vitro and in vivo, which was mainly contributed to the long circulation of PEGylated nanoparticles and the slow degradation of PLGA. The half-life time of the four terpenoid compounds were also significantly improved by incorporation into PELGE nanoparticles. The results indicate that a PELGE nanoparticle is a promising carrier system for sustained and synchronized release of herbal medicines containing multiple components. Copyright © 2012 Elsevier B.V. All rights reserved.

  3. Sustained release of VEGF from PLGA nanoparticles embedded thermo-sensitive hydrogel in full-thickness porcine bladder acellular matrix

    Directory of Open Access Journals (Sweden)

    Song Hua

    2011-01-01

    Full Text Available Abstract We fabricated a novel vascular endothelial growth factor (VEGF-loaded poly(lactic-co-glycolic acid (PLGA-nanoparticles (NPs-embedded thermo-sensitive hydrogel in porcine bladder acellular matrix allograft (BAMA system, which is designed for achieving a sustained release of VEGF protein, and embedding the protein carrier into the BAMA. We identified and optimized various formulations and process parameters to get the preferred particle size, entrapment, and polydispersibility of the VEGF-NPs, and incorporated the VEGF-NPs into the (poly(ethylene oxide-poly(propylene oxide-poly(ethylene oxide (Pluronic® F127 to achieve the preferred VEGF-NPs thermo-sensitive gel system. Then the thermal behavior of the system was proven by in vitro and in vivo study, and the kinetic-sustained release profile of the system embedded in porcine bladder acellular matrix was investigated. Results indicated that the bioactivity of the encapsulated VEGF released from the NPs was reserved, and the VEGF-NPs thermo-sensitive gel system can achieve sol-gel transmission successfully at appropriate temperature. Furthermore, the system can create a satisfactory tissue-compatible environment and an effective VEGF-sustained release approach. In conclusion, a novel VEGF-loaded PLGA NPs-embedded thermo-sensitive hydrogel in porcine BAMA system is successfully prepared, to provide a promising way for deficient bladder reconstruction therapy.

  4. Preparation and pharmacokinetics in beagle dogs of once-a-day tetramethylpyrazine phosphate sustained-release pellets.

    Science.gov (United States)

    Yanyu, Xiao; Qineng, Ping; Zhigui, Su; Hongying, Li; Jiangxiu, Niu

    2012-03-01

    In this study, once-a-day tetramethylpyrazine phosphate (TMPP) sustained-release pellets were successfully prepared. The pellets cores were carried out in extrusion-spheronization machine and then coated in fluidized-bed. To optimize cumulative release profile, two different coating systems with the same the TMPP pellets cores were employed. The first coating system consisted of surlease, containing HPMC E5 (0.1% w/w), i.e., P1. The second coating system only consisted of surlease, i.e., P2. The two kinds of coating systems were both given coating levels in terms of weight gain of 10%. The resulted once-a-day TMPP sustained-release pellets (OTSP), the mixture of P1 and P2 with the weight proportion of 1:1, were filled in a capsule (150 mg TMPP/capsule). The relative bioavailability of OTSP was studied in six beagle dogs after oral administration using a commercial TMPP tablets as a reference. The C(max) and T(max) for OTSP and TMPP tablets were 213.06 ng/mL, 2.50 h and 3402.13 ng/mL, 0.33 h, respectively and the relative bioavailability of P3 was 97.18% compared with TMPP tablets. Based on the results, it was indicated that TMPP sustained-release pellets and TMPP conventional tablets were bioequivalent.

  5. 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.

  6. 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.

  7. THOUGHTS ON CONSTRUCTING THE DEMONSTRATING AREAS OF THE ECOLOGICAL REBUILDING AND ECONOMIC SUSTAINABLE DEVELOPMENT IN HEXI REGION

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Based on the field investigations, this paper analyzes systematically the achievements and problems of construct-ing the demonstrating areas of the ecological rebuilding and economic sustainable development in Hexi, Gansu Province,and then the thoughts on constructing the demonstrating areas are brought forward. It is considered that all kinds of ecologi-cal demonstrating areas should be merged in order to construct large-scale characterized demonstrating areas which go be-yond the district. In other words, in Hexi Region, Zhangye District should be constructed as the largest ecoagriculture demon-strating area of high technology; Wuwei District should be constructed as the largest ecological demonstrating area of agricultur-al comprehensive exploitation; JiuJia District, which is the shortened form of Jiuquan and Jiayuguan, should be construct-ed as the largest ecotourism demonstrating area; and Jinchang City should be constructed as the largest ecoindustry demonstrat-ing area. At the same time, the constructing pattern should be selected according to the actual circumstances; scienceand technology should be applied to construct the demonstrating areas and accelerate the industrialization in the big mar-ket. Additionally, it is important to smooth the constructing system and implement the flexible and efficacious running mecha-nism, and it is suggested that the committee should be organized to administer the ecological demonstrating areas in HexiRegion.

  8. 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

  9. Multiple-dose pharmacokinetics of fesoterodine sustained-release in healthy Korean volunteers.

    Science.gov (United States)

    Shin, Dongseong; Shin, Kwang-Hee; Lee, SeungHwan; Lim, Kyoung Soo; Cho, Joo-Youn; Jang, In-Jin; Shin, Sang-Goo; Yu, Kyung-Sang

    2012-10-01

    Fesoterodine is a pro-drug of the active metabolite 5-hydroxymethyl tolterodine (5-HMT), a muscarinic receptor antagonist. This study aimed to evaluate the safety profile and pharmacokinetic characteristics of multiple oral doses of sustained-release fesoterodine (fesoterodine SR) in healthy Korean males. A randomized, double-blind, placebo-controlled, multiple-dose study with two oral doses (4 mg and 8 mg) was conducted in healthy Korean male participants. The study drug was administered once daily for 5 days. The plasma concentration of 5-HMT was measured up to 72 hours after the last drug administration. The CYP2D6 genotype was analyzed using polymerase chain reaction (PCR) methods to assess the effect of genetic polymorphisms on the pharmacokinetic parameters. 20 participants completed the study. The mean (SD) areas under the plasma concentration-time curves during the dosing interval (AUCτ) of the 4 mg and 8 mg dose groups were 26.1 (8.0) and 64.2 (30.5) μg·h/ml and the mean peak concentrations (Cmax) were 2.6 (0.7) and 6.0 (2.0) μg/ml, respectively, at steady-state. The mean AUCτ and Cmax of 5-HMT increased in approximately the same proportion as the dose increased. Fesoterodine SR was well tolerated without any serious adverse events or abnormal clinical laboratory findings. Systemic 5-HMT exposure showed dose-proportional characteristics in the 4 mg to 8 mg dose range in healthy Korean males. Thus, 4 mg or 8 mg doses of fesoterodine SR taken once-daily were tolerable in healthy Korean males.

  10. Efficacy of Sustained-Release Buprenorphine in an Experimental Laparotomy Model in Female Mice.

    Science.gov (United States)

    Kendall, Lon V; Wegenast, Daniel J; Smith, Brian J; Dorsey, Kathryn M; Kang, Sooah; Lee, Na Young; Hess, Ann M

    2016-01-01

    Mice purportedly require dosing with the opioid buprenorphine (Bup-HCl) at least every 8 to 12 h to maintain an adequate plane of analgesia. Here we used an experimental laparotomy model to determine the clinical efficacy of sustained-release formulations of buprenorphine (Bup-SR) after surgery in mice. Female CD1 mice underwent laparotomy and received either Bup-SR (0.6 mg/kg), Bup-HCl (0.1 mg/kg every 12 h), or saline (every 12 h). Pain was assessed at 1, 3, 6, 12, 24, 48, and 72 h according to the frequency of several behaviors (general activity, wheel-running activity, rearing, grooming, wound licking, orbital tightening, and percentage of integrated nest material) and daily body weight. Over time, wheel running was increased and wound licking was decreased in Bup-SR-treated mice compared with Bup-HCl- and saline-treated mice. Compared with Bup-HCl- and saline-treated mice, Bup-SR-treated mice had increased general activity and percentage of integrated nest material and decreased orbital tightening for 1 to 6 h after surgery. The Bup-HCl- and saline-treated mice had similar general activity, orbital tightening scores, and wheel running activity. Rearing activity and body weight did not differ throughout the study, and none of the observed behaviors differed between groups at 24, 48, and 72 h after surgery. These results suggest that Bup-SR at 0.6 mg/kg provides adequate analgesia after laparotomy in mice and can be used as an alternative analgesic in this context. Furthermore, Bup-HCl at 0.1 mg/kg every 12 h may be inadequate in providing analgesia for abdominal procedures in mice.

  11. 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.

  12. Cubic phase nanoparticles for sustained release of ibuprofen formulation characterization and enhanced bioavailability study

    Directory of Open Access Journals (Sweden)

    Dian L

    2013-02-01

    Full Text Available Linghui Dian,1,2,* Zhiwen Yang,3,* Feng Li,1 Zhouhua Wang,1 Xin Pan,1 Xinsheng Peng,2 Xintian Huang,1 Zhefei Guo,1 Guilan Quan,1 Xuan Shi,1 Bao Chen,1 Ge Li,4 Chuanbin Wu1,41School of Pharmaceutical Sciences, Sun Yat-Sen University, University Town, Guangzhou, People’s Republic of China; 2School of Pharmaceutical Sciences, Guangdong Medical College, Dongguan, People’s Republic of China; 3Department of Gastroenterology, Songjiang Branch of the Affiliated First People’s Hospital of Shanghai Jiaotong University, Shanghai, People’s Republic of China; 4Guangdong Research Center for Drug Delivery Systems, Guangzhou, People’s Republic of China*These authors contributed equally to this workAbstract: In order to improve the oral bioavailability of ibuprofen, ibuprofen-loaded cubic nanoparticles were prepared as a delivery system for aqueous formulations. The cubic inner structure was verified by cryogenic transmission electron microscopy. With an encapsulation efficiency greater than 85%, the ibuprofen-loaded cubic nanoparticles had a narrow size distribution around a mean size of 238 nm. Differential scanning calorimetry and X-ray diffraction determined that ibuprofen was in an amorphous and molecular form within the lipid matrix. The in vitro release of ibuprofen from cubic nanoparticles was greater than 80% at 24 hours, showing sustained characteristics. The pharmacokinetic study in beagle dogs showed improved absorption of ibuprofen from cubic nanoparticles compared to that of pure ibuprofen, with evidence of a longer half-life and a relative oral bioavailability of 222% (P < 0.05. The ibuprofen-loaded cubic nanoparticles provide a promising carrier candidate with an efficient drug delivery for therapeutic treatment.Keywords: ibuprofen, cubic nanoparticles, oral drug delivery, bioavailability

  13. Sustained release of VH and rhBMP-2 from nanoporous magnesium-zinc-silicon xerogels for osteomyelitis treatment and bone repair.

    Science.gov (United States)

    Li, Fengqian; Wu, Wen; Xiang, Li; Weng, Gan; Hong, Hua; Jiang, Hong; Qian, Jun

    2015-01-01

    Nanoporous magnesium-zinc-silicon (n-MZS) xerogels with a pore size ∼4 nm, a surface area of 718 cm(2)/g, and a pore volume of 1.24 cm(3)/g were synthesized by a sol-gel method. The n-MZS xerogels had high capacity to load vancomycin hydrochloride (VH) and human bone morphogenetic protein-2 (rhBMP-2), after soaking in phosphate buffered saline (PBS) for 24 hours (1.5 and 0.8 mg/g, respectively). Moreover, the n-MZS xerogels exhibited the sustained release of VH and rhBMP-2 as compared with magnesium-zinc-silicon (MZS) xerogels without nanopores (showing a burst release). The VH/rhBMP-2/n-MZS system not only exhibited a good antibacterial property but also promoted the MG63 cell proliferation and differentiation demonstrating good bactericidal activity and cytocompatibility. The results suggested that n-MZS with larger surface area and high pore volume might be a promising carrier for loading and sustained release of VH and rhBMP-2. Hence, the VH/rhBMP-2/n-MZS system might be one of the promising biomaterials for osteomyelitis treatment and bone repair.

  14. 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.

  15. 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.

  16. In vivo imaging demonstrates ATP release from murine keratinocytes and its involvement in cutaneous inflammation after tape stripping.

    Science.gov (United States)

    Takahashi, Toshiya; Kimura, Yutaka; Niwa, Kazuki; Ohmiya, Yoshihiro; Fujimura, Taku; Yamasaki, Kenshi; Aiba, Setsuya

    2013-10-01

    Adenosine 5'-triphosphate (ATP) release from keratinocytes has been observed in various stress models in vitro, but studies demonstrating epidermal ATP release in vivo are limited. To visualize extracellular ATP (eATP) in vivo, we developed enhanced green-emitting luciferase immobilized on agarose beads (Eluc-agarose). Subcutaneous injection of Eluc-agarose together with ATP into the dorsal skin of BALB/c mice following intraperitoneal luciferin injection produced detectable and measurable bioluminescence using an in vivo imaging system. Using Eluc-agarose, we demonstrated in vivo that bright bioluminescence was observed from 1 to 20 minutes after repeated tape stripping of murine skin. This bioluminescence was suppressed by the local administration of apyrase. Eluc-agarose bioluminescence was observed only in tape-stripped skin with transepidermal water loss (TEWL) between 100 and 140 g m(2) h(-1), indicating a loss of bioluminescence with excessive tape stripping (TEWL>140 g m(-2) h(-1)). Histologically, tape-stripped skin with detectable eATP had a viable epidermis and a subepidermal neutrophil infiltrate, and administration of apyrase reduced the inflammatory infiltrate. Neither a viable epidermis nor an upper dermal neutrophil infiltrate was observed after excessive tape stripping. These results suggest that tape stripping prompts ATP release from viable keratinocytes, which facilitates inflammatory cell migration. Eluc-agarose may be useful in the in vivo detection of eATP in murine models of skin diseases.

  17. 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

  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

    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...... 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...

  19. 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...... measured using scintigraphic and manometric techniques. Isosorbide dinitrate did not change the area under the curve of gastric retention versus time, and did not influence the frequency of antral contractions as assessed at 15-min intervals or the integrated duodenal motility index, as recorded over...... consecutive 15-min periods. A 40 mg single dose of sustained-released isosorbide dinitrate does not seem to alter gastric emptying or gastroduodenal motility after a meal....

  20. 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.

  1. Sustained-release of Cyclosporin A pellets: preparation, in vitro release, pharmacokinetic studies and in vitro-in vivo correlation in beagle dogs.

    Science.gov (United States)

    Jiang, Dongmei; Zeng, Jin; Zhu, Yuan; Zhou, Guanghui; Deng, Wenwen; Xu, Ximing; Yu, Jiangnan

    2016-01-01

    The aim of this study was to develop Cyclosporin A (CsA) sustained-release pellets which could maintain CsA blood concentration within the therapeutic window throughout dosing interval and to investigate the in vitro-in vivo correlation (IVIVC) in beagle dogs. The CsA sustained-release pellets (CsA pellets) were prepared by a double coating method and characterized in vitro as well as in vivo. Consequently, the CsA pellets obtained were spherical in shape, with a desirable drug loading (7.18 ± 0.17 g/100 g), good stability and showed a sustained-release effect. The Cmax, Tmax and AUC0-24 of CsA pellets from the in vivo pharmacokinetics evaluation was 268.22 ± 15.99 ng/ml, 6 ± 0 h and 3205.00 ± 149.55 ng·h/ml, respectively. Compared with Neoral®, CsA pellets significantly prolonged the duration of action, reduced the peak blood concentration and could maintain a relatively high concentration level till 24 h. The relative bioavailability of CsA pellets was 125.68 ± 5.37% that of Neoral®. Moreover, there was a good correlation between the in vitro dissolution and in vivo absorption of the pellets. In conclusion, CsA pellets which could ensure a constant systemic blood concentration within the therapeutic window for 24 h were prepared successfully. Meanwhile, this formulation possessed a good IVIVC.

  2. Design and In-vitro Evaluation of Sustained Release Floating Tablets of Metformin HCl Based on Effervescence and Swelling

    OpenAIRE

    Senjoti, Faria Gias; Mahmood, Syed; Jaffri, Juliana Md; Mandal, Uttam Kumar

    2016-01-01

    An oral sustained-release floating tablet formulation of metformin HCl was designed and developed. Effervescence and swelling properties were attributed on the developed tablets by sodium bicarbonate and HPMC-PEO polymer combination, respectively. Tablet composition was optimized by response surface methodology (RSM). Seventeen (17) trial formulations were analyzed according to Box-Behnken design of experiment where polymer content of HPMC and PEO at 1: 4 ratio (A), amount of sodium bi-carbon...

  3. Inventory of demonstration and trail projects in sustainable energy and transport in Scandinavia

    DEFF Research Database (Denmark)

    Andersen, Per Dannemand; Cramer-Petersen, Claus Lundgaard; Harnes, Kristian N.;

    This report documents the work of work package 2 of the InnoDemo research project funded by the Research Council of Norway. Partners in the project are The Nordic Institute for Studies in Innovation, Research and Education (NIFU) (project leader), DTU Management Engineering at Technical University...... of Denmark, and CIRCLE at Lund’s University. From a state-of-the-art study in the project’s work package 1, a set of characteristics have been specified to be collected in an inventory of demonstration projects and funding programmes. This data was collected in parallel in Denmark, Norway and Sweden...

  4. The effects of food on the bioavailability of fenofibrate administered orally in healthy volunteers via sustained-release capsule.

    Science.gov (United States)

    Yun, Hwi-Yeol; Joo Lee, Eun; Youn Chung, Soo; Choi, Sun-Ok; Kee Kim, Hyung; Kwon, Jun-Tack; Kang, Wonku; Kwon, Kwang-Il

    2006-01-01

    To examine the effects of food on plasma concentration and bioavailability of fenofibrate administered as a sustained-release capsule. Twenty-four healthy Korean volunteers were enrolled in a randomised, open-label, balanced, three-treatment, three-period, three-sequence, single oral dose, crossover pharmacokinetic study. A single dose of fenofibrate (250 mg sustained-release capsule) was administered on three occasions -- after overnight fasting, after consumption of a standard breakfast and after a high-fat breakfast. Serial blood samples were collected for the next 72 hours. Plasma fenofibric acid concentrations were measured by high-performance liquid chromatography, and pharmacokinetic parameters were calculated. The pharmacokinetic parameters were significantly affected by food intake. The high-fat breakfast affected the rate of absorption of fenofibrate more than the standard breakfast and fasted conditions. Specifically, the area under the plasma concentration-time curve from time zero to infinity (AUC(infinity)) and peak plasma concentration (C(max)) increased 2.45-fold and 2.89-fold, respectively, between the fasted and standard-fed conditions (p fenofibric acid. In healthy volunteers, AUC(infinity) and C(max) of fenofibrate, when administered via sustained-release capsules immediately after the consumption of food, was increased significantly from the fasting conditions (p < 0.01). The greatest AUC(infinity) and C(max) occurred when the capsules were taken after a high-fat breakfast.

  5. Suppression of a Field Population of Aedes aegypti in Brazil by Sustained Release of Transgenic Male Mosquitoes.

    Science.gov (United States)

    Carvalho, Danilo O; McKemey, Andrew R; Garziera, Luiza; Lacroix, Renaud; Donnelly, Christl A; Alphey, Luke; Malavasi, Aldo; Capurro, Margareth L

    2015-01-01

    The increasing burden of dengue, and the relative failure of traditional vector control programs highlight the need to develop new control methods. SIT using self-limiting genetic technology is one such promising method. A self-limiting strain of Aedes aegypti, OX513A, has already reached the stage of field evaluation. Sustained releases of OX513A Ae. aegypti males led to 80% suppression of a target wild Ae. aegypti population in the Cayman Islands in 2010. Here we describe sustained series of field releases of OX513A Ae. aegypti males in a suburb of Juazeiro, Bahia, Brazil. This study spanned over a year and reduced the local Ae. aegypti population by 95% (95% CI: 92.2%-97.5%) based on adult trap data and 81% (95% CI: 74.9-85.2%) based on ovitrap indices compared to the adjacent no-release control area. The mating competitiveness of the released males (0.031; 95% CI: 0.025-0.036) was similar to that estimated in the Cayman trials (0.059; 95% CI: 0.011-0.210), indicating that environmental and target-strain differences had little impact on the mating success of the OX513A males. We conclude that sustained release of OX513A males may be an effective and widely useful method for suppression of the key dengue vector Ae. aegypti. The observed level of suppression would likely be sufficient to prevent dengue epidemics in the locality tested and other areas with similar or lower transmission.

  6. Suppression of a Field Population of Aedes aegypti in Brazil by Sustained Release of Transgenic Male Mosquitoes.

    Directory of Open Access Journals (Sweden)

    Danilo O Carvalho

    Full Text Available The increasing burden of dengue, and the relative failure of traditional vector control programs highlight the need to develop new control methods. SIT using self-limiting genetic technology is one such promising method. A self-limiting strain of Aedes aegypti, OX513A, has already reached the stage of field evaluation. Sustained releases of OX513A Ae. aegypti males led to 80% suppression of a target wild Ae. aegypti population in the Cayman Islands in 2010. Here we describe sustained series of field releases of OX513A Ae. aegypti males in a suburb of Juazeiro, Bahia, Brazil. This study spanned over a year and reduced the local Ae. aegypti population by 95% (95% CI: 92.2%-97.5% based on adult trap data and 81% (95% CI: 74.9-85.2% based on ovitrap indices compared to the adjacent no-release control area. The mating competitiveness of the released males (0.031; 95% CI: 0.025-0.036 was similar to that estimated in the Cayman trials (0.059; 95% CI: 0.011-0.210, indicating that environmental and target-strain differences had little impact on the mating success of the OX513A males. We conclude that sustained release of OX513A males may be an effective and widely useful method for suppression of the key dengue vector Ae. aegypti. The observed level of suppression would likely be sufficient to prevent dengue epidemics in the locality tested and other areas with similar or lower transmission.

  7. Sustained release of stromal cell derived factor-1 from an antioxidant thermoresponsive hydrogel enhances dermal wound healing in diabetes.

    Science.gov (United States)

    Zhu, Yunxiao; Hoshi, Ryan; Chen, Siyu; Yi, Ji; Duan, Chongwen; Galiano, Robert D; Zhang, Hao F; Ameer, Guillermo A

    2016-09-28

    Diabetic foot ulcers (DFUs) are a severe complication of diabetes mellitus. Altered cell migration due to microcirculatory deficiencies as well as excessive and prolonged reactive oxygen species production are implicated in the delayed healing of DFUs. The goal of this research was to assess whether sustained release of SDF-1, a chemokine that promotes endothelial progenitor cell homing and angiogenesis, from a citrate-based antioxidant thermoresponsive polymer would significantly improve impaired dermal wound healing in diabetes. Poly (polyethylene glycol citrate-co-N-isopropylacrylamide) (PPCN) was synthesized via sequential polycondensation and free radical polymerization reactions. SDF-1 was entrapped via gelation of the PPCN+SDF-1 solution above its lower critical solution temperature (LCST) and its release and bioactivity was measured. The effect of sustained release of SDF-1 from PPCN (PPCN+SDF-1) versus a bolus application of SDF-1 in phosphate buffered saline (PBS) on wound healing was evaluated in a diabetic murine splinted excisional dermal wound model using gross observation, histology, immunohistochemistry, and optical coherence tomography microangiography. Increasing PPCN concentration decreased SDF-1 release rate. The time to 50% wound closure was 11days, 16days, 14days, and 17days for wounds treated with PPCN+SDF-1, SDF-1 only, PPCN only, and PBS, respectively. Wounds treated with PPCN+SDF-1 had the shortest time for complete healing (24days) and exhibited accelerated granulation tissue production, epithelial maturation, and the highest density of perfused blood vessels. In conclusion, sustained release of SDF-1 from PPCN is a promising and easy to use therapeutic strategy to improve the treatment of chronic non-healing DFUs.

  8. 黄芩苷缓释胶囊的研制%Preparation of Baicalin Sustained-Release Capsules

    Institute of Scientific and Technical Information of China (English)

    岳红坤; 王景翔; 周冉; 关倩

    2012-01-01

    The prescription is optimized through evaluating the release in vitro to prepare sustained-release baicalin capsules. With baicalin for apis, hydroxyl armour cellulose (HPMC), microcrystalline cellulose (MCC), lactose, PVP ethanol solution concentration to prepare the sustained-release capsules,influence on each different factor is investigated. Using the rthogonal test method,the optimization of prescription is completed. The optimized baicalin sustained-release capsule prescription is presented : HPMC 0.25 g,baicalin 0.5 g, MCC 0.2 g, PVP ethanol solution concentration 6% ,lactose 0.25 g. This research method is simple and rapid ;the in-vitro release of baicalin also shows good rationality of the prescription design, and it can be further developed.%制备黄芩苷缓释胶囊,并通过体外释放度对其处方进行优化.以黄芩苷为原料药,羟丙甲纤维素(HPMC)、微晶纤维素(MCC)、乳糖、聚维酮(PVP)的乙醇溶液为辅料制备缓释胶囊,考察不同因素对释放度的影响,通过正交试验优化制备处方.优化后的黄芩苷缓释胶囊的处方为黄芩苷0.5 g,HPMC 0.25 g,MCC 0.2 g,PVP的乙醇溶液浓度为6%,乳糖0.25 g.研究方法简便、快速,体外释放度显示黄芩苷缓释胶囊处方设计比较合理,可进一步研发.

  9. Suppression of a Field Population of Aedes aegypti in Brazil by Sustained Release of Transgenic Male Mosquitoes.

    Directory of Open Access Journals (Sweden)

    Danilo O Carvalho

    Full Text Available The increasing burden of dengue, and the relative failure of traditional vector control programs highlight the need to develop new control methods. SIT using self-limiting genetic technology is one such promising method. A self-limiting strain of Aedes aegypti, OX513A, has already reached the stage of field evaluation. Sustained releases of OX513A Ae. aegypti males led to 80% suppression of a target wild Ae. aegypti population in the Cayman Islands in 2010. Here we describe sustained series of field releases of OX513A Ae. aegypti males in a suburb of Juazeiro, Bahia, Brazil. This study spanned over a year and reduced the local Ae. aegypti population by 95% (95% CI: 92.2%-97.5% based on adult trap data and 81% (95% CI: 74.9-85.2% based on ovitrap indices compared to the adjacent no-release control area. The mating competitiveness of the released males (0.031; 95% CI: 0.025-0.036 was similar to that estimated in the Cayman trials (0.059; 95% CI: 0.011-0.210, indicating that environmental and target-strain differences had little impact on the mating success of the OX513A males. We conclude that sustained release of OX513A males may be an effective and widely useful method for suppression of the key dengue vector Ae. aegypti. The observed level of suppression would likely be sufficient to prevent dengue epidemics in the locality tested and other areas with similar or lower transmission.

  10. Suppression of a Field Population of Aedes aegypti in Brazil by Sustained Release of Transgenic Male Mosquitoes

    Science.gov (United States)

    Garziera, Luiza; Lacroix, Renaud; Donnelly, Christl A.; Alphey, Luke; Malavasi, Aldo; Capurro, Margareth L.

    2015-01-01

    The increasing burden of dengue, and the relative failure of traditional vector control programs highlight the need to develop new control methods. SIT using self-limiting genetic technology is one such promising method. A self-limiting strain of Aedes aegypti, OX513A, has already reached the stage of field evaluation. Sustained releases of OX513A Ae. aegypti males led to 80% suppression of a target wild Ae. aegypti population in the Cayman Islands in 2010. Here we describe sustained series of field releases of OX513A Ae. aegypti males in a suburb of Juazeiro, Bahia, Brazil. This study spanned over a year and reduced the local Ae. aegypti population by 95% (95% CI: 92.2%-97.5%) based on adult trap data and 81% (95% CI: 74.9-85.2%) based on ovitrap indices compared to the adjacent no-release control area. The mating competitiveness of the released males (0.031; 95% CI: 0.025-0.036) was similar to that estimated in the Cayman trials (0.059; 95% CI: 0.011 – 0.210), indicating that environmental and target-strain differences had little impact on the mating success of the OX513A males. We conclude that sustained release of OX513A males may be an effective and widely useful method for suppression of the key dengue vector Ae. aegypti. The observed level of suppression would likely be sufficient to prevent dengue epidemics in the locality tested and other areas with similar or lower transmission. PMID:26135160

  11. Effect of rhBMP-2 sustained-release nanocapsules on the ectopic osteogenesis process in Sprague-Dawley rats

    Institute of Scientific and Technical Information of China (English)

    Ren-Fa Lai; Ze-Jian Li; Zhi-Ying Zhou; Zhi-Qiang Feng; Qing-Tong Zhao

    2013-01-01

    Objective:To explore the effect of sustained-release recombinant human bone morphogenetic protein-2(rhBMP-2) on ectopic osteogenesis in the muscle pouches of rats through preparing rhBMP-2 sustained-release capsules by wrapping morphogenesis protein bones-2(BMP-2) using chitosan nanoparticles, and compositing collagen materials.Methods:Twenty fourSprague-Dawley rats were randomly divided into four groups with six rats in each group, that isGroupA (control group),GroupB(only treated with collagen),GroupC(rhBMP-2+collagen treated group) andGroupD(rhBMP-2/cs+collagen treated group).The composite materials for each group were implanted in the bilateral peroneal muscle pouches in rats.The peroneal muscles were only separated without implanting any materials in control group.Rats were sacrificed2 weeks and4 weeks post treatment and samples were cut off for general observation,MicroCT scans and histological observation.Results:General observation showed no new bone formation in GroupsA andB mice, while new bones were formed inGroupsC andD mice.Two weeks after treatmentMicroCT scans showed thatThe bone volume fraction(BVF), trabecular thickness(Tb. Th), bone mineral density(BMD) inGroupC mice were all higher than that inGroupD(P<0.05). At the fourth week, theBVF,Tb.Th andBMD were significantly higher than that at the second week(P<0.01).Conclusions:The slow-release effect of rhBMP-2/cs sustained-release capsules can significantly promote ectopic osteogenesis.Its bone formation effect is better than that of rhBMP-2 burst-release group.

  12. Public demonstration projects and field trials: Accelerating commercialisation of sustainable technology in solar photovoltaics

    Energy Technology Data Exchange (ETDEWEB)

    Brown, James [Cass Business School, City University, 106 Bunhill Row, London EC1Y 8TZ (United Kingdom)], E-mail: j.e.brown@city.ac.uk; Hendry, Chris [Cass Business School, City University, 106 Bunhill Row, London EC1Y 8TZ (United Kingdom)], E-mail: c.n.hendry@city.ac.uk

    2009-07-15

    The paper considers the role of government funded demonstration projects and field trials (DTs) in accelerating the commercialisation of new energy technologies that meet a public good but do not have immediate market appeal [Sagar, A.D., van der Zwaan, B., 2006. Technological innovation in the energy sector: R and D, deployment, and learning-by-doing. Energy Policy 34, 2601-2608]. Drawing on an original database of DTs in the EU, Japan and USA from 1973 to 2004, we review the history of DTs in photovoltaic technology for electricity generation, and its subsequent take up as a commercial energy source. We find that DTs that are aimed purely at discovering suitable market opportunities are less successful in achieving diffusion than projects that target a particular application and concentrate resources on it. The former nevertheless have a vital role to play in the learning process, while a targeted focus is often dependent on national industrial and institutional factors.

  13. Public demonstration projects and field trials. Accelerating commercialisation of sustainable technology in solar photovoltaics

    Energy Technology Data Exchange (ETDEWEB)

    Brown, James; Hendry, Chris [Cass Business School, City University, 106 Bunhill Row, London EC1Y 8TZ (United Kingdom)

    2009-07-15

    The paper considers the role of government funded demonstration projects and field trials (DTs) in accelerating the commercialisation of new energy technologies that meet a public good but do not have immediate market appeal [Sagar, A.D., van der Zwaan, B., 2006. Technological innovation in the energy sector: R and D, deployment, and learning-by-doing. Energy Policy 34, 2601-2608]. Drawing on an original database of DTs in the EU, Japan and USA from 1973 to 2004, we review the history of DTs in photovoltaic technology for electricity generation, and its subsequent take up as a commercial energy source. We find that DTs that are aimed purely at discovering suitable market opportunities are less successful in achieving diffusion than projects that target a particular application and concentrate resources on it. The former nevertheless have a vital role to play in the learning process, while a targeted focus is often dependent on national industrial and institutional factors. (author)

  14. Plan for Demonstration of Online Monitoring for the Light Water Reactor Sustainability Online Monitoring Project

    Energy Technology Data Exchange (ETDEWEB)

    Magdy S. Tawfik; Vivek Agarwal; Nancy J. Lybeck

    2011-09-01

    Condition based online monitoring technologies and development of diagnostic and prognostic methodologies have drawn tremendous interest in the nuclear industry. It has become important to identify and resolve problems with structures, systems, and components (SSCs) to ensure plant safety, efficiency, and immunity to accidents in the aging fleet of reactors. The Machine Condition Monitoring (MCM) test bed at INL will be used to demonstrate the effectiveness to advancement in online monitoring, sensors, diagnostic and prognostic technologies on a pilot-scale plant that mimics the hydraulics of a nuclear plant. As part of this research project, INL will research available prognostics architectures and their suitability for deployment in a nuclear power plant. In addition, INL will provide recommendation to improve the existing diagnostic and prognostic architectures based on the experimental analysis performed on the MCM test bed.

  15. Antioxidant effect of immediate- versus sustained-release melatonin in type 2 diabetes mellitus and healthy controls.

    Science.gov (United States)

    Rybka, Joanna; Kędziora-Kornatowska, Kornelia; Kupczyk, Daria; Muszalik, Marta; Kornatowski, Maciej; Kędziora, Józef

    2016-01-01

    Oxidative damage has been suggested as the primary cause of aging and age-associated diseases including type 2-dependent diabetes mellitus (T2DM) and therefore there is a growing interest in exploring therapeutic potential of antioxidant agents including melatonin. In the present study, we analyzed red blood cell antioxidants and lipid peroxidation after 5 mg/daily immediate-release melatonin treatment of elderly T2DM patients and healthy elderly subjects in comparison with 2 mg/daily sustained-release melatonin treatment of elderly T2DM patients and healthy elderly subjects, to determine the antioxidant effect of different doses and formulations of melatonin in these groups. Our study revealed that there was no significant difference in antioxidant status of red blood cells measured by glutathione concentration and activities of GPx-1, CAT, GR, SOD-1 and MDA levels, after supplementation with 2 mg-sustained release melatonin or with 5 mg-immediate release melatonin, either in T2DM or in healthy elderly subjects. These results suggest that both preparations may exert similar therapeutic effect related to melatonin's action on antioxidant defense system.

  16. Sustained Release of Diltiazem Hydrochloride from Cross-linked Biodegradable IPN Hydrogel Beads of Pectin and Modified Xanthan Gum.

    Science.gov (United States)

    Giri, T K; Choudhary, C; Alexander, A; Ajazuddin; Badwaik, H; Tripathy, M; Tripathi, D K

    2013-11-01

    Interpenetrating polymer network hydrogel beads of pectin and sodium carboxymethyl xanthan were prepared by ionotropic gelation with Al(+3) ions and covalent cross-linking with glutaraldehyde for sustained delivery of diltiazem hydrochloride. Fourier transform infrared spectroscopy, X-ray diffraction, differential scanning colorimetry and scanning electron microscopy were used to characterise the hydrogel beads. The swelling of the hydrogel and the release of drug were relatively low in pH 1.2 buffer solutions. However, higher swelling and drug release were observed in pH 6.8 buffer solutions. The carboxyl functional groups of hydrogels undergo ionisation and the osmotic pressure inside the beads increases resulting in higher swelling and drug release in higher pH. The release of drug depends on concentration of polymer, amount and exposure time of cross-linker and drug content in the hydrogel matrices. The present study indicated that the hydrogel beads minimised the drug release in pH 1.2 buffer solutions and to prolong the drug release in pH 6.8 buffer solutions.

  17. Sustained release of diltiazem hydrochloride from cross-linked biodegradable IPN hydrogel beads of pectin and modified xanthan gum

    Directory of Open Access Journals (Sweden)

    T K Giri

    2013-01-01

    Full Text Available Interpenetrating polymer network hydrogel beads of pectin and sodium carboxymethyl xanthan were prepared by ionotropic gelation with Al +3 ions and covalent cross-linking with glutaraldehyde for sustained delivery of diltiazem hydrochloride. Fourier transform infrared spectroscopy, X-ray diffraction, differential scanning colorimetry and scanning electron microscopy were used to characterise the hydrogel beads. The swelling of the hydrogel and the release of drug were relatively low in pH 1.2 buffer solutions. However, higher swelling and drug release were observed in pH 6.8 buffer solutions. The carboxyl functional groups of hydrogels undergo ionisation and the osmotic pressure inside the beads increases resulting in higher swelling and drug release in higher pH. The release of drug depends on concentration of polymer, amount and exposure time of cross-linker and drug content in the hydrogel matrices. The present study indicated that the hydrogel beads minimised the drug release in pH 1.2 buffer solutions and to prolong the drug release in pH 6.8 buffer solutions.

  18. Preparation and In-Vitro Evaluation of Sustained Release Matrix Diclofenac Sodium Tablets Using HPMC KM 100 and Gums

    Directory of Open Access Journals (Sweden)

    Zafar Iqbal, Raza Khan, Fazli Nasir, Jamshaid Ali Khan, Lateef Ahmad, Abad Khan, Yaser Shah

    2010-12-01

    Full Text Available Objectives: The impact of hydroxypropylmethyl cellulose(HPMC K 100M alone and in combination with the guar gum,xanthan gum and gum tragacanth on the release of the diclofenac sodium matrix tablets were evaluated.Materials and Methods: The granules were prepared using wet granulation method and compressed into tablets using different ratio of drug and gum ratio. The physical properties of the tablets were within acceptable pharmacopeial limits.The release profiles of the matrix tablets were evaluated in vitro,using USP dissolution apparatus II (paddle method.Results: The formulations containing HPMC K 100M drug ratio1:1.3 and 1:1.6 and formulations containing HPMC, gum and drug with different ratio also sustained the release of diclofenac sodium for 12 hours. The mechanism of drug release from the matrix tablets was studied using Zero order, First order, Higuchi and Korsmeyer’s models using regression coefficient method. The stability of the selected formulations was evaluated at 40˚C and 70% RH for 6 months.Conclusions: HPMC K100M alone and in combination with natural gums as the retarding material retarded the release upto 12 hours and showed little deviation from the theoretical release pattern.

  19. 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.

  20. Supraphysiological cyclic dosing of sustained release T3 in order to reset low basal body temperature.

    Science.gov (United States)

    Friedman, Michael; Miranda-Massari, Jorge R; Gonzalez, Michael J

    2006-03-01

    The use of sustained release tri-iodothyronine (SR-T3) in clinical practice, has gained popularity in the complementary and alternative medical community in the treatment of chronic fatigue with a protocol (WT3) pioneered by Dr. Denis Wilson. The WT3 protocol involves the use of SR-T3 taken orally by the patient every 12 hours according to a cyclic dose schedule determined by patient response. The patient is then weaned once a body temperature of 98.6 degrees F has been maintained for 3 consecutive weeks. The symptoms associated with this protocol have been given the name Wilson's Temperature Syndrome (WTS). There have been clinical studies using T3 in patients who are euthyroid based on normal TSH values. However, this treatment has created a controversy in the conventional medical community, especially with the American Thyroid Association, because it is not based on a measured deficiency of thyroid hormone. However, just as estrogen and progesterone are prescribed to regulate menstrual cycles in patients who have normal serum hormone levels, the WT3 therapy can be used to regulate metabolism despite normal serum thyroid hormone levels. SR-T3 prescription is based exclusively on low body temperature and presentation of symptoms. Decreased T3 function exerts widespread effects throughout the body. It can decrease serotonin and growth hormone levels and increase the number of adrenal hormone receptor sites. These effects may explain some of the symptoms observed in WTS. The dysregulation of neuroendocrine function may begin to explain such symptoms as alpha intrusion into slow wave sleep, decrease in blood flow to the brain, alterations in carbohydrate metabolism, fatigue, myalgia and arthralgia, depression and cognitive dysfunction. Despite all thermoregulatory control mechanisms of the body and the complex metabolic processes involved, WT3 therapy seems a valuable tool to re-establish normal body functions. We report the results of 11 patients who underwent the

  1. Effect of Misoprostol on the Pharmacokinetics of Sustained Release Diclofenac in Myanmar Healthy Male Volunteers

    Directory of Open Access Journals (Sweden)

    Htet Htet Aung

    2017-03-01

    Full Text Available Background: Sustained release diclofenac (diclofenac SR is the commonly used non-steroidal anti-inflammatory drug for chronic inflammatory conditions such as rheumatoid arthritis. Misoprostol, prostaglandin analogue, is the agent that enhances gastrointestinal mucosal defense. Concomitant administration of misoprostol with diclofenac SR can prevent the gastrointestinal side effects of diclofenac SR. Objective: The purpose of the study was to explore the effect of misoprostol on the pharmacokinetics of diclofenac SR in healthy volunteers. Methods: Crossover study was evaluated in 14 male volunteers. Single oral dose of 100 mg diclofenac SR was concomitantly administered with 200 μg misoprostol with one-week wash out period. Plasma concentrations at 0, 0.5, 1, 1.5, 2, 3, 6 and 10 hrs were determined by high performance liquid chromatography (HPLC. Pharmacokinetic parameters such as area under concentration-time curve (AUC0-α, peak plasma concentration (Cmax, time to achieve peak plasma concentration (Tmax, absorption half-life (T½(ab, elimination half-life (T1/2(el, absorption rate constant (Kab, and elimination rate constant (Kel were determined. Results: With misoprostol, the mean AUC0-α of diclofenac SR was significantly reduced from 12.11±5.25μg/ mL×hr to 4.17±2.72μg/mL×hr (p0.05. The mean T½(ab was decreased from 0.56±0.23hr to 0.54±0.19hr (p>0.05. The mean Kab were almost the same 1.43±0.54hr-1 and 1.43±0.48hr-1. The mean T1/2(el was decreased from 3.68±1.64hr to 3.03±1.08hr (p>0.05. The mean Kel was increased from 0.21±0.09hr-1 to 0.25±0.09hr-1 (p>0.05. Conclusion: There was a significant reduction in the extent of absorption of diclofenac SR when concomitantly administered with misoprostol. Therefore, the dose of diclofenac SR may need to be increased to avoid therapeutic failure of diclofenac SR or concurrent use with misoprostol may need to be changed to other gastroprotective agents.

  2. Preparation and evaluation of biodegradable microspheres containing a new potent osteogenic compound and new synthetic polymers for sustained release.

    Science.gov (United States)

    Umeki, Nobuo; Sato, Takayuki; Harada, Masahiro; Takeda, Junko; Saito, Shuji; Iwao, Yasunori; Itai, Shigeru

    2010-06-15

    In order to achieve the sustained release of 3-ethyl-4-(4-methylisoxazol-5-yl)-5-(methylthio) thiophene-2-carboxamide (BFB0261), a new potent osteogenic compound for the treatment of bone disorders, we prepared microspheres containing BFB0261 and newly synthesized three poly (D, L-lactic acid) (PLA), four poly (D, L-lactic acid-co-glycolic acid) (PLGA), and eight poly (D, L-lactic acid)-block-poly(ethylene glycol) (PLA-PEG) biodegradable polymers or copolymers, and evaluated the release pattern of BFB0261 from the microspheres in vitro and in vivo. The mean particle size of the microspheres, except for the microspheres constructed from PLA-PEG with a greater than 20% PEG component, was in the range of approximately 10-50 microm, and the preparations showed a spherical shape with a smooth surface. In an in vitro release study, the release of BFB0261 from PLA-1 (Mw: 36 kDa), PLAPEG9604H (PLA/PEG ratio: 96:4, Mw: 181 kDa), or PLAPEG8317 (PLA/PEG ratio: 83:17, Mw: 106 kDa) microspheres occurred in a zero-order manner with a slow release, and more than 50% of BFB0261 remained in each type of microsphere at 12 weeks after incubation. When the BFB0261 microspheres constructed from various polymers were intramuscularly administered to the rat femur, the microspheres constructed from PLA-1 or PLAPEG9604H were able to achieve a sustained release of BFB0261 at the injection site for 6 weeks. The present information indicates that microspheres constructed from PLA-1 or PLAPEG9604H may be feasible for bone engineering. Copyright 2010 Elsevier B.V. All rights reserved.

  3. Formulation and the in-vitro and biopharmaceutical evaluation of sustained release tablet of verapamil HCL using precirol ATO 5 through melt granulation technique

    Directory of Open Access Journals (Sweden)

    Bhagwat Durgacharan

    2009-01-01

    Full Text Available Sustained release tablet of Verapamil hydrochloride (VPH was prepared by using Precirol ATO 5 (PREC by direct compression of matrices prepared by using the melt granulation technique. The effect of different concentrations of PREC on the in-vitro drug release of VPH was studied by comparing it with the marketed formulation and percent release given in USP for VPH extended release tablets. Effect of release enhancers such as microcrystalline cellulose (MCC and lactose on in-vitro drug release was also studied. Biopharmaceutical evaluation of the satisfactory formulation was also performed in order to estimate the maximum concentration of drug in plasma (C max , time required to reach maximum concentration (t max , elimination rate constant (k, elimination rate constant (t 1/2 , area under curve (AUC (0-t and AUC (02a, apparent volume of distribution (V d and mean residence time. The results showed that PREC can be utilized as the matrix forming agent to sustain the release of VPH. The results of biopharmaceutical evaluation showed that the rate of absorption appeared to be more sustained, resulting in a more uniform plasma concentration profile of VPH. More bioavailability was noted with the sustained release formulation even though the drug has substantial first pass metabolism. The results indicated that it is possible to make once-a-day sustained-release tablet of VPH by using the melt granulation technique.

  4. DEMONSTRATION OF LEACHXS/ORCHESTRA CAPABILITIES BY SIMULATING CONSTITUENT RELEASE FROM A CEMENTITIOUS WASTE FORM IN A REINFORCED CONCRETE VAULT

    Energy Technology Data Exchange (ETDEWEB)

    Langton, C.; Meeussen, J.; Sloot, H.

    2010-03-31

    The objective of the work described in this report is to demonstrate the capabilities of the current version of LeachXS{trademark}/ORCHESTRA for simulating chemical behavior and constituent release processes in a range of applications that are relevant to the CBP. This report illustrates the use of LeachXS{trademark}/ORCHESTRA for the following applications: (1) Comparing model and experimental results for leaching tests for a range of cementitious materials including cement mortars, grout, stabilized waste, and concrete. The leaching test data includes liquid-solid partitioning as a function of pH and release rates based on laboratory column, monolith, and field testing. (2) Modeling chemical speciation of constituents in cementitious materials, including liquid-solid partitioning and release rates. (3) Evaluating uncertainty in model predictions based on uncertainty in underlying composition, thermodynamic, and transport characteristics. (4) Generating predominance diagrams to evaluate predicted chemical changes as a result of material aging using the example of exposure to atmospheric conditions. (5) Modeling coupled geochemical speciation and diffusion in a three layer system consisting of a layer of Saltstone, a concrete barrier, and a layer of soil in contact with air. The simulations show developing concentration fronts over a time period of 1000 years. (6) Modeling sulfate attack and cracking due to ettringite formation. A detailed example for this case is provided in a separate article by the authors (Sarkar et al. 2010). Finally, based on the computed results, the sensitive input parameters for this type of modeling are identified and discussed. The chemical speciation behavior of substances is calculated for a batch system and also in combination with transport and within a three layer system. This includes release from a barrier to the surrounding soil as a function of time. As input for the simulations, the physical and chemical properties of the

  5. Improvement in autologous human fat transplant survival with SVF plus VEGF-PLA nano-sustained release microspheres.

    Science.gov (United States)

    Li, Liqun; Pan, Shengsheng; Ni, Binting; Lin, Yuanshao

    2014-08-01

    Early neovascularization is important for autologous fat transplant survival. SVF cells are ideal seed cells. Both vascular endothelial growth factor (VEGF) and SVF cells can promote neovascularization. However, the half-life (about 50 min) of VEGF is too short to sustain an adequate local concentration. We have investigated whether VEGF-polylactic acid (PLA) nano-sustained release microspheres plus SVF cells can improve neovascularization and survival of transplanted fat tissues. SVF cells were harvested and constructed VEGF-PLA nano-sustained release microspheres in vitro. Human fat tissues was mixed with SVF cells plus VEGF-PLA, SVF cells alone or Dulbecco's modified Eagle's medium as the control. These three mixtures were injected into random sites in 18 nude mice. Two months later, the transplants were weighed and examined histologically; and capillaries were counted to quantify neovascularization. Hematoxylin-eosin (HE) and anti-VEGF stains were applied to reveal cell infiltration. The mean wet weight of fat in the SVF plus VEGF-PLA, SVF alone, and control transplants were 0.18 ± 0.013 g, 0.16 ± 0.015 g, and 0.071 ± 0.12 g, respectively; the differences between groups were statistically significant. More vessels were present in the SVF plus VEGF-PLA transplants than in the other two types. Transplants mixed with SVF cells also had an acceptable density of capillaries. Histological analysis revealed that both the SVF plus VEGF-PLA and SVF alone transplants, but not the control transplants, were composed of adipose tissue, and had less fat necrosis and less fibrosis than control specimens. SVF plus VEGF-PLA transplants had significantly greater capillary density and VEGF expression than the other two transplant groups. Thus transplanted fat tissue survival and quality can be enhanced by the addition of VEGF-PLA nano-sustained release microspheres plus SVF cells.

  6. Dealing way of release medium in ibuprofen sustained-release capsules%布洛芬缓释胶囊释放介质处理方式研究

    Institute of Scientific and Technical Information of China (English)

    邵超; 沈黎

    2011-01-01

    目的 考察释放介质处理方式对布洛芬缓释胶囊释放度的影响.方法 对不同生产企业的三批布洛芬缓释胶囊,考察了煮沸、超声、减压抽滤三种不同脱气方式对释放度的影响;对煮沸法配制释放介质,考察了放置时间对释放度的影响.结果 释放介质脱气方式和放置时间,对布洛芬缓释胶囊释放度有较大影响.结论 布洛芬缓释胶囊释放度检查,释放介质应使用煮沸法脱气,快速降温.%Aim To explore the influence of the way dealing with release medium upon the releasing degree of ibuprofen sustained-release capsules. Methods Through examining three bacthes of ibuprofen sustained-release capsules from different pharmaceutical companies,and the influence upon the releasing degree was observed by three different degassing ways - boiling,ultrasound and vacuum filtration,to explore the influence of standing time upon the releasing degree in release medium made by boiling way. Results The degassing ways and standing time of release medium had great influence upon the releasing degree of release medium in ibuprofen sustained-release capsules. Conclusion Testing on the releasing degree of release medium in ibuprofen sustained-release capsules proves that release medium should be degassed by boiling way,in order to be cooled down rapidly.

  7. 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.

  8. Aqueous coating dispersion (pseudolatex) of zein improves formulation of sustained-release tablets containing very water-soluble drug.

    Science.gov (United States)

    Li, X N; Guo, H X; Heinamaki, J

    2010-05-01

    Zein is an alcohol soluble protein of corn origin that exhibits hydrophobic properties. Pseudolatexes are colloidal dispersions containing spherical solid or semisolid particles less than 1 microm in diameter and can be prepared from any existing thermoplastic water-insoluble polymer. The novel plasticized film-coating pseudolatex of zein was studied in formulation of sustained-release tablets containing very water-soluble drug. Film formation of plasticized aqueous dispersion was compared with film forming properties of plasticized organic solvent system (ethanol) of zein. The water vapor permeability (WVP), water uptake and erosion, and moisture sorption were evaluated with free films. The tablets containing metoprolol tartrate as a model drug were used in pan-coating experiments. Aqueous film coatings plasticized with PEG 400 exhibited very low water uptake. No significant difference in WVP, moisture sorption and erosion were found between aqueous films and organic solvent-based films of zein plasticized with PEG 400. The atomic force microscopy (AFM) images on microstructure of films showed that colloidal particle size of zein in the aqueous films was smaller than that observed in the solvent-based films. In addition, the aqueous-based films were more compact and smoother than the respective solvent-based films. The aqueous zein-coated tablets containing very water-soluble drug (metoprolol tartrate) exhibited clear sustained-release dissolution profiles in vitro, while the respective solvent-based film-coated tablets showed much faster drug release. Furthermore, aqueous zein-coated tablets had lower water absorption at high humidity conditions. In conclusion, the plasticized aqueous dispersion (pseudolatex) of zein can be used for moisture resistant film coating of sustained-release tablets containing very water-soluble drug.

  9. 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

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

    Science.gov (United States)

    Franca, Juçara Ribeiro; Foureaux, Giselle; Fuscaldi, Leonardo Lima; Ribeiro, Tatiana Gomes; Rodrigues, Lívia Bomfim; Bravo, Renata; Castilho, Rachel Oliveira; Yoshida, Maria Irene; Cardoso, Valbert Nascimento; Fernandes, Simone Odília; Cronemberger, Sebastião; Ferreira, Anderson José; Faraco, André Augusto Gomes

    2014-01-01

    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 promising system

  11. Formulation and evaluation of hydroxyzine hydrochloride sustained release microspheres by ionotropic gelation technique using Carbopol 934P

    Directory of Open Access Journals (Sweden)

    Soumyadeep Ghosh

    2014-01-01

    Full Text Available Preparation of sustained release microspheres of hydroxyzine hydrochloride by ionotropic gelation technique and evaluation. Microspheres of hydroxyzine hydrochloride were prepared by ionotropic gelation method using sodium alginate, Carbopol 934P and calcium chloride. The powders were evaluated for their flow properties. Hydroxyzine hydrochloride microspheres were characterized by Fourier transform infrared and in vitro dissolution studies. The drug release study of hydroxyzine hydrochloride microspheres was evaluated using basket type dissolution test apparatus. The release rate of Hydroxyzine hydrochloride microspheres was studied for 12 h in pH 7.4 phosphate buffer media. From the five batches F5 batch showed good release behavior 91.08% of drug is released over 12 h, and r2 = 0.987 in zero-order kinetics. The microspheres were prepared without the use of organic solvents. Microspheres of hydroxyzine hydrochloride decrease the incidence of side effects and also improve patient compliance by reducing the number of dosing and by reducing the fluctuations of drug in the blood. This entire attributed attitude proves that microsphere technology from novel drug delivery can be very much effective in reducing dosage frequency, dose dumping, and better patient compliance and economical to the patient. In the future, natural, biodegradable polymers can be used to improve therapeutic efficacy of the drug and further minimizing side-effects.

  12. In vitro release of 1,3-bis (2-chloroethyl)-1-nitrosourea sustained-release microspheres and the distribution in rat brain tissues

    Institute of Scientific and Technical Information of China (English)

    Xia Li; Liping Guo; Qin Li

    2006-01-01

    BACKGROUND: The implantation of released chemotherapeutic drugs, which takes biodegradable polymer as vector, into the tumor site can get high concentration and release the drug for a long time, it can directly act on the tumor cells, and reduce the general toxicity.OBJECTIVE: To explore the in vitro and in vivo course of 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU) sustained-release from BCNU-loaded polylactide (PLA) microspheres (MS) and location in rat brain tissue.DESIGN: A repetitive measurement.SETTING: Central Pharmacy, General Hospital of Chinese People's Armed Police Forces.MATERIALS: Thirty male SD rats were used. PLA (Mr5000, batch number: KSL8377) was produced by Wako Pure Chemical Inc.,Ltd. (Japan); BCNU (batch number: 021121) by Tianjin Jinyao Amino Acid Co., Ltd.;BCNU-PLA-MS was prepared by the method of solvent evaporation and pressed into tablets (10 mg/tablet).High-performance liquid chromatography (HPLC) Agilent 1100 (USA); LS9800 liquid-scintillation radiometric apparatus (Beckman). Chromatographic conditions: Elite Hypersil ODS2 C18 chromatographic column (5 μm,4.6 mm ×150 mm); Mobile phase: methanol: water (50:50), flow rate was 1.0 mL per minute, wave length of ultraviolet detection was 237 nm, and the inlet amount of samples was 10 μL.METHODS: The experiments were carried out in the experimental animal center of the General Hospital of Chinese Armed Police from May 2004 to July 2005. ① In vitro BCNU-PLA-MS release test: BCNU-PLA-MS was prepared by the method of solvent evaporation, then placed in 0.1 mol/L phosphate buffered solution (PBS, pH 7.4, 37 ℃), part of MS were taken out at 1, 2, 3, 7, 10 and 15 days respectively, and the rest amount of BCNU in MS was determined by HPLC, then the curve of BCNU-PLA-MS release was drawn. ②In vivo BCNU-PLA-MS release and distribution test: The rats were anesthetized, then BCNU-PLA-MS were implanted to the site 1 mm inferior to the cortex of frontal lobe. Five rats were killed postoperatively

  13. Bone regenerating effect of surface-functionalized titanium implants with sustained-release characteristics of strontium in ovariectomized rats

    Science.gov (United States)

    Offermanns, Vincent; Andersen, Ole Zoffmann; Riede, Gregor; Andersen, Inge Hald; Almtoft, Klaus Pagh; Sørensen, Søren; Sillassen, Michael; Jeppesen, Christian Sloth; Rasse, Michael; Foss, Morten; Kloss, Frank

    2016-01-01

    Since strontium (Sr) is known for its anabolic and anticatabolic effect on bone, research has been focused on its potential impact on osseointegration. The objective of this study was to investigate the performance of nanotopographic implants with a Sr-functionalized titanium (Ti) coating (Ti–Sr–O) with respect to osseointegration in osteoporotic bone. The trial was designed to examine the effect of sustained-release characteristics of Sr in poor-quality bone. Three Ti–Sr–O groups, which differed from each other in coating thickness, Sr contents, and Sr release, were examined. These were prepared by a magnetron sputtering process and compared to uncoated grade 4 Ti. Composition, morphology, and mechanical stability of the coatings were analyzed, and Sr release data were gained from in vitro washout experiments. In vivo investigation was carried out in an osteoporotic rat model and analyzed histologically, 6 weeks and 12 weeks after implantation. Median values of bone-to-implant contact and new bone formation after 6 weeks were found to be 84.7% and 54.9% (best performing Sr group) as compared to 65.2% and 23.8% (grade 4 Ti reference), respectively. The 12-week observation period revealed 84.3% and 56.5% (best performing Sr group) and 81.3% and 39.4% (grade 4 Ti reference), respectively, for the same measurements. The increase in new bone formation was found to correlate with the amount of Sr released in vitro. The results indicate that sputtered nanostructured Ti–Sr–O coatings showed sustained release of Sr and accelerate osseointegration even in poor-quality bone, and thus, may have impact on practical applications for medical implants. PMID:27313456

  14. 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.

  15. ENHANCED LIVER DELIVERY AND SUSTAINED RELEASE OF CURCUMIN WITH DRUG LOADED NANOPARTICLES AFTER INTRAVENOUS ADMINISTRATION IN RATS

    Directory of Open Access Journals (Sweden)

    SURESH K, BONEPALLY REDDY, JITHAN A

    2013-09-01

    Full Text Available Liver targeting drug delivery systems can improve thedelivery of several drugs useful in the treatment of liverdisorders such as cirrhosis and liver cancer. Theobjective of this study was to prepare the biodegradablenanoparticles containing curcumin, a well-knownhepatoprotective agent and further to evaluate the livertargetability and sustained release of curcumin with thedeveloped nanoformulation. Curcumin nanoparticleswere prepared by double emulsion (w/o/w solventevaporation method using different drug polymer ratios.Poly-ε-caprolactone was used in the preparation. Theprepared formulations were evaluated for particles size,surface potential, entrapment efficiency, in vitro release,drug polymer interaction. Four different formulationsCNP1, CNP2, CNP3 and CNP4 were prepared.Optimized formulation (CNP3 was evaluated forpharmacokinetics and hepatoprotective activity in CCl4induced liver toxicity model after i.v. administration.Optimized formulation was selected based on the size,entrapment efficiency and release characteristics.Curcumin i.v. solution and oral suspension form wereused as the reference. Particle size of all formulationswas in the range of 300-470 nm and the entrapmentefficiencies were in the range of 75-85 %. Drug releasefrom the nanoparticles was sustained both in vitro and invivo. Nanoparticle formulation tested in vivodemonstrated better pharmacokinetics andpharmacodynamics compared to the reference. Druglevels in the liver were significantly higher withnanoparticular formulation. Thus, this studysuccessfully prepared a nanoparticular formulationcontaining curcumin with polycaprolactone as thepolymer. With the developed formulation better livertargetability was achieved.

  16. 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.

  17. 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%).

  18. Autologous adipose tissue-derived stem cells treatment demonstrated favorable and sustainable therapeutic effect for Crohn's fistula.

    Science.gov (United States)

    Lee, Woo Yong; Park, Kyu Joo; Cho, Yong Beom; Yoon, Sang Nam; Song, Kee Ho; Kim, Do Sun; Jung, Sang Hun; Kim, Mihyung; Yoo, Hee-Won; Kim, Inok; Ha, Hunjoo; Yu, Chang Sik

    2013-11-01

    Fistula is a representative devastating complication in Crohn's patients due to refractory to conventional therapy and high recurrence. In our phase I clinical trial, adipose tissue-derived stem cells (ASCs) demonstrated their safety and therapeutic potential for healing fistulae associated with Crohn's disease. This study was carried out to evaluate the efficacy and safety of ASCs in patients with Crohn's fistulae. In this phase II study, forty-three patients were treated with ASCs. The amount of ASCs was proportioned to fistula size and fistula tract was filled with ASCs in combination with fibrin glue after intralesional injection of ASCs. Patients without complete closure of fistula at 8 weeks received a second injection of ASCs containing 1.5 times more cells than the first injection. Fistula healing at week 8 after final dose injection and its sustainability for 1-year were evaluated. Healing was defined as a complete closure of external opening without any sign of drainage and inflammation. A modified per-protocol analysis showed that complete fistula healing was observed in 27/33 patients (82%) by 8 weeks after ASC injection. Of 27 patients with fistula healing, 26 patients completed additional observation study for 1-year and 23 patients (88%) sustained complete closure. There were no adverse events related to ASC administration. ASC treatment for patients with Crohn's fistulae was well tolerated, with a favorable therapeutic outcome. Furthermore, complete closure was well sustained. These results strongly suggest that autologous ASC could be a novel treatment option for the Crohn's fistula with high-risk of recurrence. Copyright © 2013 AlphaMed Press.

  19. An agonistic monoclonal antibody against DR5 induces ROS production, sustained JNK activation and Endo G release in Jurkat leukemia cells

    Institute of Scientific and Technical Information of China (English)

    Caifeng Chen; Yanxin Liu; Dexian Zheng

    2009-01-01

    We have previously reported that AD5-10, a novel agonistic monoclonal antibody against DRS, possessed a strong cytotoxic activity in various tumor cells, via induction of caspase-dependent and-independent signaling pathways. The present study further demonstrates that reactive oxygen species (ROS) were generated in abundance in Jurkat leukemia cells upon ADS-10 stimulation and that ROS accumulation subsequently evoked sustained activation of c-Jun N-terminal kinase (JNK), loss of mitochondrial membrane potential, and release of endonuclease G (Endo G) from mitochondria into the cytosol. The reducing agent, N-acetylcysteine (NAC), effectively inhibited the sustained activation of JNK, release of Endo G, and cell death in Jurkat cells treated by ADS-10. Moreover, a dominant-nega-tive form of JNK (but not of p38) enhanced NF-KB activation, suppressed caspase-8 recruitment in death-inducing signaling complexes (DISCs), and reduced adverse effects on mitochondria, thereby inhibiting AD5-10-induced cell death in Jurkat leukemia cells. These data provide novel information on the DRS-mediated cell death-signaling path-way and may shed new light on effective strategies for leukemia and solid tumor therapies.

  20. Doxycycline sustained release from brushite cements for the treatment of periodontal diseases.

    Science.gov (United States)

    Tamimi, Faleh; Torres, Jesús; Bettini, Ruggero; Ruggera, Francesca; Rueda, Carmen; López-Ponce, Manuel; Lopez-Cabarcos, Enrique

    2008-06-01

    Doxycycline (DOXY) is a wide spectrum antibiotic used in the treatment of dental, periodontal, and bone infections. Brushite cements are calcium phosphate biomaterials especially interesting for bone regeneration processes. In this work, we describe the preparation of a brushite cement containing DOXY and the drug release from the cement. DOXY solutions were mixed with the cement powder and after a 50% burst release in the first 12 h, a slow and controlled release was achieved over 3.5 days. The release of DOXY hyclate was controlled by both, diffusion and Ca(2+) interaction. Formation of DOXY-Ca(2+) chelates was detected in the cement structure using solid state fluorescence. The brushite cement loaded with DOXY hyclate had antibacterial activity against periodontal pathogens: Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, and Bacteroides frosthytus. This new biomaterial may be helpful for the treatment of periodontal diseases. Copyright 2007 Wiley Periodicals, Inc.

  1. Effect of pretreatment with ranitidine on the pharmacokinetics and gastrointestinal transit of a sustained release theophylline preparation.

    Science.gov (United States)

    Wilson, C G; Washington, N; Greaves, J L; Blackshaw, P E; Perkins, A C; Barkworth, M F; Rehm, K D

    1991-11-01

    A scintigraphic and pharmacokinetic study of the behaviour of (Bronchoretard forte, CAS 58-55-9) was carried out in 8 healthy male volunteers to evaluate the sensitivity of the preparation to changes in gastric pH. Volunteers were pretreated with ranitidine (CAS 66357-35-5) (150 mg b.d.) or placebo for three days prior to and on the study day to reduce gastric acidity. The effect of the pretreatment with ranitidine on gastric pH was measured on the prestudy day and the mean pH was significantly reduced compared to the placebo (ranitidine pH 2.2 +/- 2.4; placebo pH 1.6 +/- 2.0, p less than 0.01 Wilcoxon Signed Rank test). All subjects were pretreated with theophylline for 3 days (500 mg b.d.) to achieve steady-state. On the study day the volunteers swallowed two theophylline sustained release capsules radiolabelled by inclusion of indium-111 micronised Amberlite resin and the gastrointestinal transit followed continuously for 14 h using gamma scintigraphy with a further image at 24 h. Blood samples were taken from each subject throughout the study to determine the pharmacokinetic profile of theophylline when presented in the sustained release formulation. No significant differences were found in the gastrointestinal transit of the labelled microparticulates between the data obtained from the group when treated with ranitidine or placebo. Plasma theophylline concentration profiles were identical for the two treatments. These data indicate that the theophylline sustained release formulation is not sensitive to the effects of major changes in gastric H+ concentration.

  2. 石杉碱甲双层缓释片的研制及体外释药研究%Preparation of Huperzine A Double - layer Sustained Release Tablets and Their in Vitro Release Charac-teristics

    Institute of Scientific and Technical Information of China (English)

    周红祖; 刘湘丹; 余惠雯

    2009-01-01

    目的:研制石杉碱甲双层缓释片并考察其体外释药特征.方法:缓释层以HPMC K4M为缓释骨架材料,乳糖为稀释剂;速释层以淀粉-碳酸钙为稀释剂,羧甲基淀粉钠为崩解剂,压制双层片,高效液相色谱法检测释放度.结果:制备的石杉碱甲双层片速释层在1~2 min崩解,呈粉末状,符合要求;缓释层的释药曲线用Higuehi方程拟合,可维持12 h释药.结论:该处方下研制的石杉碱甲双层缓释片可达到既速效又长效的目的.%OBJECTIVE: To study the preparation of Huperzine- A double- layer sustained release tablets and their in vitro release characteristics. METHODS: With HPMC K4M as matrix and lactose as diluting agent for the sustained release layer, and with starch - calcium carbonate as diluting agent and sodium carboxymethyl starch as disintegrating agent for the fast release layer to prepare the double- layer tablets by compression, with the release rate of the compressed tablets deter-mined by HPLC. RESULTS: The fast release layer of the prepared Huperzine- A double- layer tablets disintegrated within 1~2 min and appeared as fine powder, meeting the requirement; the release curve of the sustained release layer of the tablets was in line with Higuchi equation and maintained a sustained release of 12 hours. CONCLUSION: The prepared Huperzine-A double - layer tables achieved the goal of both immediate release and sustained release.

  3. Sustained release of risperidone from biodegradable microspheres prepared by in-situ suspension-evaporation process.

    Science.gov (United States)

    An, Taekun; Choi, Juhyuen; Kim, Aram; Lee, Jin Ho; Nam, Yoonjin; Park, Junsung; Sun, Bo kyung; Suh, Hearan; Kim, Cherng-ju; Hwang, Sung-Joo

    2016-04-30

    Risperidone-loaded poly (D,L-lactide-co-glycolide) (PLGA) microspheres were prepared with a suspension-evaporation process with an aqueous suspension containing an in situ-formed aluminum hydroxide inorganic gel (SEP-AL process) and evaluated for encapsulation efficiency, particle size, surface morphology, glass transition temperature, in vitro drug release profile, and in vivo behavior. The SEP-AL microspheres were compared with conventional oil-in-water (O/W) emulsion solvent evaporation method using polyvinylalcohol (PVA) as an emulsifier (CP-PVA process). The microspheres were spherical in shape. DSC measurements showed that risperidone crystallinity was greatly reduced due to the homogeneous distribution of risperidone in PLGA microspheres. In vitro drug release profile from the microspheres showed a sigmoidal pattern of negligible initial burst up to 24h and minimal release (time-lag) for 7 days. After the lag phase, slow release took a place up to 25 days and then rapid release occurred sharply for 1 week. In vivo rat pharmacokinetic profile from the microspheres showed very low blood concentration level at the initial phase (up to 24h) followed by the latent phase up to 21 days. At the 3rd week, main phase started and the blood concentration of the drug increased up to the 5th week, and then gradually decreased. The risperidone-loaded PLGA microspheres produced by SEP-AL process showed excellent controlled release characteristics for the effective treatment of schizophrenia patients.

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

    DEFF Research Database (Denmark)

    Andersen, O; Nielsen, M K; Eriksen, P B;

    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...... formulation, whereas this was not the case for the other (r = 0.27 and 0.49). The daily dose necessary to keep the plasma concentration within the therapeutic range of 55-110 mumole/liter varied from 7.9 to 22.9 mg/kg. Only mild side effects were recorded, but they were not correlated to the plasma...... theophylline concentration....

  5. 美乐托宁缓释片在不同介质中的释放试验%Study on the release of melatonin sustained release tablets in different mediums

    Institute of Scientific and Technical Information of China (English)

    杨大龙; 杨意波; 卢定强; 谢浩; 严相平

    2012-01-01

    OBJECTIVE To prepare melatonin sustained release tablets. Melatonin sustained release lahlets were used as reference preparation, which have been licensed overseas. And the release behavior similarity was investigated between reference preparation tablets and self-prepared preparation in release mediums with different pH, the in vitro drug release mechanism also was investgated. METHODS The release tests were carried out with rotating basket, HPLC method was used to determine the release of melatonin sustained release tablets, the f2 similarity factor was used to evaluate the similarity of release curves. RESULTS In different release mediums, the release curves of melatonin sustained release tablets from self-prepared preparation compared with reference preparation, similar factor(f2) are all more than 50; In vitro drug release of melatonin sustained release tablets was consistent with first-class equation, Higuchi equation and Peppas equation in 4 kinds of medium. CONCLUSION The release behavior of self-prepared preparation and reference preparation were similar in release mediums with differ ent pH, the release mechanism was diffusion drug release.%目的:制备美乐托宁缓释片,以国外上市制剂美乐托宁缓释片为参比制剂,考察自研制剂和参比制剂在不同pH释放介质中体外释放行为的相似性及体外释药机制.方法:采用释放度测定法转篮法的装置进行体外释放实验,用HPLC法测定释放度,采用f2相似因子对2种制剂释放曲线的相似度进行评价,并进行释放行为模型的拟合.结果:在不同pH的释放介质中,自制制剂释放度曲线与参比制剂比较,f2相似因子均大于50;美乐托宁缓释片在4种释放介质中体外释药拟合模型更接近一级方程、Higuchi方程和Peppas方程.结论:参比制剂与自制制剂在不同pH释放介质中的体外释放一致,释放机制为扩散释药.

  6. Light Water Reactor Sustainability Program Risk Informed Safety Margin Characterization (RISMC) Advanced Test Reactor Demonstration Case Study

    Energy Technology Data Exchange (ETDEWEB)

    Curtis Smith; David Schwieder; Cherie Phelan; Anh Bui; Paul Bayless

    2012-08-01

    Safety is central to the design, licensing, operation, and economics of Nuclear Power Plants (NPPs). Consequently, the ability to better characterize and quantify safety margin holds the key to improved decision making about LWR design, operation, and plant life extension. A systematic approach to characterization of safety margins and the subsequent margins management options represents a vital input to the licensee and regulatory analysis and decision making that will be involved. The purpose of the RISMC Pathway R&D is to support plant decisions for risk-informed margins management with the aim to improve economics, reliability, and sustain safety of current NPPs. Goals of the RISMC Pathway are twofold: (1) Develop and demonstrate a risk-assessment method coupled to safety margin quantification that can be used by NPP decision makers as part of their margin recovery strategies. (2) Create an advanced “RISMC toolkit” that enables more accurate representation of NPP safety margin. This report describes the RISMC methodology demonstration where the Advanced Test Reactor (ATR) was used as a test-bed for purposes of determining safety margins. As part of the demonstration, we describe how both the thermal-hydraulics and probabilistic safety calculations are integrated and used to quantify margin management strategies.

  7. ACETYLATION AND CHARACTERIZATION OF ENSET STARCH AND EVALUATION OF ITS DIRECT COMPRESSION AND DRUG RELEASE SUSTAINING PROPERTIES

    Directory of Open Access Journals (Sweden)

    Efrem Nigussu, Anteneh Belete and Tsige Gebre-Mariam*

    2013-11-01

    Full Text Available Enset (Ensete ventricosum, Musaceae, a plant widely cultivated in south and southwest of Ethiopia, has been shown to be a rich source of starch. In an effort to produce directly compressible matrix-forming excipient, native enset starch was acetylated. Starch acetates (SA with degrees of substitution (DS of 0.672 and 2.142 were evaluated. Fourier transform infrared (FTIR spectra of the modified starches verified the acetylation of the starch molecules. Further investigations revealed that acetylation increased swelling power and solubility, improved flow property and compactability of the starch. The tensile strength of SA matrix tablets increased with an increase in DS. Plain tablets of SA with DS 0.672 disintegrated within 3 min while those of SA with DS 2.142 did not disintegrate over a period of 2 h. Dissolution studies of theophylline loaded SA tablets conducted in 0.1 N HCl for the first 1.5 h and in phosphate buffer pH 6.8 for the remaining study time revealed the change in drug release rate from rapid to sustained release (>12 h as the DS increased from 0.672 to 2.142. The dissolution data obtained best fitted Higuchi model with R2 > 0.99. The drug release diffusional exponent (n, obtained from Korsemeyer-Peppas model, varied between 0.4899 - 0.6369 for different theophylline/SA ratios and the goodness of the fit was > 0.99 in each case which indicated the deviation from Fickian diffusion. Accordingly, high degree of acetylation renders enset starch highly compressible and suitable for sustained release formulations that makes it amenable for use as an alternative pharmaceutical excipient.

  8. Surgical wound healing using hemostatic gauze scaffold loaded with nanoparticles containing sustained-release granulocyte colony-stimulating factor

    Directory of Open Access Journals (Sweden)

    Yuan W

    2011-12-01

    Full Text Available Weien Yuan1,2, Zhenguo Liu11Department of Neurology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 2School of Pharmacy, Shanghai Jiao Tong University, Shanghai, People's Republic of ChinaBackground: The therapeutic strategies for malignant melanoma are still cancer chemotherapy, radiotherapy, and tumor resection. However, these therapeutic strategies often lead to a reduced neutrophilic granulocyte count or loss of more blood after surgical tumor resection. In this study, we developed a formulation of hemostatic gauze impregnated with sustained-release granulocyte colony-stimulating factor (G-CSF with increasing of the neutrophilic granulocyte count in the blood following chemotherapy and decreasing blood loss after surgical tumor resection.Methods: We designed a formulation with both hemostatic properties and increased neutrophil content to be used in cancer chemotherapy, radiotherapy, and tumor resection, comprising a hemostatic gauze as a scaffold and (G-CSF-loaded dextran nanoparticles coated with polylactic-co-glycolic acid (PLGA solution fabricated by direct spray-painting onto the scaffold and then vacuum-dried at room temperature. The performance of this system was evaluated in vitro and in vivo.Results: Nearly zero-order release of G-CSF was recorded for 12–14 days, and the cumulative release of G-CSF retained over 90% of its bioactivity in a NFS-60 cell line proliferation assay when the scaffold was incubated in phosphate-buffered saline (pH 7.4 at 37°C. The in vivo hemostatic efficacy of this formulation was greater than that of native G-CSF, the scaffold directly spray-painted with G-CSF solution or PLGA organic solution as a coating, or when a blank scaffold was covered with the coating.Conclusion: Our results suggest that this formulation has both hemostatic properties and increased neutrophil activity.Keywords: hemostatic gauze scaffold, granulocyte colony-stimulating factor, bioactivity

  9. Effect of polysulfonate resins and direct compression fillers on multiple-unit sustained-release dextromethorphan resinate tablets.

    Science.gov (United States)

    Pongjanyakul, Thaned; Priprem, Aroonsri; Chitropas, Padungkwan; Puttipipatkhachorn, Satit

    2005-09-30

    The purpose of this work was to investigate the effect of different polysulfonate resins and direct compression fillers on physical properties of multiple-unit sustained-release dextromethorphan (DMP) tablets. DMP resinates were formed by a complexation of DMP and strong cation exchange resins, Dowex 50 W and Amberlite IRP69. The tablets consisted of the DMP resinates and direct compression fillers, such as microcrystalline cellulose (MCC), dicalcium phosphate dihydrate (DCP), and spray-dried rice starch (SDRS). Physical properties of tablets, such as hardness, disintegration time, and in vitro release, were investigated. A good performance of the tablets was obtained when MCC or SDRS was used. The use of rod-like and plate-like particles of Amberlite IRP69 caused a statistical decrease in tablet hardness, whereas good tablet hardness was obtained when spherical particle of Dowex 50 W was used. The plastic deformation of the fillers, such as MCC and SDRS, caused a little change in the release of DMP. A higher release rate constant was found in the tablets containing DCP and Dowex 50 W, indicating the fracture of the resinates under compression, which was attributable to the fragmentation of DCP. However, the release of DMP from the tablets using Amberlite IRP69 was not significantly changed because of the higher degree of cross-linking of the resinates, which exhibited more resistance to deformation under compression. In conclusion, the properties of polysulfonate resin, such as particle shape and degree of cross-linking, and the deformation under compaction of fillers affect the physical properties and the drug release of the resinate tablets.

  10. Design and In-vitro Evaluation of Sustained Release Floating Tablets of Metformin HCl Based on Effervescence and Swelling.

    Science.gov (United States)

    Senjoti, Faria Gias; Mahmood, Syed; Jaffri, Juliana Md; Mandal, Uttam Kumar

    2016-01-01

    An oral sustained-release floating tablet formulation of metformin HCl was designed and developed. Effervescence and swelling properties were attributed on the developed tablets by sodium bicarbonate and HPMC-PEO polymer combination, respectively. Tablet composition was optimized by response surface methodology (RSM). Seventeen (17) trial formulations were analyzed according to Box-Behnken design of experiment where polymer content of HPMC and PEO at 1: 4 ratio (A), amount of sodium bi-carbonate (B), and amount of SSG (C) were adopted as independent variables. Floating lag time in sec (Y1), cumulative percent drug released at 1 h (Y2) and 12 h (Y3) were chosen as response variables. Tablets from the optimized formulation were also stored at accelerated stability condition (40°C and 75% RH) for 3 months to assess their stability profile. RSM could efficiently optimize the tablet composition with excellent prediction ability. In-vitro drug release until 12 h, floating lag time, and duration of floating were dependent on the amount of three selected independent variables. Optimized tablets remained floating for more than 24 h with a floating lag time of less than 4 min. Based on best fitting method, optimized formulation was found to follow Korsmeyer-Peppas release kinetic. Accelerated stability study revealed that optimized formulation was stable for three months without any major changes in assay, dissolution profile, floating lag time and other physical properties.

  11. Sustained release of vancomycin from novel biodegradable nanofiber-loaded vascular prosthetic grafts: in vitro and in vivo study

    Directory of Open Access Journals (Sweden)

    Liu KS

    2015-01-01

    Full Text Available Kuo-Sheng Liu,1 Cheng-Hung Lee,2 Yi-Chuan Wang,3 Shih-Jung Liu3 1Department of Thoracic and Cardiovascular Surgery, Chang Gung Memorial Hospital, Linkou, Taiwan; 2Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Linkou, Taiwan; 3Department of Mechanical Engineering, Chang Gung University, Tao-Yuan, Taiwan Abstract: This study describes novel biodegradable, drug-eluting nanofiber-loaded vascular prosthetic grafts that provide local and sustained delivery of vancomycin to surrounding tissues. Biodegradable nanofibers were prepared by first dissolving poly(D,L-lactide-co-glycolide and vancomycin in 1,1,1,3,3,3-hexafluoro-2-propanol. The solution was then electrospun into nanofibers onto the surface of vascular prostheses. The in vitro release rates of the pharmaceutical from the nanofiber-loaded prostheses was characterized using an elution method and a high-performance liquid chromatography assay. Experimental results indicated that the drug-eluting prosthetic grafts released high concentrations of vancomycin in vitro (well above the minimum inhibitory concentration for more than 30 days. In addition, the in vivo release behavior of the drug-eluting grafts implanted in the subcutaneous pocket of rabbits was also documented. The drug-eluting grafts developed in this work have potential applications in assisting the treatment of vascular prosthesis infection and resisting reinfection when an infected graft is to be exchanged. Keywords: drug-eluting prosthetic graft, vascular prosthesis infection, release characteristics

  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

    2011-03-15

    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.

  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. Collagen biomineralization In Vivo by sustained release of inorganic phosphate ions

    NARCIS (Netherlands)

    Habibovic, Pamela; Bassett, David C.; Doillon, Charles J.; Gerard, Catherine; McKee, Marc D.; Barralet, Jake E.

    2010-01-01

    A new strategy for mineralized tissue formation in vivo is presented based on localized sustained delivery of inorganic orthophosphate (Pi) sufficient to supersaturate tissue surrounding an implant and induce mineralization of collagen. After 15 days implantation mineral formation around the implant

  15. Layered double hydroxides as supports for intercalation and sustained release of antihypertensive drugs

    Science.gov (United States)

    Xia, Sheng-Jie; Ni, Zhe-Ming; Xu, Qian; Hu, Bao-Xiang; Hu, Jun

    2008-10-01

    Zn/Al layered double hydroxides (LDHs) were intercalated with the anionic antihypertensive drugs Enalpril, Lisinopril, Captopril and Ramipril by using coprecipitation or ion-exchange technique. TG-MS analyses suggested that the thermal stability of Ena -, Lis - (arranged with monolayer, resulted from X-ray diffraction (XRD) and Fourier transform infrared spectra (FT-IR) analysis was enhanced much more than Cap - and Ram - (arranged with bilayer). The release studies show that the release rate of all samples markedly decreased in both pH 4.25 and 7.45. However, the release time of Ena -, Lis - were much longer compared with Cap -, Ram - in both pH 4.25 and 7.45, it is possible that the intercalated guests, arranged with monolayer in the interlayer, show lesser repulsive force and strong affinity with the LDH layers. And the release data followed both the Higuchi-square-root law and the first-order equation well. Based on the analysis of batch release, intercalated structural models as well as the TG-DTA results, we conclude that for drug-LDH, stronger the affinity between intercalated anions and the layers is, better the thermal property and the stability to the acid attack of drug-LDH, and the intercalated anions are easier apt to monolayer arrangement within the interlayer, were presented.

  16. 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

    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...

  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. Sustained-release microsphere formulation containing an agrochemical by polyurethane polymerization during an agitation granulation process.

    Science.gov (United States)

    Terada, Takatoshi; Tagami, Manabu; Ohtsubo, Toshiro; Iwao, Yasunori; Noguchi, Shuji; Itai, Shigeru

    2016-07-25

    In this report, a new solventless microencapsulation method by synthesizing polyurethane (PU) from polyol and isocyanate during an agglomeration process in a high-speed mixing apparatus was developed. Clothianidin (CTD), which is a neonicotinoid insecticide and highly effective against a wide variety of insect pests, was used as the model compound. The microencapsulated samples covered with PU (CTD microspheres) had a median diameter of dispersed in PU. Although voids appeared in the CTD microspheres after CTD release, the spherical shape of the microspheres remained stable and no change in its framework was observed. The experimental release data were highly consistent with the Baker-Lonsdale model derived from drug release of spherical monolithic dispersions and consistent with the computed tomography measurements.

  19. Lumbar interbody fusion with porous biphasic calcium phosphate enhanced by recombinant bone morphogenetic protein-2/silk fibroin sustained-released microsphere: an experimental study on sheep model.

    Science.gov (United States)

    Chen, Liang; Liu, Hai-Long; Gu, Yong; Feng, Yu; Yang, Hui-Lin

    2015-03-01

    Biphasic calcium phosphate (BCP) has been investigated extensively as a bone substitute nowadays. However, the bone formation capacity of BCP is limited owing to lack of osteoinduction. Silk fibroin (SF) has a structure similar to type I collagen, and could be developed to a microsphere for the sustained-release of rhBMP-2. In our previous report, bioactivity of BCP could be enhanced by rhBMP-2/SF microsphere (containing 0.5 µg rhBMP-2) in vitro. However, the bone regeneration performance of the composite in vivo was not investigated. Thus, the purpose of this study was to evaluate the efficacy of BCP/rhBMP-2/SF in a sheep lumbar fusion model. A BCP and rhBMP-2/SF microsphere was developed, and then was integrated into a BCP/rhBMP-2/SF composite. BCP, BCP/rhBMP-2 and BCP/rhBMP-2/SF were implanted randomly into the disc spaces of 30 sheep at the levels of L1/2, L3/4 and L5/6. After sacrificed, the fusion segments were evaluated by manual palpation, CT scan, biomechanical testing and histology at 3 and 6 months, respectively. The composite demonstrated a burst-release of rhBMP-2 (39.1 ± 2.8 %) on the initial 4 days and a sustained-release (accumulative 81.3 ± 4.9 %) for more than 28 days. The fusion rates, semi-quantitative CT scores, fusion stiffness in bending in all directions and histologic scores of BCP/rhBMP-2/SF were significantly greater than BCP and BCP/rhBMP-2 at each time point, respectively (P sheep using BCP constructs.

  20. SUSTAINABILITY LOGISTICS BASING SCIENCE AND TECHNOLOGY OBJECTIVE DEMONSTRATION; 50, 300, 1000 PERSON BASE CAMP, ANALYSIS OF FY12 OPERATIONALLY RELEVANT TECHNICAL BASELINE

    Science.gov (United States)

    2017-04-10

    BASING – SCIENCE AND TECHNOLOGY OBJECTIVE – DEMONSTRATION; 50, 300, 1000-PERSON BASE CAMP, ANALYSIS OF FY12 OPERATIONALLY RELEVANT TECHNICAL...REPORT TYPE Final 3. DATES COVERED (From - To) January 2012 – November 2016 4. TITLE AND SUBTITLE SUSTAINABILITY LOGISTICS BASING – SCIENCE AND...Natick Soldier Research, Development and Engineering Center’s Sustainability/Logistics-Basing - Science and Technology Objective – Demonstration to

  1. 玫瑰香精纳米胶囊加香缓释棉织物的性能研究%Properties of Aroma Sustained-release Cotton Fabric with Rose Fragrance Nanocapsule

    Institute of Scientific and Technical Information of China (English)

    胡静; 肖作兵; 周如隽; 马双双; 王明熙; 李臻

    2011-01-01

    The aroma sustained-release cotton fabric was prepared by finishing rose fragrance nanocapsules directly on cotton. The structure and properties of nanocapsules were demonstrated by transmission electron microscope (TEM), dynamic light scattering (DLS), fourier transform infrared spectrometer (FTIR), X-ray diffraction (XRD), gas chromatography-mass spectrometry (GC-MS) and electronic nose. The results showed that the spherical nanocapsule dispersed evenly and the average diameter kept 51.4 nm. The existence of -COO peak (1741 cm-) in the FTIR curve of the finished cotton fabric and the decrease of crystallinity demonstrated that rose fragrance nanocapsules have been incorporated into the cotton fabrics. The washing resistance of the cotton fabrics finished by 51.4 nm nanocapsules was much better than that by rose fragrance alone. Besides, the loss of fragrance from the cotton fabrics finished by 51.4 nm nanocapsules was obviously lower than that by 532 nm nanocapsules and rose fragrance. The smaller the nanocapsule size, the better the sustained release property. Electronic nose analysis also displayed that the aroma released from the cotton fabrics finished by nanocapsules after washing has no obvious variety in contrast to that without washing. The cotton fabrics finished by nanocapsules has the excellent sustained release property.

  2. Sustained release of bone morphogenetic protein 2 via coacervate improves the osteogenic potential of muscle-derived stem cells.

    Science.gov (United States)

    Li, Hongshuai; Johnson, Noah Ray; Usas, Arvydas; Lu, Aiping; Poddar, Minakshi; Wang, Yadong; Huard, Johnny

    2013-09-01

    Muscle-derived stem cells (MDSCs) isolated from mouse skeletal muscle by a modified preplate technique exhibit long-term proliferation, high self-renewal, and multipotent differentiation capabilities in vitro. MDSCs retrovirally transduced to express bone morphogenetic proteins (BMPs) can differentiate into osteocytes and chondrocytes and enhance bone and articular cartilage repair in vivo, a feature that is not observed with nontransduced MDSCs. These results emphasize that MDSCs require prolonged exposure to BMPs to undergo osteogenic and chondrogenic differentiation. A sustained BMP protein delivery approach provides a viable and potentially more clinically translatable alternative to genetic manipulation of the cells. A unique growth factor delivery platform comprised of native heparin and a synthetic polycation, poly(ethylene argininylaspartate diglyceride) (PEAD), was used to bind, protect, and sustain the release of bone morphogenetic protein-2 (BMP2) in a temporally and spatially controlled manner. Prolonged exposure to BMP2 released by the PEAD:heparin delivery system promoted the differentiation of MDSCs to an osteogenic lineage in vitro and induced the formation of viable bone at an ectopic site in vivo. This new strategy represents an alternative approach for bone repair mediated by MDSCs while bypassing the need for gene therapy.

  3. Demonstration of Decision Support Tools for Sustainable Development - An Application on Alternative Fuels in the Greater Yellowstone-Teton Region

    Energy Technology Data Exchange (ETDEWEB)

    Shropshire, D.E.; Cobb, D.A.; Worhach, P.; Jacobson, J.J.; Berrett, S.

    2000-12-30

    The Demonstration of Decision Support Tools for Sustainable Development project integrated the Bechtel/Nexant Industrial Materials Exchange Planner and the Idaho National Engineering and Environmental Laboratory System Dynamic models, demonstrating their capabilities on alternative fuel applications in the Greater Yellowstone-Teton Park system. The combined model, called the Dynamic Industrial Material Exchange, was used on selected test cases in the Greater Yellow Teton Parks region to evaluate economic, environmental, and social implications of alternative fuel applications, and identifying primary and secondary industries. The test cases included looking at compressed natural gas applications in Teton National Park and Jackson, Wyoming, and studying ethanol use in Yellowstone National Park and gateway cities in Montana. With further development, the system could be used to assist decision-makers (local government, planners, vehicle purchasers, and fuel suppliers) in selecting alternative fuels, vehicles, and developing AF infrastructures. The system could become a regional AF market assessment tool that could help decision-makers understand the behavior of the AF market and conditions in which the market would grow. Based on this high level market assessment, investors and decision-makers would become more knowledgeable of the AF market opportunity before developing detailed plans and preparing financial analysis.

  4. Preparation and In Vitro-In Vivo Evaluation of Sustained-Release Matrix Pellets of Capsaicin to Enhance the Oral Bioavailability.

    Science.gov (United States)

    Zhang, Ya; Huang, Zhimin; Omari-Siaw, E; Lu, Shuang; Zhu, Yuan; Jiang, Dongmei; Wang, Miaomiao; Yu, Jiangnan; Xu, Ximing; Zhang, Weiming

    2016-04-01

    Capsaicin has multiple pharmacological activities including antioxidant, anticancer, and anti-inflammatory activities. However, its clinical application is limited due to its poor aqueous solubility, gastric irritation, and low oral bioavailability. This research was aimed at preparing sustained-release matrix pellets of capsaicin to enhance its oral bioavailability. The pellets comprised of a core of solid-dispersed capsaicin mixed with microcrystalline cellulose (MCC) and hydroxypropyl cellulose (HPMC) and subsequently coating with ethyl cellulose (EC) were obtained by using the technology of extrusion/spheronization. The physicochemical properties of the pellets were evaluated through scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and X-ray diffractometry (XRD). Besides, the in vitro release, in vivo absorption, and in vitro-in vivo correlation were also assessed. More importantly, the relative bioavailability of the sustained-release matrix pellets was studied in fasted rabbits after oral administration using free capsaicin and solid dispersion as references. The oral bioavailability of the matrix pellets and sustained-release matrix pellets of capsaicin was improved approximately 1.98-fold and 5.34-fold, respectively, compared with the free capsaicin. A good level A IVIVC (in vitro-in vivo correlation) was established between the in vitro dissolution and the in vivo absorption of sustained-release matrix pellets. All the results affirmed the remarkable improvement in the oral bioavailability of capsaicin owing to the successful preparation of its sustained-release matrix pellets.

  5. 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

    is still high. We conclude that Doc2b acts to inhibit vesicle priming during prolonged calcium elevations, thus protecting unprimed vesicles from fusing prematurely, and redirecting them to refill the readily releasable pool after relaxation of the calcium signal. In sum, Doc2b favors fast, synchronized...

  6. Magnetic glass ceramics for sustained 5-fluorouracil delivery: characterization and evaluation of drug release kinetics.

    Science.gov (United States)

    Abdel-Hameed, S A M; El-Kady, A M; Marzouk, M A

    2014-11-01

    In the present study, magnetic glass ceramics in the system Fe2O3 ∙ TiO2 ∙ P2O5 ∙ SiO2 ∙ MO (M=Mg, Ca, Mn, Cu, Zn or Ce) are prepared. The effect of adding different cations on the thermal behavior, developed phases, microstructure and magnetic properties is studied using differental thermal analysis (DTA), X-ray diffraction analysis (XRD), transmission electron microscope (TEM), FT-infrared transmission (FT-IR) and vibrating sample magnetometer (VSM) respectively. The magnetic glass ceramics are tested as delivery systems for 5-fluorouracil. Modeling and analysis of release kinetics are addressed. The application of Higuchi square root of time model and the first order release model indicated that, 5-FU is released by diffusion controlled mechanisms, and that its released rate depends greatly on the concentration of loaded drug during the loading stage. The obtained results suggested that, the prepared magnetic glass ceramics can be used for cancer treatment by hyperthermia and/or by localized delivery of therapeutic doses of 5-fluorouracil.

  7. Hydrogels of collagen-inspired telechelic triblock copolymers for the sustained release of proteins

    NARCIS (Netherlands)

    Teles, H.M.; Vermonden, T.; Eggink, G.

    2010-01-01

    We studied the release of entrapped protein from transient gels made of thermosensitive, collagen-inspired ABA triblock copolymers with tailorable properties and with mid blocks of two different lengths (~ 37 kDa and ~ 73 kDa). These polymers were produced as heterologous proteins in recombinant yea

  8. Stability aspects of salmon calcitonin entrapped in poly(ether-ester) sustained release systems

    NARCIS (Netherlands)

    Dijkhuizen-Radersma, van R.; Nicolas, H.M.; Weert, van de M.; Blom, M.; Groot, de K.; Bezemer, J.M.

    2002-01-01

    Poly(ether-ester)s composed of hydrophilic poly(ethylene glycol)-terephthalate (PEGT) blocks and hydrophobic poly(butylene terephthalate) (PBT) blocks were studied as matrix for the controlled release of calcitonin. Salmon calcitonin loaded PEGT/PBT films were prepared from water-in-oil emulsions. T

  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.

  10. New formulation of an old drug in hypertension treatment: the sustained release of captopril from cyclodextrin nanoparticles

    Directory of Open Access Journals (Sweden)

    de Azevedo MB

    2011-05-01

    observed upon CAP administration. The nanoparticles obtained by the kneading method (CAP/α-CD:KM showed a potent and long-lasting inhibitory activity (~22 hours on the angiotensin I pressor effect. The results suggest that the inclusion complex of CAP and α-CD can function as a novel antihypertensive formulation that may improve therapeutic use of CAP by reducing its oral dose administration to once per day, thus providing better quality of life for almost 25% of the world's population who suffer from hypertension.Keywords: captopril, cyclodextrin nanoparticles, sustained release

  11. Sustained Release of Bone Morphogenetic Protein 2 via Coacervate improves Muscle Derived Stem Cell Mediated Cartilage Regeneration in MIA-induced Osteoarthritis

    Science.gov (United States)

    Hicks, Justin James; Rocha, Jorge Luis; Li, Hongshuai; Huard, Johnny; Wang, Yadong; Hogan, MaCalus Vinson

    2016-01-01

    Objectives: Individuals who participate in sports have an increased risk of osteoarthritis (OA), characterized by articular cartilage degeneration. Currently, there is no cure for OA with treatment aimed at symptom relief and improved function. Muscle-derived stem cells (MDSCs) have been shown to exhibit long-term proliferation, high self-renewal, and multipotent differentiation capabilities in vitro. Previously, we have demonstrated that murine MDSCs retrovirally transduced to express chondrogenic proteins (BMPs) differentiate into chondrocytes and enhance cartilage repair in vivo. Direct injection of therapeutic proteins can promote cartilage healing; however, they have relatively short half-lives requiring muitiple injections of high dosages. This presents a challenge in terms of maintaining adequate local BMP levels and could negatively affect both injured and normal structures and lead to side effects such as osteophyte formation. Gene therapy is a promising approach that addresses this problem; however, its utilization in clinical applications is much further down the road. In order to circumvent viral transduction of cells for cartilage regeneration, we developed a unique growth factor delivery platform comprised of native heparin and a synthetic polycation, poly(ethylene argininylaspartate diglyceride) (PEAD) incorporated with BMP2 (BMP2 coacervate). In this study, we show that sustained delivery of BMP2 via a BMP2 coacervate can induce the differentiation of MDSCs to a chondrocyte lineage for in vivo cartilage regeneration and healing in a Monoiodoacetate (MIA)-induced osteoarthritis model. Methods: mMDSCs were isolated from muscle biopsies via a modified pre-plated technique. The BMP2 coacervates were prepared as previously described. The release profiles of BMP2 coacervate were tested by ELISA. The chondrogenic effects that delivery of BMP2 had on MDSCs were evaluated by RT-PCR. The efficacy of MDSC with BMP2 coacervate were evaluated in vivo in a MIA

  12. [EVALUETION OF THE CLINICAL EFFICACY OF SUSTAINED RELEASE THEOPHILLINE IN A COMPLEX BASIC THERAPY OF EOSINOPHILIC PHENOTYPE OF BRONCHIAL ASTHMA IN SCHOOL AGE CHILDREN].

    Science.gov (United States)

    Ortemenka, Ye P

    2014-01-01

    Based on a complex examination of 11 school age children with eosinophilic phenotype of bronchial asthma, it has been demonstrated that combination of inhaled corticosteroids with oral sustained release theophillines were more effective as a basic anti-inflammatory asthma therapy, in comparison with monotherapy by inhaled corticosteroids. The usage of such combined anti-relapsing asthma treatment has been reduced both the relative risk (RR = 57%) and the attributable risk (AR = 36.3%) of insufficient control of bronchial asthma in children with eosinophilic type of airways inflammation. At the same time, the minimum number of patients, which have to be treated by such method with the object of preventing at least one case of poor asthma control, came to 3 children.

  13. Modified Silicone Elastomer Vaginal Gels for Sustained Release of Antiretroviral HIV Microbicides

    OpenAIRE

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

    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 counte...

  14. Magnetic glass ceramics for sustained 5-fluorouracil delivery: Characterization and evaluation of drug release kinetics

    Energy Technology Data Exchange (ETDEWEB)

    Abdel-Hameed, S.A.M., E-mail: Salwa_NRC@hotmail.com [Glass Research Department, National Research Center, Dokki, ElBehoos St., Cairo 12311 (Egypt); El-Kady, A.M. [Biomaterial Department, National Research Center, Dokki, ElBehoos St., Cairo 12311 (Egypt); Marzouk, M.A. [Glass Research Department, National Research Center, Dokki, ElBehoos St., Cairo 12311 (Egypt)

    2014-11-01

    In the present study, magnetic glass ceramics in the system Fe{sub 2}O{sub 3} ∙ TiO{sub 2} ∙ P{sub 2}O{sub 5} ∙ SiO{sub 2} ∙ MO (M = Mg, Ca, Mn, Cu, Zn or Ce) are prepared. The effect of adding different cations on the thermal behavior, developed phases, microstructure and magnetic properties is studied using differental thermal analysis (DTA), X-ray diffraction analysis (XRD), transmission electron microscope (TEM), FT-infrared transmission (FT-IR) and vibrating sample magnetometer (VSM) respectively. The magnetic glass ceramics are tested as delivery systems for 5-fluorouracil. Modeling and analysis of release kinetics are addressed. The application of Higuchi square root of time model and the first order release model indicated that, 5-FU is released by diffusion controlled mechanisms, and that its released rate depends greatly on the concentration of loaded drug during the loading stage. The obtained results suggested that, the prepared magnetic glass ceramics can be used for cancer treatment by hyperthermia and/or by localized delivery of therapeutic doses of 5-fluorouracil. - Highlights: • Preparation of magnetic glass ceramics in the system Fe{sub 2}O{sub 3} ∙ TiO{sub 2} ∙ P{sub 2}O{sub 5} ∙ SiO{sub 2} ∙ MO • The magnetic glass ceramics were tested as delivery systems for 5-fluorouracil. • Drug release profiles follow Higuchi square root of time and first order model.

  15. 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.

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

    Directory of Open Access Journals (Sweden)

    Guo X

    2011-11-01

    Full Text Available Xinming Guo1,*, Muwan Chen1,2,*, Wenzhou Feng1,*, Jiabi Liang1, Huibin Zhao1, Lin Tian1, Hui Chao3, Xuenong Zou11Orthopaedic Research institute/Department of Orthopaedic Surgery, the First Affiliated Hospital and Department of Pharmacy, the Fifth Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China; 2Interdisciplinary Nanoscience Center (iNANO, Aarhus University, Denmark; 3Ministry of Education Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry and Chemical Engineering of Sun Yat-sen University, Guangzhou, People's Republic of China *The first three authors contributed equally to this work as co-first authorAbstract: 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.Keywords: self-assembly, surface modification, tantalum, drug delivery system, doxorubicin, bone tumor

  17. Bone regenerating effect of surface-functionalized titanium implants with sustained-release characteristics of strontium in ovariectomized rats

    Directory of Open Access Journals (Sweden)

    Offermanns V

    2016-05-01

    Full Text Available Vincent Offermanns,1 Ole Zoffmann Andersen,2 Gregor Riede,1 Inge Hald Andersen,3 Klaus Pagh Almtoft,3 Søren Sørensen,3 Michael Sillassen,2 Christian Sloth Jeppesen,3 Michael Rasse,1 Morten Foss,2 Frank Kloss1 1Department of Cranio-, Maxillofacial and Oral Surgery, Medical University Innsbruck, Innsbruck, Austria; 2Interdisciplinary Nanoscience Center (iNANO, Faculty of Science and Technology, Aarhus University, Aarhus, Denmark; 3Tribology Centre, Danish Technological Institute, Aarhus, Denmark Abstract: Since strontium (Sr is known for its anabolic and anticatabolic effect on bone, research has been focused on its potential impact on osseointegration. The objective of this study was to investigate the performance of nanotopographic implants with a Sr-functionalized titanium (Ti coating (Ti–Sr–O with respect to osseointegration in osteoporotic bone. The trial was designed to examine the effect of sustained-release characteristics of Sr in poor-quality bone. Three Ti–Sr–O groups, which differed from each other in coating thickness, Sr contents, and Sr release, were examined. These were prepared by a magnetron sputtering process and compared to uncoated grade 4 Ti. Composition, morphology, and mechanical stability of the coatings were analyzed, and Sr release data were gained from in vitro washout experiments. In vivo investigation was carried out in an osteoporotic rat model and analyzed histologically, 6 weeks and 12 weeks after implantation. Median values of bone-to-implant contact and new bone formation after 6 weeks were found to be 84.7% and 54.9% (best performing Sr group as compared to 65.2% and 23.8% (grade 4 Ti reference, respectively. The 12-week observation period revealed 84.3% and 56.5% (best performing Sr group and 81.3% and 39.4% (grade 4 Ti reference, respectively, for the same measurements. The increase in new bone formation was found to correlate with the amount of Sr released in vitro. The results indicate that

  18. Development of starch-gelatin complex microspheres as sustained release delivery system

    Directory of Open Access Journals (Sweden)

    B N Vedha Hari

    2012-01-01

    Full Text Available The starch was isolated from jackfruit seeds and evaluated for its preformulation properties, like tapped density, bulk density, and particle size. The fourier transform infrared (FTIR analysis was done and compared with that of the commercially available starch which confirmed the properties. Using the various concentrations of jackfruit seed starch, the microspheres were prepared, combining with gelatin by ionotropic gelation technique. The developed microspheres were subjected to analysis of particle size, drug content, entrapment efficiency, and percentage yield. The spectral analysis confirmed the presence of drug and absence of interactions. Scanning electron microscope image showed that the particles were in spherical shape with a rough surface. The in vitro drug release in water for 12 hours proved to be in the range of 89 to 100%. The various kinetic models were applied using release data to confirm the mechanism of drug. It was concluded that the jackfruit starch-gelatin microspheres gave satisfactory results and met pharmacopieal limits.

  19. Cross-Linked Dependency of Boronic Acid-Conjugated Chitosan Nanoparticles by Diols for Sustained Insulin Release

    Directory of Open Access Journals (Sweden)

    Nabil A. Siddiqui

    2016-10-01

    Full Text Available Boronic acids have been widely investigated for their potential use as glucose sensors in glucose responsive polymeric insulin delivery systems. Interactions between cyclic diols and boronic acids, anchored to polymeric delivery systems, may result in swelling of the delivery system, releasing the drug. In this study, 4-formylphenylboronic acid conjugated chitosan was formulated into insulin containing nanoparticles via polyelectrolyte complexation. The nanoparticles had an average diameter of 140 ± 12.8 nm, polydispersity index of 0.17 ± 0.1, zeta potential of +19.1 ± 0.69 mV, encapsulation efficiency of 81% ± 1.2%, and an insulin loading capacity of 46% ± 1.8% w/w. Changes in size of the nanoparticles and release of insulin were type of sugar- and concentration-dependent. High concentration of diols resulted in a sustained release of insulin due to crosslink formation with boronic acid moieties within the nanoparticles. The formulation has potential to be developed into a self-regulated insulin delivery system for the treatment of diabetes.

  20. 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

    2015-01-01

    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. PMID:26346969

  1. 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.

  2. Bulk controlled-release fertilizers' nutrient release characteristics and sustained-release effect%块状控释肥养分释放特性及缓释效果研究

    Institute of Scientific and Technical Information of China (English)

    李慧; 陈少雄; 杜阿朋; 吴志华

    2012-01-01

    采用淋溶和水浸两种方式研究了相同原料配方的块状肥和粒状肥的NPK的释放特性及其缓释效果.用一级动力学方程,抛物线扩散方程和Elovich方程对它们释放养分的行为进行拟合,结果显示一级动力学方程对于块状肥料的拟合效果最好,其拟合度大多可达0.95以上,而Elovich方程对粒状肥料的拟合效果较好.并以浸提液中的P释放浓度为指标分阶段进行比较,结果显示不同外形设计和不同质量的肥料之间均有不同程度的差异,其中块状肥和对照组中的粒状肥之间差异显著.另外,利用拟合方程计算肥料中的P在第1天和第28天的释放率,与国标进行对比,检验所有肥料的缓释性,实验结果显示缓释性均达到国标要求.其中无孔块状肥料相对于粒状肥料在第1天和第28天的溶出率分别减少了46.02%和6.30%,有孔块状肥料相对粒状肥料分别减少了36.92%和10.92%,缓释效果显著.结合苗木需肥的实际情况,在本研究中,最终选六号肥为最佳肥料.%The leaching and extracting methods and were used to study NPK releasing characteristics and their sustained-release properties of bulk fertilizer and granular fertilizer, which were made of the same raw materials. The kinetic equation, Parabolic diffusion equation and Elovich equation were used to fit the element releasing processes. The results show the kinetic equation was the best one for matching the bulk fertilizer, its degree of fitting was more than 0.95, and the Elovich equation was more suitable for matching the granular fertilizer. Meanwhile, the release concentrations of P in different stages weere compared, the outcomes were that the fertilizers with different shape and quality had differences, the bulk fertilizer and the granular fertilizer in control group were significant different. In addition, the fitted equations of P were used to calculate the releasing rate of different fertilizer on the 1st

  3. RP-HPLC法测定格列吡嗪缓释片的释放度%RP-HPLC determination of drug release of glipizide sustained release tablets

    Institute of Scientific and Technical Information of China (English)

    屠思远; 蒋海松; 朱德志; 王建明

    2012-01-01

    建立了高效液相色谱法测定格列吡嗪缓释片的释放度.采用反相高效液相色谱法.固定相为ODS C18色谱柱(5μm,4.6 mm×250 mm)以0.1 mol/L磷酸二氢钠溶液(用2 mol/L氢氧化钠溶液调节pH值至(6.00±0.05)-甲醇(55:45)为流动相,流速为1.0 mL/min.柱温室温.检测波长为225nm.采用溶出度测定法第三法装置,以0.5%十二烷基硫酸钠溶液250 mL作为释放介质,转速为50r/min,依法操作,经2、6、10 h取样测定.当格列吡嗪在释放介质中在1.019 ~ 26.49μg/mL质量浓度范围内,峰面积与质量浓度呈良好的线性关系(r =0.999 9).证明方法结果准确,不受制剂中辅料的干扰,适用于格列吡嗪缓释片的释放度测定.%This paper established an RP - HPLC method for the determination of the drug release of glipizide sustained release tablets. The RP - HPLC was on a ODS C18 column (5 μm, 4. 6 mm × 250 mm) at room temperature, using the mobile phase of methanol - buffer solution(0. 1 mol/L sodium dihydrogen phosphate, adjusted to pH (6. 00 ±0. 05) with 2 mol/L sodium hydroxide) (55∶45) , at a flow rate of 1. 0 mL/min and the detection wavelength of 225 nm. Glipizide was detected by the apparatus Ⅲ of dissolution, using as the medium 250 mL of 0. 5% lauryl sodium sulfate solution, at 50 r/min. 5 mL sample of the medium in turn at 2, 6 and 10 h to determine following the above method. The calibration curve was linear in the range of 1. 019 ~ 26. 49 μg/mL. The method was accurate for the drug release determination of glipizide sustained release tablets. The analysis was out of interference of excipients.

  4. 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.

  5. Preparation of Sinomenine Hydrochloride Sustained Release Tablet and determination of the release rate%盐酸青藤碱缓释片的制备及其释放度测定

    Institute of Scientific and Technical Information of China (English)

    洪怡; 刘亚杰; 胡建峰

    2012-01-01

    Objective To prepare the Sinomenine Hydrochloride Sustained Release Tablet. Methods The prescription was selected by orthogonal design and the investigation index was the effect of EC, MCC and lactose to the release rate. The release rate and the release behavior were studied. Results The release rate of sustained release tablet fitted the first release eqution and the release rate for 12 h was more than 75%. Conclusion The prescription is reasonable, the technology is simple and the release effect is good.%目的 制备盐酸青藤碱缓释片.方法 采用正交设计法,考察乙基纤维素、微晶纤维素、乳糖对缓释片溶出度的影响,进行处方筛选,对最佳处方进行溶出度测定及释放行为的拟合.结果 缓释片的释放行为符合一级释放方程,12 h释放度大于75%.结论 该缓释片处方合理,工艺简单,缓释效果好.

  6. Sustained-release pramipexole in the treatment of Parkinson’s disease

    Directory of Open Access Journals (Sweden)

    Natalia Vladimirovna Fedorova

    2012-01-01

    Full Text Available Dopamine (DA receptor agonists ensure stimulation of DA receptors in the brain, by compensating for dopaminergic deficiency in Parkinson’s disease (PD. Since 1996, pramipexole has been used to treat early and extensive PD stages; its clinical efficacy has been proven in many double-blind randomized placebo-controlled and open-labeled trials. Since 2009 the European countries and the USA has used extendedrelease pramipexole (ERP that is given once daily. Its benefits are stabilized plasma drug concentrations, 24-hour action, which provides continuous dopaminergic stimulation ofpostsynaptic receptors for the prevention and therapy of already existing motor fluctuations and drug-induced dyskinesias. Once-daily dosing of ERP increases the adherence of a patient with PD to regular treatment. Two (extended- and immediate-release formulations of pramipexole differ only in the release rate for the active ingredient from the contents of a tablet. Both formulations contain the same active ingredient, have the similar profile of interacting with DA receptors, and show pharmacotherapeutic efficacy.

  7. 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.

  8. 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.

  9. The effects of sustained release metofluthrin on the biting, movement, and mortality of Aedes aegypti in a domestic setting.

    Science.gov (United States)

    Rapley, Luke P; Russell, Richard C; Montgomery, Brian L; Ritchie, Scott A

    2009-07-01

    The impact of a sustained release metofluthrin emanator and an allethrin-based mosquito coil on biting, movement and mortality of female Aedes aegypti was assessed in an apartment. In the room in which the metofluthrin emanator was activated, mosquito biting counts were reduced to zero. Metofluthrin also had a spillover effect, significantly (P metofluthrin. Indeed, a significantly (P = 0.023) greater proportion of mosquitoes were found in the treated room after exposure to metofluthrin when compared with either the coil or control treatment. Furthermore, in the room treated with metofluthrin the majority of mosquitoes died and a spillover effect into the neighboring room caused greater than one-third mortality of the mosquitoes. Metofluthrin could be used to prevent dengue transmission within a household.

  10. [The enantioselective pharmacokinetic study of desvenlafaxine sustained release tablet in Chinese healthy male volunteers after oral administration].

    Science.gov (United States)

    Chen, Yin-xia; Du, Jiang-bo; Zhang, Yi-fan; Chen, Xiao-yan; Zhong, Da-fang

    2015-04-01

    A chiral LC-MS/MS method for the simultaneous analysis of desvenlafaxine (DVS) enantiomers in human plasma was developed and applied to a pharmacokinetic study on 12 Chinese healthy volunteers. d6-Desvenlafaxine was used as internal standard (IS). Chromatographic separation was performed on the Astec Chirobiotic V chiral column (150 mm x 4.6 mm, 5 μm). The assay was linear over the concentration range of 0.500-150 ng x mL(-1) for both enantiomers (r2 > 0.99). The method was successfully applied to a stereoselective pharmacokinetic study of 100 mg desvenlafaxine sustained release tablets on 12 Chinese healthy volunteers under fasting conditions. The results showed that the pharmacokinetic parameters were similar to both enantiomers in Chinese healthy volunteers. The AUC(0-t), and C(max) of the two enantiomers were about 1.5 times higher than those of blacks and whites reported in the literature.

  11. Alginate/chitosan based bi-layer composite membrane as potential sustained-release wound dressing containing ciprofloxacin hydrochloride

    Science.gov (United States)

    Han, Fei; Dong, Yang; Song, Aihua; Yin, Ran; Li, Sanming

    2014-08-01

    The aims of this research were to develop and evaluate a novel ciprofloxacin hydrochloride loaded bi-layer composite membrane based on alginate and chitosan. In vitro antimicrobial activity, drug permeation study, morphology, cytotoxicity, primary skin irritation and in vivo pharmacodynamics were investigated. Results showed that the membranes could inhibit the growth of microorganisms for longer than 7 days. And there was no significant decrease in the metabolic activity of the Hacat fibroblasts cells were treated with the membranes. No edema and erythema were observed after administration of membranes on the rabbit skin after 14 days. Moreover, the results of pharmacodynamics showed that the membranes were more effective in improving the wound healing process. In conclusion, a novel bi-layer composite membrane was developed and results suggested that it could be exploited as sustained-release wound dressings.

  12. 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

  13. HIGH MOLECULAR CELLULOSE ESTERS. MECHANISM OF ACTION IN SUSTAINED RELEASE MATRIX TABLETS. DISSOLUTION PROFILE OF ACTIVE DRUG DEPENDING ON MOLECULAR WEIGHT AND HYDROPHILIC PROPERTIES OF POLYMERS

    Directory of Open Access Journals (Sweden)

    S. V. Trofimov

    2015-01-01

    Full Text Available This article reviews cellulose esters as important excipients in development of dosage forms with sustained release. We have studied modern methods of drug development, based on technological, and physical and chemical properties of excipients to provide a sustained release effect and the mechanism of interaction between active substance and excipients for justification of choice of the optimum prolonging agent in compliance with desirable result. Different cellulose esters were used as model excipients. They were hydroxypropylmethylcellulose (HPMC and hydroxyethylcellulose (HEC. we have studied an effect of molecular weight and hydrophilic properties on dissolution rate of active substance from the tablets with sustained release.

  14. 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.

  15. Sustained release of doxorubicin from zeolite-magnetite nanocomposites prepared by mechanical activation.

    Science.gov (United States)

    Arruebo, Manuel; Fernández-Pacheco, Rodrigo; Irusta, Silvia; Arbiol, Jordi; Ibarra, M Ricardo; Santamaría, Jesús

    2006-08-28

    Nanocomposites consisting of magnetite and FAU zeolite with a high surface area and adsorption capacity have been prepared by mechanical activation using high-energy milling at room temperature. FTIR results, as well as HRTEM, EFTEM, and XPS measurements, show that the resulting magnetic nanoparticles are covered by a thin aluminosilicate coating. A saturation magnetization as high as 16 emu g(-1) and 94.2 Oe of coercivity were observed for the obtained composites. The main advantages of this synthesis procedure are (i) simplicity of the preparation procedure, (ii) prevention of agglomeration of the magnetite nanoparticles to a large extent, and (iii) absence of free magnetite outside the zeolitic matrix. In addition, in vitro experiments revealed that the nanoparticles prepared were able to store and release substantial amounts of doxorubicin. In view of these advantages, these magnetic nanoparticles can be considered as potential candidates for drug-delivery applications.

  16. Study on dissolution in vitro of Zhike Pingchuan sustained-release tablets%止咳平喘缓释片体外释放度的研究

    Institute of Scientific and Technical Information of China (English)

    李晓燕; 冯中; 霍务贞; 李苑新; 王博; 朱盛山

    2009-01-01

    Objective:To establish a method to evaluate the in vitro release of Zhike Pingchuan sustained-release tablets.Method:The ephedrine,pseudoephedrine,scopolamine were chosen as marker components components,and the chromatographic conditions were chosen according to the separation of baseline and theoretical plate number for determining the marker in vitro release of Zhike Pingchuan sustained-release tablets;through the dissolution curves of the three active components,the release behavior was judged as well-balanced release or not.Result:Compared with conventional tablets,the Zhike Pingchuan sustained-release tablets had a well-balanced behavior in 10 h.Conclusion:The maker components of Zhike Pingchuan sustained-release tablets and two chromato-graphic conditions,which were used to determine the dissolution of the sustained-release table's,could be chosen as evaluation meth-ods for the in vitro release of Zhike Pingchuan sustained-release tablets.%目的:建立止咳平喘缓释片体外均衡释放的评价方法.方法:以麻黄碱、伪麻黄碱、东莨菪碱为指标成分,以色谱基线分离和理论塔板数考察选择止咳平喘缓释片体外释放度评价测定色谱条件;以3个指标成分的释放度曲线条件评价缓释片是否均衡释放.结果:与止咳平喘普通片相比,止咳平喘缓释片3个指标成分在10 h内成均衡释放.结论:止咳平喘缓释片释放度测定选择的3个指标成分和2个色谱条件可作为建立该缓释片均衡释放度评价方法的基础.

  17. Gradual and sustained carbon dioxide release during Aptian Oceanic Anoxic Event 1a

    Science.gov (United States)

    Naafs, B. D. A.; Castro, J. M.; de Gea, G. A.; Quijano, M. L.; Schmidt, D. N.; Pancost, R. D.

    2016-02-01

    During the Aptian Oceanic Anoxic Event 1a, about 120 million years ago, black shales were deposited in all the main ocean basins. The event was also associated with elevated sea surface temperatures and a calcification crisis in calcareous nannoplankton. These environmental changes have been attributed to variations in atmospheric CO2 concentrations, but the evolution of the carbon cycle during this event is poorly constrained. Here we present records of atmospheric CO2 concentrations across Oceanic Anoxic Event 1a derived from bulk and compound-specific δ13C from marine rock outcrops in southern Spain and Tunisia. We find that CO2 concentrations doubled in two steps during the oceanic anoxic event and remained above background values for approximately 1.5-2 million years before declining. The rise of CO2 concentrations occurred over several tens to hundreds of thousand years, and thus was unlikely to have resulted in any prolonged surface ocean acidification, suggesting that CO2 emissions were not the primary cause of the nannoplankton calcification crisis. We find that the period of elevated CO2 concentrations coincides with a shift in the oceanic osmium-isotope inventory associated with emplacement of the Ontong Java Plateau flood basalts, and conclude that sustained volcanic outgassing was the primary source of carbon dioxide during Oceanic Anoxic Event 1a.

  18. Development and characterization of sustain release gastro retentive floating microsphere of diltiazem hydrochloride for the treatment of hypertension

    Directory of Open Access Journals (Sweden)

    Mangal S Panwar

    2015-01-01

    Full Text Available Gastroretentive drug delivery systems are the systems, which are retained in the stomach for a longer period and thereby improve the bio-availability of drugs. Diltiazem hydrochloride (DTZ HCl, is a calcium channel blocker, an antihypertension and antianginal drug, DTZ HCl undergoes an extensive biotransformation, mainly through cytochrome P-450 CYP3A, which results in <4% of its oral dose being excreted unchanged in urine. Suffers from poor bio-availability (~30-40% owing to an important first pass metabolism. It has an elimination half-life of 3.5 h and an absorption zone from the upper intestinal tract. Thus, the present work is aimed to formulate sustain release floating microsphere of DTZ HCl for gastroretentive drug delivery system. Floating microsphere were prepared using nonaqueous solvent evaporation method using polycarbonate, chitosan, ethyl cellulose, hydroxypropyl methycellulose and acrycoat as materials in various quantities, in varying ratio to formulate 20 formulations of the floating microsphere. Observations of all formulations for physical characterization had shown that, all of them comply with the specification of official pharmacopoeias and/or standard reference. It was observed that microsphere of batch F3 followed the results obtained, it was concluded that the formulation 98.72% F3 is the best formulations as the extent of drug release was found to be around 99.81% at the desired time 12 h.

  19. Metabolism and pharmacokinetics of barnidipine hydrochloride, a calcium channel blocker, in man following oral administration of its sustained release formulation.

    Science.gov (United States)

    Teramura, T; Watanabe, T; Higuchi, S; Hashimoto, K

    1997-02-01

    1. The metabolism and pharmacokinetics of barnidipine hydrochloride, a 1, 4-dihydropyridine calcium antagonist were evaluated following single oral administration of a sustained release formulation (SR) capsule comprising of quick and slow release pellets to healthy male volunteers. 2. Various metabolites were identified and quantitated by newly established GC-MS analytical methods. Major metabolites were the hydrolyzed product of the benzyl-pyrrolidinyl ester (M-3) in plasma and its oxidized pyridine product (M-4) in plasma and urine. The pyridine form of unchanged barnidipine and the N-debenzylated product were observed as minor metabolites. Therefore, the primary metabolic pathways in man are (a) hydrolysis of the benzylpyrrolidine ester, (b) N-debenzylation, and (c) oxidation of the dihydropyridine ring. 3. When the SR and normal capsules were administered at a dose of 10 mg to six subjects in a crossover design, AUC 0-infinity of unchanged drug, M-3 and 4 in each subject receiving the SR were 97 +/- 15, 85 +/- 31 and 76 +/- 21% respectively of those subjects receiving the normal formulation. The sum of the excretion of urinary metabolites for the SR formulation was 65 +/- 6% of that for the normal formulation. These data suggest that the absorption of the SR formulation is slightly reduced but that its bioavailability is comparable to that of the normal formulation.

  20. Studies on the toxic effects of periodontal sustained release drug containing ornidazole and pefloxacin mesylate on early embryonic development of SD rat

    OpenAIRE

    2011-01-01

    Objective To evaluate the toxic effects of periodontal sustained release drug containing ornidazole and pefloxacin mesylate on early embryonic development of SD rats.Methods A total of 100female SD rats were randomly divided into negative control,low-,medium-,high-dose group and intervention group(20each).Rats in low-,medium-and high-dose group were fed daily with the sustained release drug at 1,4,and 8g/kg respectively;those in negative control group were fed daily with distilled water from ...

  1. Sustained release of TGFbeta3 from PLGA microspheres and its effect on early osteogenic differentiation of human mesenchymal stem cells.

    Science.gov (United States)

    Moioli, Eduardo K; Hong, Liu; Guardado, Jesse; Clark, Paul A; Mao, Jeremy J

    2006-03-01

    Despite the widespread role of transforming growth factor-beta3 (TGFbeta3) in wound healing and tissue regeneration, its long-term controlled release has not been demonstrated. Here, we report microencapsulation of TGFbeta3 in poly-d-l-lactic-co-glycolic acid (PLGA) microspheres and determine its bioactivity. The release profiles of PLGA-encapsulated TGFbeta3 with 50:50 and 75:25 PLA:PGA ratios differed throughout the experimental period. To compare sterilization modalities of microspheres, bFGF was encapsulated in 50:50 PLGA microspheres and subjected to ethylene oxide (EO) gas, radio-frequency glow discharge (RFGD), or ultraviolet (UV) light. The release of bFGF was significantly attenuated by UV light, but not significantly altered by either EO or RFGD. To verify its bioactivity, TGFbeta3 (1.35 ng/mL) was control-released to the culture of human mesenchymal stem cells (hMSC) under induced osteogenic differentiation. Alkaline phosphatase staining intensity was markedly reduced 1 week after exposing hMSC-derived osteogenic cells to TGFbeta3. This was confirmed by lower alkaline phosphatase activity (2.25 +/- 0.57 mU/mL/ng DNA) than controls (TGFbeta3- free) at 5.8 +/- 0.9 mU/mL/ng DNA (p 0.05). These findings provide baseline data for potential uses of microencapsulated TGFbeta3 in wound healing and tissue-engineering applications.

  2. 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.

  3. 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.

  4. A sustained release formulation of chitosan modified PLCL:poloxamer blend nanoparticles loaded with optical agent for animal imaging

    Energy Technology Data Exchange (ETDEWEB)

    Ranjan, Amalendu P; Zeglam, Karim; Mukerjee, Anindita; Vishwanatha, Jamboor K [Department of Molecular Biology and Immunology, University of North Texas Health Science Center, Fort Worth, TX 76107 (United States); Thamake, Sanjay, E-mail: Jamboor.vishwanatha@unthsc.edu [Department of Biomedical Sciences, University of North Texas Health Science Center, Fort Worth, TX 76107 (United States)

    2011-07-22

    The objective of this study was to develop optical imaging agent loaded biodegradable nanoparticles with indocynanine green (ICG) using chitosan modified poly(L-lactide-co-epsilon-caprolactone) (PLCL):poloxamer (Pluronic F68) blended polymer. Nanoparticles were formulated with an emulsification solvent diffusion technique using PLCL and poloxamer as blend-polymers. Polyvinyl alcohol (PVA) and chitosan were used as stabilizers. The particle size, shape and zeta potential of the formulated nanoparticles and the release kinetics of ICG from these nanoparticles were determined. Further, biodistribution of these nanoparticles was studied in mice at various time points until 24 h following intravenous administration, using a non-invasive imaging system. The average particle size of the nanoparticles was found to be 146 {+-} 3.7 to 260 {+-} 4.5 nm. The zeta potential progressively increased from - 41.6 to + 25.3 mV with increasing amounts of chitosan. Particle size and shape of the nanoparticles were studied using transmission electron microscopy (TEM) which revealed the particles to be smooth and spherical in shape. These nanoparticles were efficiently delivered to the cytoplasm of the cells, as observed in prostate and breast cancer cells using confocal laser scanning microscopy. In vitro release studies indicated sustained release of ICG from the nanoparticles over a period of seven days. Nanoparticle distribution results in mice showing improved uptake and accumulation with chitosan modified nanoparticles in various organs and slower clearance at different time points over a 24 h period as compared to unmodified nanoparticles. The successful formulation of such cationically modified nanoparticles for encapsulating optical agents may lead to a potential deep tissue imaging technique for tumor detection, diagnosis and therapy.

  5. A sustained release formulation of chitosan modified PLCL:poloxamer blend nanoparticles loaded with optical agent for animal imaging

    Science.gov (United States)

    Ranjan, Amalendu P.; Zeglam, Karim; Mukerjee, Anindita; Thamake, Sanjay; Vishwanatha, Jamboor K.

    2011-07-01

    The objective of this study was to develop optical imaging agent loaded biodegradable nanoparticles with indocynanine green (ICG) using chitosan modified poly(L-lactide-co-epsilon-caprolactone) (PLCL):poloxamer (Pluronic F68) blended polymer. Nanoparticles were formulated with an emulsification solvent diffusion technique using PLCL and poloxamer as blend-polymers. Polyvinyl alcohol (PVA) and chitosan were used as stabilizers. The particle size, shape and zeta potential of the formulated nanoparticles and the release kinetics of ICG from these nanoparticles were determined. Further, biodistribution of these nanoparticles was studied in mice at various time points until 24 h following intravenous administration, using a non-invasive imaging system. The average particle size of the nanoparticles was found to be 146 ± 3.7 to 260 ± 4.5 nm. The zeta potential progressively increased from - 41.6 to + 25.3 mV with increasing amounts of chitosan. Particle size and shape of the nanoparticles were studied using transmission electron microscopy (TEM) which revealed the particles to be smooth and spherical in shape. These nanoparticles were efficiently delivered to the cytoplasm of the cells, as observed in prostate and breast cancer cells using confocal laser scanning microscopy. In vitro release studies indicated sustained release of ICG from the nanoparticles over a period of seven days. Nanoparticle distribution results in mice showing improved uptake and accumulation with chitosan modified nanoparticles in various organs and slower clearance at different time points over a 24 h period as compared to unmodified nanoparticles. The successful formulation of such cationically modified nanoparticles for encapsulating optical agents may lead to a potential deep tissue imaging technique for tumor detection, diagnosis and therapy.

  6. Preparation and application of sustained release microcapsules of potassium ferrate(VI) for dinitro butyl phenol (DNBP) wastewater treatment

    Energy Technology Data Exchange (ETDEWEB)

    Wang Huilong, E-mail: davidwang_71@yahoo.com.cn [Department of Chemistry, Dalian University of Technology, Dalian 116023 (China); Liu Shuqin [Department of Chemistry, Dalian University of Technology, Dalian 116023 (China); Zhang Xiuyan [Dalian Fishery Technical Extension Center, Dalian 116023 (China)

    2009-09-30

    The encapsulated potassium ferrate(VI) (K{sub 2}FeO{sub 4}) samples were successfully prepared by phase separation method in organic solvents. The ethyl cellulose and paraffin were selected for the microcapsule wall materials (WM). The as prepared microcapsules were characterized by X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FT-IR). The stability can be enhanced greatly when ferrate(VI) was encapsulated in the microcapsules with a mass ratio of Fe(VI):WM in the range of 1:1-1:3 for the same conserved time in air compared for pure K{sub 2}FeO{sub 4}. The sustained release behavior of the microcapsules with different Fe(VI):WM mass ratios in 8.0 M KOH solution was also investigated. The results indicated that the Fe(VI) release was reduced with increase of Fe(VI):WM mass ratios from 1:1 to 1:3. The release kinetics of the microcapsules is found to obey Ritger-Peppas equation. The prepared Fe(VI) microcapsules has been used for the removal of a typical alkyl dinitro phenol compound, 2-sec-butyl-4,6-dinitrophenol (DNBP), from aqueous solution. The effect of pH, microcapsule concentration and reaction time was studied thoroughly. The optimal pH for DNBP degradation was 6.5, and at this pH and a microcapsule concentration of 1.2 g/L, approximately 93% of the DNBP was degraded after 80 min. The encapsulated ferrate(VI) samples were found to be very effective in the decolorization and COD reduction of real wastewater from DNBP manufacturing. Thus, this study showed the feasible and potential use of encapsulated Fe(VI) samples in degradation of various toxic organic contaminants and industrial effluents.

  7. 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.

  8. Matrix formation in sustained release tablets: possible mechanism of dose dumping.

    Science.gov (United States)

    Krajacic, Aleksandra; Tucker, Ian G

    2003-01-30

    Conditions under which poly(ethyl acrylate, methyl methacrylate) 2:1 (poly(EA-MMA), Eudragit NE) forms a stable matrix were investigated in tablets with diclofenac sodium (DS) as an active substance. DS was granulated with the aqueous polymer dispersion. Granules and/or tablets were cured under various temperature and humidity conditions. A six position rotating disk (200 rpm) apparatus was used for the release studies conducted in 37 degrees C acid then phosphate buffer (0.4 M) pH 6.8 or buffer only as the dissolution media. Morphological characteristics of the tablet surface were observed under SEM. Changes in tablet structure upon curing were evaluated through changes in tablet mechanical characteristics. Modulus of rupture, Young's modulus, AUC, AUC(max), where AUC=AUC(max), were determined by the three-point bending test. Some poorly cured tablets dose-dumped when placed directly into buffer but not if first placed in acid and then buffer. A higher content of polymer in the matrix, led to formation of a stronger polymer network upon higher curing temperature and/or longer curing duration, whereas relative humidity had a minor effect.

  9. 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

  10. Development of sustained release floating drug delivery system for norfloxacin: in vitro and in vivo evaluation.

    Science.gov (United States)

    Guguloth, Mohan; Bomma, Ramesh; Veerabrahma, Kishan

    2011-01-01

    Norfloxacin is a drug with an absorption window. Its oral bioavailability is 30-40% and is a case for improvement by appropriate formulation design. In our previous study, gastroretentive floating tablets for norfloxacin were developed employing three different polymers such as HPMC K4M, HPMC K100M, and xanthan gum. The purpose of this investigation is to further improve and evaluate the in vitro and in vivo performance of the prepared floating tablets by inclusion of citric acid as an acidifier, which is also useful in a fed state. The prepared tablets were characterized and found to exhibit satisfactory physico-chemical characteristics. The effects of citric acid at different concentrations on drug release and floating properties were studied. All the prepared batches showed good in vitro buoyancy. It was observed that the tablets remained buoyant for 24 h. The best formulation (F4c), consisting of 1.5% citric acid and 18% HPMC K4M, was selected based on in vitro characteristics and used in vivo radiographic studies by incorporating barium sulphate. These studies revealed that the tablets remained in the stomach for 205 ± 8.4 min in fasting human volunteers. In vivo studies were carried out for the best formulation in eight healthy male human volunteers, and the pharmacokinetic parameters of the developed formulation were compared with marketed conventional (Norbid) tablets. Based on the in vivo performance in a two-way, crossover study design in healthy subjects, the developed floating tablets showed superior bioavailability than the Norbid tablets. The increased bioavailability of developed formulation was found to be 16.27%. Norfloxacin is a broad-spectrum antibiotic used to treat bacterial infections such as respiratory and urinary tract infections. Conventional norfloxacin tablets show incomplete drug absorption resulting in lower bioavailabilty. Norfloxacin is better absorbed in the stomach. The dosage forms that remain in the stomach are referred to as

  11. Once daily baclofen sustained release or gastro-retentive system are acceptable alternatives to thrice daily baclofen immediate release at same daily dosage in patients

    Directory of Open Access Journals (Sweden)

    Sampat Nitin

    2009-01-01

    Full Text Available Background: Baclofen, a GABA-agonist, is currently available as an immediate release (IR formulation for relieving neurogenic spasticity in a variety of disorders. Baclofen IR requires to be administered three times a day which inadvertently increases the chances of medication noncompliance among patients and is also associated with side effects such as drowsiness and muscle weakness. Aim: To overcome the shortcomings of baclofen IR, two modified formulations, baclofen sustained release (SR and gastric retentive system (GRS, have been proposed to be equivalent in efficacy to baclofen IR with the administration of a single daily dose. Materials and Methods: Ninety patients with chronic neurogenic muscular spasticity were enrolled requiring 10-20 mg of baclofen IR every eight hours. The patients were randomized to two treatment arms: SR (n = 46 or GRS (n = 44 at the same once-daily dose for four weeks. Efficacy was measured by Ashworth score for muscle tone, spasm score, reflex score, 30-item functional independence score, and patient′s diary score for three most affected activities of daily life. Results: The mean Ashworth score changed significantly (P = 0.00 for patients in the SR group from 3.03-2.69 (-0.35 and 3.07-2.70 (-0.37 for patients in the GRS group. There was no significant difference (P = 0.87 between baseline-adjusted Ashworth score reductions on SR (-0.35 and GRS (-0.37. Similar results were obtained for spasm, reflex, and functional independence scores. The mean baseline-adjusted patient-diary scores did not differ significantly between 8 am, 12 pm, 4 pm, and 8 pm (P = 0.96, either on SR (-5.3 to -6.1 or GRS (-7.3 to -8.1, indicating a uniform effect round-the-day on both. Further, sedation scores (mean ± SEM decreased significantly (P < 0.05 on both SR (10.36 ± 1.37 to 6.18 ± 0.92 and GRS (8.14 ± 1.57 to 5.33 ± 1.11, suggesting better toleration. Conclusion: Once-daily baclofen SR and GRS are efficacious, convenient, and

  12. 富马酸喹硫平缓释片在不同释放介质中的体外释放研究%Drug Release of Quetiapine Fumarate Sustained-release Tablets in Different Release Mediums in vitro

    Institute of Scientific and Technical Information of China (English)

    杨大龙; 杨意波; 卢定强; 谢浩; 严相平

    2013-01-01

    OBJECTIVE: To investigate release behavior of Quetiapine fumarate sustained-release tablets in vitro and its mechanism. METHODS: Taking foreign prepaf ations in the market as control, the similarity of release behavior of 2 preparations in 3 medium (water, 0.1 mol/L hydrochloric acid, pH 6.8 phosphate buffer solution) were analyzed with basket method. The release rates of them were determined by UV spectrophotometry, and similarity factor f2 was used to evaluate the similarity of release curves. Release behavior model was fitted for self-made preparation. RESULTS: In 3 kinds of mediums, similarity factor f2 of 2 preparations was more than 50; in vitro drug release of self-made preparation was consistent with Higuchi equation and Peppas equation in water and pH 6.8 phosphate buffer, and more consistent with first-order equation and Peppas equation in 0.1 mol/L hydrochloric acid. CONCLUSIONS: The release behavior of self-made preparation and reference preparation are similar in different release mediums, and the release mechanism is mainly diffusion mode.%目的:考察自制富马酸喹硫平缓释片的体外释放情况及其释放机制.方法:以国外上市制剂为参比,采用篮法进行2种制剂分别在3种释放介质(水、0.1 mol/L盐酸溶液、pH 6.8磷酸盐缓冲液)中体外释放行为的相似性比较;采用紫外分光光度法测定释放度,以相似因子(f2)进行相似度评价;并对自制制剂进行释放行为模型的拟合.结果:在3种释放介质中,2种制剂比较,f2值均大于50;自制制剂在水和pH 6.8磷酸盐缓冲液中体外释放拟合模型更接近Higuchi方程和Peppas方程,在0.1 mol/L盐酸溶液中更接近一级方程和Peppas方程.结论:自制制剂与参比制剂在不同释放介质中的体外释放行为一致,释放机制以扩散为主.

  13. 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

    Tuberculosis, a highly contagious disease, ranks as the second leading cause of death from an infectious disease, and remains a major global health problem. In 2013, 9 million new cases were diagnosed and 1.5 million people died worldwide from tuberculosis. This dissertation aims at developing a new, ultrafine particle-based efficient antibiotic delivery system for the treatment of tuberculosis. The carrier material to make the rifampicin (RIF)-loaded particles is a low molecular weight star-shaped polymer produced from glucosamine (molecular core building unit) and L-lactide (GluN-LLA). Stable particles with a very high 50% drug loading capacity were made via electrohydrodynamic atomization. Prolonged release (>14 days) of RIF from these particles is demonstrated. Drug release data fits the Korsmeyer-Peppas equation, which suggests the occurrence of a modified diffusion-controlled RIF release mechanism, and is also supported by differential scanning calorimetry and drug leaching tests. Cytotoxicity tests on Mycobacterium smegmatis showed that antibiotic-free GluN-LLA and polylactides (PLA) (reference material) particles did not show any significant anti-bacterial activity. The minimum inhibitory concentration and minimum bactericidal concentration values obtained for RIF-loaded particles showed 2- to 4-fold improvements in the anti-bacterial activity relative to the free drug. Cytotoxicity tests on macrophages indicated an increment in cell death as particle dose increased, but was not significantly affected by material type or particle size. Confocal microscopy was used to track internalization and localization of particles in the macrophages. GluN-LLA particles led to higher uptakes than the PLA particles. In addition, after phagocytosis, the GluN-LLA particles stayed in the cytoplasm and the particles showed a favorable long term drug release effect in killing intracellular bacteria compared to free RIF. The studies presented and discussed in this dissertation

  14. Application of 5-Fluorouracil-Polycaprolactone Sustained-Release Film in Ahmed Glaucoma Valve Implantation Inhibits Postoperative Bleb Scarring in Rabbit Eyes.

    Science.gov (United States)

    Bi, Xiu-Zeng; Pan, Wei-Hua; Yu, Xin-Ping; Song, Zong-Ming; Ren, Zeng-Jin; Sun, Min; Li, Cong-Hui; Nan, Kai-Hui

    2015-01-01

    This study was designed to investigate whether 5-fluorouracil (5-Fu)-polycaprolactone sustained-release film in Ahmed glaucoma valve implantation inhibits postoperative bleb scarring in rabbit eyes. Eighteen New Zealand white rabbits were randomly divided into three groups (A, B and C; n = 6 per group). Group A received combined 5-Fu-polycaprolactone sustained-release film application and Ahmed glaucoma valve implantation, group B received local infiltration of 5-Fu and Ahmed glaucoma valve implantation, and group C received Ahmed glaucoma valve implantation. Postoperative observations were made of the anterior segment, intraocular pressure, central anterior chamber depth, blebs, drainage tube, and accompanying ciliary body detachment. The pathology of the blebs and surrounding tissues were observed at month 3 postoperatively. We revealed that the 5-Fu-polycaprolactone sustained-release film maintained a release concentration range of 13.7 ± 0.12 to 37.41 ± 0.47 μg/ml over three months in vitro. Postoperatively, diffuse blebs with ridges were found in all eyes in group A, two blebs were observed in group B, and no bleb formation was present in group C. The postoperative central anterior chamber depth in group A was significantly less than that of the other two groups. The postoperative intraocular pressure of group A stabilized at 6.33-8.67 mmHg, whereas that of group C gradually remained at 7.55-10.02 mmHg. The histopathology showed that the fibrous tissue thickness of the blebs in group A was significantly thinner than that of the other groups. We conclude that the 5-Fu-polycaprolactone sustained-release film had a sustained drug release effect, which promoted the inhibition of bleb scarring after Ahmed glaucoma valve implantation.

  15. Thermosensitive chitosan-based hydrogels for sustained release of ferulic acid on corneal wound healing.

    Science.gov (United States)

    Tsai, Ching-Yao; Woung, Lin-Chung; Yen, Jiin-Cherng; Tseng, Po-Chen; Chiou, Shih-Hwa; Sung, Yen-Jen; Liu, Kuan-Ting; Cheng, Yung-Hsin

    2016-01-01

    Oxidative damage to cornea can be induced by alkaline chemical burn which may cause vision loss or blindness. Recent studies showed that exogenous application of natural antioxidants may be a potential treatment for corneal wound healing. However, low ocular bioavailability and short residence time are the limiting factors of topically administered antioxidants. Ferulic acid (FA) is a natural phenolic compound and an excellent antioxidant. The study was aimed to investigate the effects of FA in corneal epithelial cells (CECs) under oxidative stress and evaluate the feasibility of use the thermosensitive chitosan-based hydrogel containing FA for corneal wound healing. The results demonstrated that post-treatment of FA on CECs could decrease the inflammation-level and apoptosis. In the rabbit corneal alkali burn model, post-treatment FA-loaded hydrogel may promote the corneal wound healing. The results of study suggest that FA-loaded hydrogel may have the potential applications in treating corneal alkali burn.

  16. Fine granules showing sustained drug release prepared by high-shear melt granulation using triglycerin full behenate and milled microcrystalline cellulose.

    Science.gov (United States)

    Aoki, Hajime; Iwao, Yasunori; Uchimoto, Takeaki; Noguchi, Shuji; Kajihara, Ryusuke; Takahashi, Kana; Ishida, Masayuki; Terada, Yasuko; Suzuki, Yoshio; Itai, Shigeru

    2015-01-30

    This study aimed to prepare fine granules with a diameter less than 200μm and sustained drug release properties by melt granulation. Triglycerin full behenate (TR-FB) was examined as a new meltable binder (MB) by comparison of its properties with those of glycerin monostearate (GM), widely used as MB. The effect of milling microcrystalline cellulose (MCC), an excipient for melt granulation, on the granule properties was also investigated. TR-FB was more stable during heating and storage than GM, and produced smaller granules with narrower particle size distribution, larger yield in the 106-200μm range, uniform roundness and better sustained drug release profile than those prepared with GM. Granules prepared with milled MCC had almost the same physicochemical properties as those produced with intact MCC. However, milled MCC produced granules with a more rigid structure and smaller void space than intact MCC. Consequently, the granules produced with milled MCC showed better sustained drug release behavior than those prepared with intact MCC. We successfully prepared fine granules with sustained drug release properties and diameter of less than 200μm using TR-FB and milled MCC. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Three-dimensional Printed Scaffolds with Gelatin and Platelets Enhance In vitro Preosteoblast Growth Behavior and the Sustained-release Effect of Growth Factors

    Directory of Open Access Journals (Sweden)

    Wei Zhu

    2016-01-01

    Conclusions: Our experiments confirmed that the 3D printed scaffolds we had designed could provide a sustained-release effect for growth factors and improve the proliferation of preosteoblasts with little cytotoxicity in vitro. They may hold promise as bone graft substitute materials in the future.

  18. Release Mechanism and Pharmaceutical Care of Oral Sustained/Controlled Release Preparations in Clinical Application%临床常用口服缓控释制剂的释药原理与服用要点

    Institute of Scientific and Technical Information of China (English)

    钱卿; 谢云芬

    2011-01-01

    缓控释药物在现今临床使用上已日趋广泛,也是药物制剂学研究的热点内容.本文简要地介绍了缓控释制剂的释药原理,并列举了常用的缓控释药品及正确的使用方法,为临床工作者合理应用提供了必要的依据.%With the increasing application in modern clinical therapy, the sustained/controlled release drug delivery systems (DDSs) are the hot spot and main trend of pharmaceutic research. The release characteristics and mechanisms for oral sustained/controlled release preparations are discussed, and those commonly used in the hospitals are introduced in this article. Providing rational administration of the drugs and strengthening pharmaceutical care is critical to ensure their safe and effective application.

  19. The preparation and evaluation of sustained release suppositories containing ketoprofen and Eudragit RL 100 by using factorial design.

    Science.gov (United States)

    Ozgüney, I; Ozcan, I; Ertan, G; Güneri, T

    2007-01-01

    The preparation of ketoprofen (KP) sustained release (SR) suppositories was designed according to the 3(2) x 2(1) factorial design as three different KP:Eudragit RL 100 ratios (1:0.5, 1:1, 1:2), three particle sizes of prepared granules (250-500, 500-710, and 710-1000 microm) and two different PEG 400:PEG 6000 ratios (40:60, 50:50). The conventional KP suppositories were also prepared by using Witepsol H 15, Massa Estarinum B, Cremao and the mixture of PEG 400:PEG 6000. The dissolution studies of suppositories prepared were carried out according to the USP XXIII basket method in the phosphate buffer (pH = 7.2) at 50 rpm, and it was shown that the dissolution time was sustained up to 8 hours. According to the results of the factorial design, the most important independent variable on t50 and t80 was drug:polymer ratios. The log of partition coefficient of KP was determined as 1.46, showing the high affinity to the oily phase. n exponent and kinetic studies were conducted to explain diffusion mechanism, and it is understood that if the inert KP:Eudragit RL 100 ratio is increased in the particles, the Fickian difusion dominates and the best kinetic turns to Higuchi from the Hixson-Crowell. There is neither crystalline form of KP nor degradation product in the suppositories detected with the differential scanning calorimetry (DSC) studies. In addition to these studies, antiinflammatory activity of SR suppositories also determined that it was significantly extended according to the conventional suppositories.

  20. Evaluation of Plantago major L. seed mucilage as a rate controlling matrix for sustained release of propranolol hydrochloride.

    Science.gov (United States)

    Saeedi, Majid; Morteza-Semnani, Katayoun; Sagheb-Doust, Mehdi

    2013-03-01

    Polysaccharide mucilage derived from the seeds of Plantago major L. (family Plantaginaceae) was investigated for use in matrix formulations containing propranolol hydrochloride. HPMC K4M and tragacanth were used as standards for comparison. The hardness, tensile strength, and friability of tablets increased as the concentration of mucilage increased, indicating good compactibility of mucilage powders. The rate of release of propranolol hydrochloride from P. major mucilage matrices was mainly controlled by the drug/mucilage ratio. Formulations containing P. major mucilage were found to exhibit a release rate comparable to HPMC containing matrices at a lower drug/polymer ratio (drug/HPMC 2:1). These results demonstrated that P. major mucilage is a better release retardant compared to tragacanth at an equivalent content. The results of kinetic analysis showed that in F3 (containing 1:2 drug/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. The DSC and FT-IR studies showed that no formation of complex between the drug and mucilage or changes in crystallinity of the drug had occurred.

  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.

  2. What Happens After the Demonstration Phase? The Sustainability of Canada's At Home/Chez Soi Housing First Programs for Homeless Persons with Mental Illness.

    Science.gov (United States)

    Nelson, Geoffrey; Caplan, Rachel; MacLeod, Timothy; Macnaughton, Eric; Cherner, Rebecca; Aubry, Tim; Méthot, Christian; Latimer, Eric; Piat, Myra; Plenert, Erin; McCullough, Scott; Zell, Sarah; Patterson, Michelle; Stergiopoulos, Vicky; Goering, Paula

    2017-03-01

    This research examined the sustainability of Canada's At Home/Chez Soi Housing First (HF) programs for homeless persons with mental illness 2 years after the end of the demonstration phase of a large (more than 2000 participants enrolled), five-site, randomized controlled trial. Qualitative interviews were conducted with 142 participants (key informants, HF staff, and persons with lived experience) to understand sustainability outcomes and factors that influenced those outcomes. Also, a self-report HF fidelity measure was completed for nine HF programs that continued after the demonstration project. A cross-site analysis was performed, using the five sites as case studies. The findings revealed that nine of the 12 HF programs (75%) were sustained, and that seven of the nine programs reported a high level of fidelity (achieving an overall score of 3.5 or higher on a 4-point scale). The sites varied in terms of the level of systems integration and expansion of HF that were achieved. Factors that promoted or impeded sustainability were observed at multiple ecological levels: broad contextual (i.e., dissemination of research evidence, the policy context), community (i.e., partnerships, the presence of HF champions), organizational (i.e., leadership, ongoing training, and technical assistance), and individual (i.e., staff turnover, changes, and capacity). The findings are discussed in terms of the implementation science literature and their implications for how evidence-based programs like HF can be sustained.

  3. An assessment of the pharmacokinetics of a sustained-release formulation of a tramadol/acetaminophen combination in healthy subjects.

    Science.gov (United States)

    Im, Yong-Jin; Jeon, Ji-Young; Kim, Eun-Young; Kim, Yunjeong; Oh, Dong-Joon; Yoo, Ji-Seok; Shin, Dae-Hee; Chae, Soo-Wan; Kim, Min-Gul

    2015-02-01

    To provide consistent pain relief and improve convenient sustained release (SR), a fixed-dose combination tramadol/acetaminophen tablet was formulated. This study aimed to evaluate the pharmacokinetic profiles of an SR 75-mg tramadol/650-mg acetaminophen formulation after a single dose compared with an immediate release (IR) 37.5-mg tramadol/325-mg acetaminophen formulation after 2 doses and at steady state and to assess the effect of food on the pharmacokinetic SR formulation profile after a single dose. Two clinical trials were conducted: (1) an open-label, randomized, 3-period, 3-treatment, crossover study to assess the pharmacokinetic SR (one 75-mg tramadol/650-mg acetaminophen combination tablet) formulation profiles after a single dose and IR (one 37.5-mg tramadol/325-mg acetaminophen combination tablet q6h for 2 doses) formulation profiles after 2 doses and the effect of food intake on healthy male subjects and (2) an open, randomized, 2-period, 2-treatment multiple dose crossover study to evaluate the steady-state pharmacokinetic SR and IR formulation profiles. Safety assessments were performed. Forty-three subjects completed each study protocol. The SR combination tramadol/acetaminophen formulation was clinically and statistically equivalent to the IR combination formulation in the fasting state. When tramadol and acetaminophen tablets were administered with food, the time to peak plasma concentrations and the tramadol/acetaminophen absorption were unaffected. There was no serious adverse event reported. The SR combination tramadol/acetaminophen tablet exhibited similar exposure and absorption rates compared with those of the IR formulation of tramadol, O-desmethyltramadol, and acetaminophen. The SR formulation may be more convenient for patients and has the potential to enhance compliance and pain control. ClinicalTrials.gov identifier: NCT01880125. Copyright © 2015 Elsevier HS Journals, Inc. All rights reserved.

  4. Study on Preparation of Cefradine Sustain-release Tablet%头孢拉定缓释制剂的制备及释放特征研究

    Institute of Scientific and Technical Information of China (English)

    虢红梅; 杨建林

    2015-01-01

    目的:头孢拉定为第1代半合成头孢菌素,为了满足临床特殊用途,进行缓释片的研究。方法采用羟丙甲纤维素(HPMC)、丙烯酸树脂Ⅱ号等缓释材料制备头孢拉定缓释制剂,并考察丙烯酸树脂Ⅱ号含量、剂型、释放介质等对体外累积释放率的影响。结果头孢拉定缓释片体外释药测定结果符合缓释制剂要求。结论头孢拉定缓释片与Higuchi方程拟合较好(在PH=1.2人工胃液中线性回归系数为0.9887,在PH=7.4人工肠液中为0.9935),是骨架溶蚀和药物扩散的综合效应过程。%Objective Cefradine is the first generation of half synthetic cePhalosPorin. To study the cefradine sustain-release tablet for sPecific usage in the clinic. Methods Sustained-release materials,such as HPMC and Eudragit Ⅱwere adoPted to PrePare the cefra-dine sustained-release dosage forms,and the effects of acrylic resin content,dosage forms and release medium on the cumulative drug release were studied. Results The cefradine sustained-release tablets met the requirements of sustained-release. Conclusion The cefradine sustained-release tablets fit well with the Higuchi equation ( PH=1. 2,R2=0. 988 7,PH=7. 4,R2=0. 994 3 ) ,which is a comPrehensive Process of skeleton dissolution and drug diffusion.

  5. The synergistic effect of nanotopography and sustained dual release of hydrophobic and hydrophilic neurotrophic factors on human mesenchymal stem cell neuronal lineage commitment.

    Science.gov (United States)

    Teo, Benjamin Kim Kiat; Tan, Guo-Dong Sean; Yim, Evelyn K F

    2014-08-01

    A combination of nanotopography and controlled release is a potential platform for neuronal tissue engineering applications. Previous studies showed that combining both physical and chemical guidance was more effective than individual cues in the directional promotion of neurite outgrowth. Nanotopography can direct human mesenchymal stem cells (hMSCs) into neuronal lineage, while controlled release of neurotrophic factors can deliver temporally controlled biochemical signals. Hypothesizing that the synergistic effect will enhance neuronal lineage commitment of hMSCs, a fabrication method for multiple neurotrophic factors delivery from a single nanopatterned (350 nm gratings), poly-ɛ-caprolactone (PCL) film was developed and evaluated. Our results showed a synergistic effect on hMSC differentiation cultured on substrates with both nanotopographical and biochemical cues. The protein/drug encapsulation into PCL nanopatterned films was first optimized using a hydrophilic model protein, bovine serum albumin. The hydrophobic retinoic acid (RA) molecule was directly incorporated into PCL films. To achieve sustained release, hydrophilic nerve growth factor (NGF) was first encapsulated within polyelectrolyte complexation fibers before they were embedded within the nanopatterned PCL film. Our results showed that nanotopography on the fabricated polymer films remained intact, while release of bioactive RA and NGF was sustained over a period of 3 weeks. Under the combinatorial effect of physical and biochemical cues, we observed an enhanced upregulation of neuronal genes such as microtubule-associated protein 2 (MAP2) and neurofilament light (NFL) as compared with sustained delivery of individual cues and bolus delivery. Quantitative polymerase chain reaction analysis showed that MAP2 and NFL gene upregulation in hMSCs was most pronounced on the nanogratings with sustained release of both RA and NGF. The fabricated platforms supported the sustained delivery of multiple

  6. Development and evaluation of sustained-release ibuprofen-wax microspheres. I. Effect of formulation variables on physical characteristics.

    Science.gov (United States)

    Adeyeye, C M; Price, J C

    1991-11-01

    A congealable disperse phase encapsulation method was used to prepare sustained-release ibuprofen-wax microspheres. Microspheres prepared with paraffin wax, such as ceresine and microcrystalline waxes, using polyvinylpyrrolidone (PVP) as dispersant had a tendency to aggregate, but the addition of wax modifiers (stearyl alcohol and glyceryl monostearate) greatly reduced aggregation. Optimum modifier and dispersant concentrations were 20% (w/w) and 5% (w/v), respectively. The particle size distribution of the microspheres was log-normal. An increase in modifier, dispersant concentration, emulsification stirring speed, or temperature shifted the size distribution toward finer particles. Microcrystalline wax required a higher emulsification temperature and produced finer particles than ozokerite wax. The recovery of drug from the different microsphere formulations varied between 71 and 92%. Differential scanning calorimetry (DSC) of the single components and physical mixtures showed endothermic peaks at the respective melting-point ranges. The DSC of the ceresine and microcrystalline wax microspheres was similar to rescans of ternary mixtures of components of the microspheres with less prominent and lower melting temperatures than individual components or physical mixtures.

  7. Repair effect of diabetic ulcers with recombinant human epidermal growth factor loaded by sustained-release microspheres

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    In this study the w/o/w extraction–evaporation technique was adopted to prepare poly(lactic-co-glycolic acid) (PLGA) microspheres loading recombinant human epidermal growth factor (rhEGF). The micro-spheres were characterized for morphology by transmission electron microscopy (TEM) and particle size distribution. The release performances, the proliferation effects and therapeutic effects of rhEGF-loaded PLGA microspheres were all studied. The results showed that these spherical micro-spheres had a narrow size distribution and a high drug encapsulation efficiency (85.6%). RhEGF-loaded microspheres enhanced the growth rate of fibroblasts and wound healing more efficiently than pure rhEGF. The number of the proliferating cell nuclear antigen (PCNA) in the epidermis layer with the mi-crosphere treatment was significantly larger than those of the control groups. Overall locally sustained delivery of rhEGF from biodegradable PLGA microspheres may serve as a novel therapeutic strategy for diabetic ulcer repair.

  8. [The effect of pretreatment with ranitidine on the pharmacokinetics and gastrointestinal transit of a sustained-release theophylline preparation].

    Science.gov (United States)

    Wilson, C G; Washington, N; Greaves, J L; Blackshaw, P E; Perkins, A C; Barkworth, M F; Rehm, K D

    1998-05-01

    A scintigraphic and pharmacokinetic study of the behavior of Bronchoretard forte (theophylline, CAS 58-55-9) was carried out in 8 healthy male volunteers to evaluate the sensitivity of the preparation to changes in gastric pH. The volunteers were pretreated with ranitidine (CAS 66357-35-5) (150 mg b.i.d.) or placebo for three days prior to and on the study day to reduce gastric acidity. The effect of the pretreatment with ranitidine on gastric pH was measured on the day before study begin and the mean pH was significantly increased compared to the placebo (ranitidine pH 2.2 +/- 2.4; placebo pH 1.6 +/- 2.0, p formulation. No significant differences were found in the gastrointestinal transit of the labelled microparticulates between the data obtained from the group treated with ranitidine and that from the placebo group. Plasma theophylline concentration profiles were identical for the two treatments. These data indicate that the theophylline sustained release formulation is not sensitive to the effects of major changes in gastric H+ concentration.

  9. 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.

  10. Repair effect of diabetic ulcers with recombinant human epidermal growth factor loaded by sustained-release microspheres

    Institute of Scientific and Technical Information of China (English)

    DONG XiaoQing; XU Jun; WANG WeiCai; Luo Hao; LIANG XiaoFei; Zhang Lei; Wang HanJie; Wang PengHua; CHANG Jin

    2008-01-01

    In this study the w/o/w extraction-evaporation technique was adopted to prepare poly(lactic-co-glycolic acid) (PLGA) microspheres loading recombinant human epidermal growth factor (rhEGF). The micro-spheres were characterized for morphology by transmission electron microscopy (TEM) and particle size distribution. The release performances, the proliferation effects and therapeutic effects of rhEGF-Ioaded PLGA microspheres were all studied. The results showed that these spherical micro-spheres had a narrow size distribution and a high drug encapsulation efficiency (85.6%). RhEGF-ioaded microspheres enhanced the growth rate of fibroblasts and wound healing more efficiently than pure rhEGF. The number of the proliferating cell nuclear antigen (PCNA) in the epidermis layer with the mi-crosphere treatment was significantly larger than those of the control groups. Overall locally sustained delivery of rhEGF from biodegradable PLGA microspheres may serve as a novel therapeutic strategy for diabetic ulcer repair.

  11. Response surface methodology and process optimization of sustained release pellets using Taguchi orthogonal array design and central composite design

    Directory of Open Access Journals (Sweden)

    Gurinder Singh

    2012-01-01

    Full Text Available Furosemide is a powerful diuretic and antihypertensive drug which has low bioavailability due to hepatic first pass metabolism and has a short half-life of 2 hours. To overcome the above drawback, the present study was carried out to formulate and evaluate sustained release (SR pellets of furosemide for oral administration prepared by extrusion/spheronization. Drug Coat L-100 was used within the pellet core along with microcrystalline cellulose as the diluent and concentration of selected binder was optimized to be 1.2%. The formulation was prepared with drug to polymer ratio 1:3. It was optimized using Design of Experiments by employing a 3 2 central composite design that was used to systematically optimize the process parameters combined with response surface methodology. Dissolution studies were carried out with USP apparatus Type I (basket type in both simulated gastric and intestinal pH. The statistical technique, i.e., the two-tailed paired t test and one-way ANOVA of in vitro data has proposed that there was very significant ( P≤0.05 difference in dissolution profile of furosemide SR pellets when compared with pure drug and commercial product. Validation of the process optimization study indicated an extremely high degree of prognostic ability. The study effectively undertook the development of optimized process parameters of pelletization of furosemide pellets with tremendous SR characteristics.

  12. Response surface methodology and process optimization of sustained release pellets using Taguchi orthogonal array design and central composite design.

    Science.gov (United States)

    Singh, Gurinder; Pai, Roopa S; Devi, V Kusum

    2012-01-01

    Furosemide is a powerful diuretic and antihypertensive drug which has low bioavailability due to hepatic first pass metabolism and has a short half-life of 2 hours. To overcome the above drawback, the present study was carried out to formulate and evaluate sustained release (SR) pellets of furosemide for oral administration prepared by extrusion/spheronization. Drug Coat L-100 was used within the pellet core along with microcrystalline cellulose as the diluent and concentration of selected binder was optimized to be 1.2%. The formulation was prepared with drug to polymer ratio 1:3. It was optimized using Design of Experiments by employing a 3(2) central composite design that was used to systematically optimize the process parameters combined with response surface methodology. Dissolution studies were carried out with USP apparatus Type I (basket type) in both simulated gastric and intestinal pH. The statistical technique, i.e., the two-tailed paired t test and one-way ANOVA of in vitro data has proposed that there was very significant (P≤0.05) difference in dissolution profile of furosemide SR pellets when compared with pure drug and commercial product. Validation of the process optimization study indicated an extremely high degree of prognostic ability. The study effectively undertook the development of optimized process parameters of pelletization of furosemide pellets with tremendous SR characteristics.

  13. Repetitive loading damages healing ligaments more than sustained loading demonstrated by reduction in modulus and residual strength.

    Science.gov (United States)

    Thornton, Gail M; Bailey, Soraya J

    2012-10-11

    Healing ligaments have decreased strength compared to normal ligaments, leaving healing ligaments vulnerable to damage accumulation during normal daily activities at functional stresses. Rabbit medial collateral ligament gap scars after 14 weeks of healing were exposed to long-term creep and fatigue loading over a range of functional stresses. In addition to the 58 healing ligaments that underwent in vitro creep and fatigue testing, seven healing ligaments underwent only monotonic failure tests for comparison with residual strength tests that followed creep and fatigue testing. When exposed to repetitive loading during fatigue testing, healing ligaments exhibited modulus reduction earlier than when exposed to sustained loading during creep testing that was occasionally interrupted with unloading/reloading cycles to measure modulus. In other words, after the same loading duration, repetitive loading was more damaging than sustained loading. At modulus reduction, the increase in strain during fatigue was greater than or similar to that during creep. Healing ligaments that were damaged during long-term loading exhibited decreased strength and increased toe-region strain during subsequent residual strength tests. Normal daily activities that result in repetitive loading of a ligament healing from an injury will likely cause damage to accumulate faster than activities that result in sustained loading.

  14. 熔融制粒法制备盐酸二甲双胍缓释片%Preparation of Metformin Hydrochloride Sustained-release Tablets By Melt Granulation

    Institute of Scientific and Technical Information of China (English)

    许谙; 孙丹青

    2013-01-01

    OBJECTIVE To prepare metformin hydrochloride sustained-release tablets and to study its release characterization in vitro and the factors affecting drug release.METHODS Metformin hydrochloride sustained-release tablets were prepared with glycery behenate as matrix material,microcrystalline cellulose as pore-forming agent by melt granulation.The impacts of releasing transmitter,contents of glycery behenate and microcrystalline cellulose,and preparation process factors on the drug release in vitro of the tablets were studied.RESULTS The contents of glycery behenate and microcrystalline cellulose were critical factors affecting drug release rate.The tablets had a remarkable sustained-release property,the drug release profile in vitro followed zero order or Higuchi kinetics.CONCLUSION Using glycery behenate as the wax matrix material,combining with other filers,a sustained release tablet of once daily administration is prepared by melt granulation.%目的 制备盐酸二甲双胍缓释片,并考察其释药行为及影响因素.方法 以山嵛酸甘油酯为骨架材料,微晶纤维素为致孔剂,采用熔融制粒技术制备盐酸二甲双胍缓释片,并考察不同释放介质,山嵛酸甘油酯、微晶纤维素的不同用量以及制备工艺参数等对该缓释片体外释放的影响.结果 山嵛酸甘油酯和微晶纤维素的用量为药物释放的主要影响因素,制备的缓释片具有明显的缓释特征,体外释药过程符合零级动力学模型.结论 采用山嵛酸甘油酯作为蜡质骨架材料,结合其他辅料,采用熔融制粒技术可制备日服1次的盐酸二甲双胍缓释片.

  15. Preparation and in vitro release of ketoprofen sustained-release pellet tablets%酮洛芬微丸缓释片的制备及体外释放度考察

    Institute of Scientific and Technical Information of China (English)

    李海刚; 袁中文; 关世侠; 周郁斌; 胡波; 叶小玲; 杨艳

    2011-01-01

    目的:制备一种酮洛芬缓释片剂.方法:采用挤出-滚圆法制备酮洛芬微丸,用Eudragit(R) RS 30D和Eudragit(R) RL30D包衣.再将包衣微丸与酮洛芬原药压片,最终制成酮洛芬缓释片.结果:体外释放度实验显示,制备的酮洛芬缓释片在2h内能释药30%,剩余70%药物在随后的10h内缓慢释放.结论:用本方法制备酮洛芬缓释片,工艺简便,易于操作.%OBJECTIVE To prepare detoprofen sustained-release tablets. METHODS Extrusion-spheronization technique was introduced to prepare ketoprofen pellets and Eudragir? RS 30D and Eudragit? RL 30D were used as coating materials. Even mix the coated pellets with ketoprofen to prepare ketoprofen sustained-release tablets. RESULTS The data obtained proved that the formulation was useful for a sustained-release of ketoprofen, due to the percentage released in two hours was 30% and in the later ten hours was 70%. CONCLUSION The preparation technology is reliable and easy to operate.

  16. 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

  17. Investigation of in situ gelling alginate formulations as a sustained release vehicle for co-precipitates of dextromethrophan and Eudragit S 100.

    Science.gov (United States)

    El Maghraby, Gamal Mohamed; Elzayat, Ehab Mostafa; Alanazi, Fars Kaed

    2014-03-01

    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.

  18. Properties of gastroretentive sustained release tablets prepared by combination of melt/sublimation actions of L-menthol and penetration of molten polymers into tablets.

    Science.gov (United States)

    Fukuda, Mamoru; Goto, Akinori

    2011-01-01

    A novel floating sustained release tablet having a cavity in the center was developed by utilizing the physicochemical properties of L-menthol and the penetration of molten hydrophobic polymer into tablets. A dry-coated tablet containing famotidine as a model drug in outer layer was prepared with a L-menthol core by direct compression. The tablet was placed in an oven at 80°C to remove the L-menthol core from tablet. The resulting tablet was then immersed in the molten hydrophobic polymers at 90°C. The buoyancy and drug release properties of tablets were investigated using United States Pharmacopeia (USP) 32 Apparatus 2 (paddle 100 rpm) and 900 ml of 0.01 N HCl. The L-menthol core in tablets disappeared completely through pathways in the outer layer with no drug outflows when placed in an oven for 90 min, resulting in a formation of a hollow tablet. The hollow tablets floated on the dissolution media for a short time and the drug release was rapid due to the disintegration of tablet. When the hollow tablets were immersed in molten hydrophobic polymers for 1 min, the rapid drug release was drastically retarded due to a formation of wax matrices within the shell of tablets and the tablets floated on the media for at least 6 h. When Lubri wax® was used as a polymer, the tablets showed the slowest sustained release. On the other hand, faster sustained release properties were obtained by using glyceryl monostearate (GMS) due to its low hydrophobic nature. The results obtained in this study suggested that the drug release rate from floating tablets could be controlled by both the choice of hydrophobic polymer and the combined use of hydrophobic polymers.

  19. Study on the sustained-release profile of nano selenium chitosan composite%纳米硒-壳聚糖复合物缓释作用研究

    Institute of Scientific and Technical Information of China (English)

    吴永军

    2012-01-01

    High scattered red amorphous nano selenium was synthesized in the presence of food-grade sodium alginate,employing SeO2 and NH2OH·HCl as the reactants.Then Nano selenium/chitosan composite particles were synthesized by compounding Nano selenium with chitosan and corn starch.The selenium sustained-release behavior of complex had been studied in simulation digestive juice,some factors influencing the release rate of selenium were systematically investigated,such as the pOH of simulation digestive juice,the sustained-release temperature and time.Experiments showed that Nano selenium complex was fit for slow-release.The optimal sustained-release conditions as follows:the pOH of simulation digestive juice was 12.8,sustained-release temperature was 38℃,sustained-release time was 2.8h.Under the condition,the release rate of selenium was up to 68.43%.The analysis capability of model was significant as the relative error between experimental result and model predicted value was 0.48%.%以盐酸羟胺、亚硒酸为反应物,食品级海藻酸钠为软模板,制备了分散性良好的红色无定形纳米硒。辅以壳聚糖、玉米淀粉,合成出了纳米硒-壳聚糖复合颗粒,在模拟消化液中研究了复合物的硒缓释行为,考察了模拟消化液pOH、缓释温度、缓释时间对硒释放率的影响。结果表明,含硒复合物适合于缓释,最佳缓释条件为:模拟消化液pOH=12.80,缓释温度38℃,缓释2.8h,纳米硒-壳聚糖复合物的硒释放率达到68.43%,实测结果与模型预测值的相对误差仅为0.48%。

  20. In vitro sustained release study of gallic acid coated with magnetite-PEG and magnetite-PVA for drug delivery system.

    Science.gov (United States)

    Dorniani, Dena; Kura, Aminu Umar; Hussein-Al-Ali, Samer Hasan; Bin Hussein, Mohd Zobir; Fakurazi, Sharida; Shaari, Abdul Halim; Ahmad, Zalinah

    2014-01-01

    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.

  1. 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.

  2. 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 < 0.0001), gained more FFM (p = <0.0001), and had a 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.

  3. 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.

  4. Development of Recombinant Human Growth Hormone (rhGH) sustained-release microspheres by a low temperature aqueous phase/aqueous phase emulsion method.

    Science.gov (United States)

    Kang, Jian; Wu, Fei; Cai, Yunpeng; Xu, Mingxin; He, Mu; Yuan, Weien

    2014-10-01

    A novel method has been developed to protect Recombinant Human Growth Hormone (rhGH) in poly (lactic-co-glycolic acid) (PLGA) microspheres using an aqueous phase/aqueous phase emulsion and S/O/W multi-emulsion method. This method develops a novel rhGH sustained-release system, which is based on the combination of rhGH-loaded dextran microparticles and PLGA microspheres. The process to fabricate rhGH-loaded dextran microparticles involves an aqueous phase/aqueous phase emulsion system formed at the reduced temperature. RhGH was first dissolved in water together with dextran and polyethylene glycol, followed by stirring at the speed of 2000 rpm for 20-30s at 0°C, and then a freezing process could enable the dextran phase to separate from the continuous PEG phase and rhGH could preferentially be loaded with dextran. The sample after freezing and phase separation was then lyophilized to powder and washed with dichloromethane to remove the PEG. Once loaded in the dextran microparticles (1-4 μm in diameter), rhGH gained resistance to interface tensions and was encapsulated into PLGA microspheres without aggregation thereafter. RhGH released from PLGA microspheres was in a sustained manner with minimal burst and maximally reduced incomplete release in vitro. Single subcutaneous injection of rhGH-loaded PLGA microspheres to rats resulted in a stable plasma concentration for 30 days avoiding the drug concentration fluctuations after multiple injections of protein solutions. In a hypophysectomized rat model, the IGF-1 and bodyweight results showed that there were higher than the levels obtained for the sustained release formulation by W/O/W for 40 days. These results suggest that the microsphere delivery system had the potential to be an injectable depot for sustained-release of the biocompatible protein of rhGH.

  5. A demonstration of the applicability of implementing the enhanced Remedial Action Priority System (RAPS) for environmental releases

    Energy Technology Data Exchange (ETDEWEB)

    Whelan, G.; Droppo, J.G. Jr.; Strenge, D.L.; Walter, M.B.; Buck, J.W.

    1989-12-01

    The Remedial Action Priority System (RAPS) and the Multimedia Environmental Pollutant Assessment System (MEPAS) were developed to prioritize problems associated with potential releases of hazardous chemical and radioactive materials in a scientific and objective manner based on limited site information. This report documents the model testing efforts of the RAPS/MEPAS methodology for the atmospheric, surface water, groundwater, and exposure components. Comparisons are given of model outputs with measured data at three sites: the US Department of Energy's Mound facility in Ohio and Hanford facility in Washington, and a chromium-cadmium plating site in New York. The results show that the simulated magnitudes, spacial and temporal trends, and distributions of contaminants corresponded well with the measured data. 25 refs., 86 figs., 26 tabs.

  6. Preparation and in vitro release of ginkgo biloba extract sustained-release tablets%银杏提取物缓释片的制备及其体外释放度的研究

    Institute of Scientific and Technical Information of China (English)

    崔启华; 朱云峰; 崔京浩

    2009-01-01

    目的:制备银杏提取物缓释片并考察其体外释放度.方法:以溶胀性材料羧甲基纤维素钠和羟丙甲基纤维素为骨架材料,直接粉末压片制备银杏提取物缓释片.根据单因素试验中各因素对银杏提取物体外释放度影响结果,进行正交设计,优化处方和工艺,以f_2相似因子法评价释放的差异.结果:羟丙甲基纤维素与羧甲基纤维素钠的用量比、羟丙甲基纤维素的黏度、不同的稀释剂均对药物释放有一定的影响,而缓释片的硬度、片重等对药物的释放没有显著的影响.结论:以羟丙甲基纤维素和羧甲基纤维素钠为骨架材料,制得持续释药12 h的银杏提取物缓释片.%Objective:To prepare ginkgo biloba extract (GBE) sustained-release tablets and observe its in vitro release profile.Method:GBE sustained-release tablets were prepared by direct compression method using sodium carboxymethylcellulose (CMC-Na) and hydroxypropyl methylcellulose HPMC) as matrix excipients.Based on the result of single-factor selecting experiment,the formulations and preparation process were optimized through orthogonal design,and release difference of tablets was evaluated with similarity factor (f_2).Result:The ratio of HPMC and CMC-Na,the viscosity of HPMC and the different types of the diluents had pronounced effect on the release of GBE sustained release tablets,ahhough the hardness and weight difference of tablets did not show notable influences.Conclusion:GBE sustained-release tablets that prepared by using the mixture of HPMC and CMC-Na display constant release profile in 12 h.

  7. 布洛芬缓释微丸的制备及释放度研究%PREPARATION AND STUDY ON RELEASE RATE OF SUSTAINED-RELEASE PELLETS OF IBUPROFEN

    Institute of Scientific and Technical Information of China (English)

    白翠莲; 孙虹; 许丽萍

    2015-01-01

    Objective:To prepare ibuprofen sustained-release pellets. Methods:Blank cores were prepared by means of powder layering with the PDL-Ⅱequipment,ibuprofen pellets were coated in the same equipment. Various factors influence on release rate and the release mechanism of the drug from the pellets was studied. Results:The optimal formula of the ibuprofen sustained release pellets were the following:pill core 100g,ibuprofen 300g,stearic acid 3g,PVP K 306g,and the dissolution test in vitro showed that they can meet with ibuprofen sustained release capsules launched. Release mechanism of the drug from pellets was in accordance with Higuchi equation:Q=-14. 814+38. 480t1/2(r=0. 996). Conclusions:The method and the formulation are successful in providing slow and steady release of ibuprofen from sustained-release pellets.%目的::制备布洛芬缓释微丸。方法:采用DPL-Ⅱ多功能制粒包衣机制备微晶纤维素空白丸芯和布洛芬含药微丸。用释放度测定法考察影响药物释放的各种因素,并对布洛芬缓释微丸体外释药机理进行研究。结果:布洛芬缓释微丸最佳处方为:丸芯100g、布洛芬300g、硬脂酸3g、PVP K 306 g,其释放度与市售产品(芬必得)拟合良好,体外释药过程基本符合Higuchi 方程:Q=-14.814+38.480t1/2(r=0.996)。结论:成功的制备了布洛芬缓释微丸。

  8. Analysis of the usage of sustained and controlled-release opioids in elderly patients with cancer%缓控释强阿片类药物在老年癌痛患者中的应用分析

    Institute of Scientific and Technical Informat