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Sample records for delayed release formulation

  1. Formulation, Development and Evaluation of delayed release capsules of Duloxetine Hydrochloride made of different Enteric Polymers

    Directory of Open Access Journals (Sweden)

    Pallavi Yerramsetty

    2012-03-01

    Full Text Available Delayed release systems have acquired a centre stage in the arena of pharmaceutical research and development. The present study involves formulation and evaluation of Duloxetine Hydrochloride delayed release capsules. Duloxetine Hydrochloride is an acid labile drug. It degrades in the acidic environment of the stomach thus leading to therapeutic inefficacy. Therefore it is necessary to bypass the acidic pH of the stomach which can be achieved by formulating delayed release dosage form by using different enteric polymers. Protection of drug from acidic environment is done by coating the drug with enteric polymers by using suspension layering technique in Fluidized bed processor (FBP with different enteric polymers like HPMCAS (Hydroxy Propyl Methyl Cellulose Acetate Succinate, Acryl EZE and HPMCP (Hydroxy propyl methyl cellulose phthalate.The formulation (E12 of delayed release capsules of Duloxetine Hydrochloride containing HPMCP (HP-55: HP- 50 as enteric polymer can be taken as optimized

  2. Superior Serum Concentrations with Posaconazole Delayed-Release Tablets Compared to Suspension Formulation in Hematological Malignancies

    OpenAIRE

    2015-01-01

    Posaconazole (PCZ), approved for prophylaxis against invasive fungal disease in high-risk patients, is commercially available orally as a suspension formulation (PCZ-susp) and as a delayed-release tablet (PCZ-tab). We evaluated the serum steady-state concentrations (Css) of PCZ stratified by the administered formulation for antifungal prophylaxis in patients with myeloid malignancies (n = 150). The primary outcome was the attainment rate of the target Css of ≥700 ng/ml. Secondary outcomes inc...

  3. Clinical utility of risedronate in postmenopausal osteoporosis: patient considerations with delayed-release formulation

    Directory of Open Access Journals (Sweden)

    Boyanov M

    2012-04-01

    Full Text Available Plamen Kinov1, Mihail Boyanov21Department of Orthopedics and Traumatology, University Hospital Queen Giovanna – ISUL, 2Department of Internal Medicine, Clinic of Endocrinology, University Hospital Alexandrovska, Medical University of Sofia, Sofia, BulgariaAbstract: Bisphosphonates are the most widely prescribed treatment for postmenopausal osteoporosis, secondary osteoporosis, and male osteoporosis. Notwithstanding their high effectiveness and favorable safety profile, the adherence to bisphosphonate treatment remains low. Different treatment strategies aim to improve the clinical effectiveness of bisphosphonate therapy. This review paper assesses the clinical utility of oral intermittent risedronate in the treatment of postmenopausal osteoporosis. The new delayed-release risedronate formulation is a safer and easy to use alternative to other risedronate therapy. Oral risedronate, a potent nitrogen-containing bisphosphonate, has been extensively studied using daily regimens. A new intermittent (weekly dosing regimen confirmed its clinical effectiveness in relation to vertebral and nonvertebral fracture prevention. The absence of significant differences in the incidence of adverse effects confirmed the favorable tolerability of the weekly dosage. In efforts to improve patient adherence to treatment, an innovative, delayed-release formulation of risedronate, which ensures adequate bioavailability of the active compound when taken with food, was introduced. The once-weekly delayed-release formulation of risedronate proved to be noninferior to the daily dosage of risedronate in terms of bone mineral density and markers of bone turnover. In addition, the incidence of new morphometric vertebral fractures was comparable in both treatment regimens. The new delayed-release formulation of risedronate showed a favorable safety profile. Delayed-release risedronate is a promising, new, effective, and convenient alternative to current bisphosphonate

  4. Review article: similarities and differences among delayed-release proton-pump inhibitor formulations.

    Science.gov (United States)

    Horn, J R; Howden, C W

    2005-12-01

    Proton-pump inhibitors are acid-labile, and require an enteric coating to protect them from degradation in the stomach when given orally. However, this leads to delayed absorption and onset of action of the proton-pump inhibitor. This article aims to review the similarities and differences between the various formulations of delayed release proton-pump inhibitors. Delayed-release omeprazole and delayed-release lansoprazole have been suspended in sodium bicarbonate for tube administration; however, for omeprazole, absorption is further impaired and antisecretory effects are disappointing. Although such formulations may be more convenient for clinical use in certain patient groups, absorption of the proton-pump inhibitor is still influenced by residual enteric coating. There are few differences among the currently available delayed-release proton-pump inhibitors with respect to their pharmacodynamic effects during chronic administration. There are minor formulation-based pharmacokinetic differences among these agents, primarily reflected in their bioavailability following the first few doses. Differences in bioavailability may explain slight differences in the rate of onset of maximal antisecretory effect. However, minor pharmacodynamic and pharmacokinetic differences are not associated with meaningful differences in clinical outcomes.

  5. Ronidazole pharmacokinetics in cats following delivery of a delayed-release guar gum formulation.

    Science.gov (United States)

    Papich, M G; Levine, D N; Gookin, J L; Davidson, G S; Stagner, W C; Hayes, R B

    2013-08-01

    Ronidazole (RDZ) is the only known effective treatment for feline diarrhea caused by Tritrichomonas foetus. This study aimed to develop guar gum-coated colon-targeted tablets of RDZ and to determine the pharmacokinetics of this delayed-release formulation in cats. Guar gum-coated tablets were administered orally once to five healthy cats (mean dose 32.3 mg/kg). The tablets were then administered once daily for 5 days to four cats (mean dose 34.5 mg/kg), and absorption studies repeated on day 5. Plasma was collected and analyzed for RDZ concentration, and pharmacokinetic noncompartmental and deconvolution analysis were performed on the data. There was negligible RDZ release until after 6 h, and a delayed peak plasma concentration (mean Cmax 28.9 μg/mL) at approximately 14.5 h, which coincides with colonic arrival in cats. Maximum input rate (mg/kg per hour) occurred between 6 and 16 h. This delayed release of ronidazole from guar gum-coated tablets indicates that release of RDZ may be delayed to deliver the medication to a targeted area of the intestine. Repeated dosing with guar gum tablets to steady-state did not inhibit drug bioavailability or alter the pharmacokinetics. Such targeted RDZ drug delivery may provide improved efficacy and reduce adverse effects in cats.

  6. Superior Serum Concentrations with Posaconazole Delayed-Release Tablets Compared to Suspension Formulation in Hematological Malignancies.

    Science.gov (United States)

    Cumpston, Aaron; Caddell, Ryan; Shillingburg, Alexandra; Lu, Xiaoxiao; Wen, Sijin; Hamadani, Mehdi; Craig, Michael; Kanate, Abraham S

    2015-08-01

    Posaconazole (PCZ), approved for prophylaxis against invasive fungal disease in high-risk patients, is commercially available orally as a suspension formulation (PCZ-susp) and as a delayed-release tablet (PCZ-tab). We evaluated the serum steady-state concentrations (Css) of PCZ stratified by the administered formulation for antifungal prophylaxis in patients with myeloid malignancies (n = 150). The primary outcome was the attainment rate of the target Css of ≥700 ng/ml. Secondary outcomes included toxicity assessment (hepatotoxicity and corrected QT [QTc] interval prolongation) and breakthrough fungal infections. Patients who received the PCZ-susp (n = 118) or PCZ-tab (n = 32) and had PCZ Css assessment after at least 7 days of therapy were eligible. The median Css in the PCZ-susp group was 390 ng/ml (range, 51 to 1,870 ng/ml; mean, 436 ng/ml) compared to 1,740 ng/ml (range, 662 to 3,350 ng/ml; mean, 1,781 ng/ml) in the PCZ-tab group (P < 0.0001). The percentages of patients achieving the target goal of ≥700 ng/ml were 17% versus 97%, respectively (P < 0.0001). Hepatotoxicity (grade 2 or higher) occurred in 1 patient in each group. QTc interval measurements were available for 32 patients in the PCZ-susp group and for 12 patients in the PCZ-tab group, and prolonged intervals of grade 2 or higher were noted in 9% (n = 3) and 17% (n = 2), respectively (P = 0.6). Breakthrough fungal infections in the PCZ-susp and PCZ-tab groups were 7% (n = 8) and 3% (n = 1), respectively (P = 0.68). We conclude that the use of PCZ-tab was associated with higher Css and with the probability of achieving therapeutic goals without worsening of adverse effects.

  7. 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.

  8. Controlled Release Formulations of Auxinic Herbicides

    Science.gov (United States)

    Kowalski, Witold J.; Siłowiecki, Andrzej.; Romanowska, Iwona; Glazek, Mariola; Bajor, Justyna; Cieciwa, Katarzyna; Rychter, Piotr

    2013-04-01

    Controlled release formulations are applied extensively for the release of active ingredients such as plant protection agents and fertilizers in response to growing concern for ecological problems associated with increased use of plant protection chemicals required for intensive agricultural practices [1]. We synthesized oligomeric mixtures of (R,S)-3-hydroxy butyric acid chemically bonded with 2,4-D, Dicamba and MCPA herbicides (HBA) respectively, and determined their molecular structure and molecular weight dispersion by the size exclusion chromatography, proton magnetic resonance spectrometry and electro-spray ionization mass spectrometry. Further we carried out bioassays of herbicidal effectiveness of the HBA herbicides vs. series of dicotyledonous weeds and crop injury tests [2, 3, 4]. Field bioassays were accomplished according to the EPPO standards [5]. Groups of representative weeds (the development stages in the BCCH scale: 10 - 30) were selected as targets. Statistical variabilities were assessed by the Fisher LSD test for plants treated with the studied herbicides in form of HBA oligomers, the reference herbicides in form of dimethyl ammonium salts (DMA), and untreated plants. No statistically significant differences in the crop injuries caused by the HBA vs. the DMA reference formulation were observed. The effectiveness of the HBA herbicides was lower through the initial period (ca. 2 weeks) relative to the DMA salts, but a significant increase in the effectiveness of the HBA systems followed during the remaining fraction of each assay. After 6 weeks all observed efficiencies approached 100%. The death of weeds treated with the HBA herbicides was delayed when compared with the DMA reference herbicides. The delayed uptake observed for the HBA oligomers relative to the DMA salts was due to controlled release phenomena. In case of the DMA salts the total amount of active ingredients was available at the target site. By contrast, the amount of an active

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

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    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.

  10. "Sustained release formulation of Metoclopramide Hydrochloride "

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    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.

  11. Development of particulate pulse-release formulations and their mathematical description

    NARCIS (Netherlands)

    Kok, PJAH; Vonk, P; Hoekzema, MA; Kossen, NWF

    2001-01-01

    In this contribution both the development of a multi-particulate delayed release system and a mathematical model to describe its release properties are presented. The formulation consists of a water-soluble core coated with a water-insoluble ethylcellulose coating. After immersing the formulation in

  12. Delayed-release lansoprazole plus naproxen.

    Science.gov (United States)

    Curran, Monique P; Wellington, Keri

    2004-01-01

    A combination package containing delayed-release capsules of the proton pump inhibitor lansoprazole (15 mg once daily) and tablets of the NSAID naproxen (375 or 500 mg twice daily) has been approved for reducing the risk of NSAID-associated gastric ulcers in NSAID-requiring patients with a documented history of gastric ulcer. In a large, 12-week trial in NSAID (including naproxen)-requiring patients with a documented history of gastric ulcer, significantly more recipients of delayed-release lansoprazole 15 mg once daily than placebo recipients were free from gastric ulcer (p ulcer were 80% with lansoprazole 15 mg and 51% with placebo. In a subgroup analysis of recipients of naproxen (89% received 750-1000 mg/day), the percentage of patients free from gastric ulcer after 12 weeks of treatment was significantly higher with delayed-release lansoprazole 15 mg than with placebo (89% vs 33%; p ulcer, the incidence of treatment-related adverse events in recipients of delayed-release lansoprazole 15 mg once daily was low (7%), and similar to that in recipients of placebo (10%).

  13. Preparation and characterization of slow release formulations of ...

    African Journals Online (AJOL)

    *

    characterize the resulting slow release formulations (SRFs) using scanning electron microscopy. (SEM), and Fourier ... used for controlled release of N-P-K compound fertilizer9 and of ..... fertilizer with controlled release and water retention,.

  14. Formulation and Dissolution Study of Valsartan Immediate Release Tablets

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    B. Brahmaiah*, K. Sasikanth, Sreekanth Nama , P.Suresh, Patan Adam Khan

    2013-06-01

    Full Text Available In the present study, design of oral immediate release tablets of Valsartan by direct compression techniquewas carried out. The main aim and objective of the work is to formulate immediate release tablets usingdifferent direct compression vehicles (DCV’S in different ratios. The main motive is to compare thedissolution profile of these formulations and conclude the best formulation which release drug at a fasterrate. To determine the best fit dissolution profile for the dosage forms. Valsartan tablets were formulated byusing microcrystalline cellulose (diluents, potato starch, acacia (binder and magnesium stearate(lubricant. The granules were compressed into tablets and were subjected to dissolution studies. Thedissolution profile of the formulation F2 was found to have better dissolution rate compared to others. TheIn-vitro dissolution studies of all the formulations were conducted and the results were obtained, it wasconcluded that formulation F2 was the best with fast release of drug compared to others.

  15. Formulation and Evaluation of Nateglinide Sustained Release Tablets

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    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.

  16. 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.

  17. Modifying sorbents in controlled release formulations to prevent herbicides pollution

    Energy Technology Data Exchange (ETDEWEB)

    Cespedes, F.F.; Sanchez, M.V.; Garcia, S.P.; Perez, M.F. [University of Almeria, Almeria (Spain). Dept. of Inorganic Chemistry

    2007-10-15

    The herbicides chloridazon and metribuzin, identified as groundwater pollutants, were incorporated in alginate-based granules to obtain controlled release properties. In this research the effect of incorporation of sorbents such as bentonite, anthracite and activated carbon in alginate basic formulation were not only studied on encapsulation efficiency but also on the release rate of herbicides which was studied using water release kinetic tests. In addition, sorption studies of herbicides with bentonite, anthracite and activated carbon were made. The kinetic experiments of chloridazon and metribuzin release in water have shown that the release rate is higher in metribuzin systems than in those prepared with chloridazon, which has lower water solubility. Besides, it can be deduced that the use of sorbents reduces the release rate of the chloridazon and metribuzin in comparison to the technical product and to the alginate formulation without sorbents. The highest decrease in release rate corresponds to the formulations prepared with activated carbon as a sorbent. The water uptake, permeability, and time taken for 50% of the active ingredient to be released into water, were calculated to compare the formulations. On the basis of a parameter of an empirical equation used to fit the herbicide release data, the release of chloridazon and metribuzin from the various formulations into water is controlled by a diffusion mechanism.

  18. Formulation and Evaluation of Darifenacin Hydrobromide Extended Release Matrix Tablets

    Directory of Open Access Journals (Sweden)

    Syed Meraj Sultana

    2016-08-01

    Full Text Available Darifenacin hydrobromide is a highly selective muscarinic (M3 receptor blocker that has been widely used for the treatment of overactive bladder syndrome. The bioavailability of darifenacin hydrobromide is 15–19% due to extensive first pass metabolism. Hence oral administration of darifenacin hydrobromide as extended tablets is a possible solution to overcome this problem. So the aim of the study was to formulate and evaluate Darifenacin hydrobromide extended release matrix tablets using extended release polymers like HPMC K4M, HPMC K15M and HPMC K100M, Metalose 60 SH-50 and Xanthum gum in different concentrations. Formulated tablets were characterized for different parameters like hardness, thickness, weight variation, friability, % Cumulative drug release etc. Nine formulations (F1 – F9 were formulated using direct compression technique. From the results obtained, it was concluded that the optimized formulation containing HPMC K15 M and K100M (1:2 showed better release up to 24hrs.The dissolution profiles and kinetic studies indicate that the release of Darifenacin Hydrobromide can be effectively controlled by the use of hydrophilic matrix systems. Different kinetic models were applied to the optimized formulation and observed that formulation (F9 followed first order kinetic model and Non-Fickian diffusion (or Anomalous transport as mechanism of drug release.

  19. Formulation of Extended-Release Metformin Hydrochloride Matrix ...

    African Journals Online (AJOL)

    Erah

    carrier, polymer and preparation method on metformin release from the formulations in vitro as well as ... Results: The physicochemical characteristics of all the granules and tablets were generally satisfactory. Optimization ..... Some physical.

  20. FORMULATION AND EVALUATION OF NIFEDIPINE SUSTAINED RELEASE PELLETS

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    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.

  1. Modifying sorbents in controlled release formulations to prevent herbicides pollution.

    Science.gov (United States)

    Flores Céspedes, F; Villafranca Sánchez, M; Pérez García, S; Fernández Pérez, M

    2007-10-01

    The herbicides chloridazon and metribuzin, identified as groundwater pollutants, were incorporated in alginate-based granules to obtain controlled release properties. In this research the effect of incorporation of sorbents such as bentonite, anthracite and activated carbon in alginate basic formulation were not only studied on encapsulation efficiency but also on the release rate of herbicides which was studied using water release kinetic tests. In addition, sorption studies of herbicides with bentonite, anthracite and activated carbon were made. The kinetic experiments of chloridazon and metribuzin release in water have shown that the release rate is higher in metribuzin systems than in those prepared with chloridazon, which has lower water solubility. Besides, it can be deduced that the use of sorbents reduces the release rate of the chloridazon and metribuzin in comparison to the technical product and to the alginate formulation without sorbents. The highest decrease in release rate corresponds to the formulations prepared with activated carbon as a sorbent. The water uptake, permeability, and time taken for 50% of the active ingredient to be released into water, T(50), were calculated to compare the formulations. On the basis of a parameter of an empirical equation used to fit the herbicide release data, the release of chloridazon and metribuzin from the various formulations into water is controlled by a diffusion mechanism. Sorption capacity of the sorbents for chloridazon and metribuzin, ranging from 0.53mgkg(-1) for the metribuzin sorption on bentonite to 2.03x10(5)mgkg(-1) for the sorption of chloridazon on the activated carbon, was the most important factor modulating the herbicide release.

  2. Cetirizine release from cyclodextrin formulated compressed chewing gum

    DEFF Research Database (Denmark)

    Stojanov, Mladen; Larsen, Kim Lambertsen

    2012-01-01

    Beside the efficient effect on masking cetirizine bitter taste, the cyclodextrins (CDs) as well could have influence on the release from the formulation. In vitro release profiles of cetirizine from compressed chewing gums containing α-, β- and γ-CD were investigated using a three cell chewing...

  3. FORMULATION AND DISSOLUTION STUDY OF DILTIAZEM HYDROCHLORIDE IMMEDIATE RELEASE TABLETS

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    BRAHMAIAH BONTHAGARALA

    2014-08-01

    Full Text Available Objective: The main aim and objective of the work is to formulate immediate release tablets using different direct compression vehicles (DCV’S in different ratios. Methods: In the present study, design of oral immediate release tablets of Diltiazem hydrochloride by direct compression technique was carried out. Results: The main motive is to compare the dissolution profile of these formulations and conclude the best formulation which release drug at a faster rate . To determine the best fit dissolution profile for the dosage forms. Diltiazem hydrochloride tablets were formulated by using microcrystalline cellulose (diluent, potato starch, acacia (binder and magnesium stearate (lubricant. The granules were compressed into tablets and were subjected to dissolution studies. The dissolution profile of the formulation F2 was found to have better dissolution rate compared to others. Conclusion: The Invitro dissolution studies of all the formulations were conducted and the results were obtained, it was concluded that formulation F2 was the best with fast release of drug compared to others.

  4. FORMULATION AND EVALUATION OF CANDESARTAN CILEXETIL IMMEDIATE RELEASE TABLETS

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    Jampani Neeharika

    2012-07-01

    Full Text Available Candesartan Cilexetil is an esterified prodrug of Candesartan, a non-peptide angiotensin II type-1(AT1 receptor antagonist used in the treatment of hypertension and congestive heart failure. Candesartan meets the requirement of high potency but it is poorly absorbed when administered orally. Therefore, the prodrug Candesartan Cilexetil is developed. It is soluble in methylene chloride, half life is 5.1 to 10.5hrs and bioavailability is 15%. It is marketed as conventional tablets. In this work, it is formulated as immediate release tablets by changing the concentration of ingredients. For many drug substances, conventional immediate-release formulations provide clinically effective therapy while maintaining the required balance of pharmacokinetic and pharmacodynamic profiles with in acceptable level of safety to the patient. The immediate release formulation of Candesartan Cilexetil is prepared by wet granulation method to provide rapid onset of action. In order to optimize the best formulation, ten different trials are developed. The main ingredients used in the formulation are lactose monohydrate, PEG, calcium CMC and MCC. Weight variation, thickness, friability, disintegration time, in-vitro release, pharmaceutical assay are studied as response variables. The formulation containing 38% of MCC is selected as an optimized product in which the different physical properties and in-vitro release profile showed best comparable results with innovator product.

  5. FORMULATION DEVELOPMENT OF ISOXSUPRINE HYDROCHLORIDE MODIFIED RELEASE MATRIX TABLETS

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    Ketan Patel

    2012-01-01

    Full Text Available The objective of the present investigation was to study the effect of critical formulation parameters affecting release of isoxsuprine hydrochloride from matrix tablets using combination of polyethylene oxide (PEO and dicalcium phosphate (DCP. The powder blend consisting of drug and excipients was analyzed for angle of repose, Carr’s index and Hausner’s ratio. The tablets were prepared by direct compression method. To assess the compressional behavior of the drug-excipient blend, the tablets were analyzed for friability and crushing strength. The in vitro drug release study was carried out in distilled water. The powder blend exhibited satisfactorily flow as measured by angle of repose, Carr’s index and Hausner’s ratio. The formulation ingredients showed satisfactory tableting properties (friability <1%, crushing strength ≥ 4 kgf. The drug release was modified on addition of PEO and DCP. Addition of 5 to 25% DCP in the formulation of matrix tablets caused apparent difference in the drug dissolution in distilled water. However, the difference was insignificant as analyzed by analysis of variance (ANOVA and similarity factor ( f2. The drug release from the tablets was best explained by Weibull model. Unified Weibull model was evolved to predict drug release from the formulated batches. The findings of this investigation can be extended to industry to cut down the cost of formulation and to by-pass the existing patents employing hydrophilic matrixing agents, at least for selective drugs.

  6. FORMULATION AND EVALUATION OF EXTENDED RELEASE TABLETS OF TRAMADOL HYDROCHLORIDE

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    Chilvalvar Sapnil

    2013-10-01

    Full Text Available The objective of this research work was to develop extended release tablets (Twice in a day of Tramadol Hydrochloride using different Hydrophilic polymers like HPMC K15M, HPMC K4M, Metalose 60SH50, Carbopol 971P, Sodium alginate, Xanthan gum by direct compression method. Various amounts of polymers was used in the twenty four proposed formulations (F1 to F24 for the study of release rate retardant effect at 10 %, 15 %, 20 %, 25 % of total weight of tablet matrix respectively. Then the tablets were evaluated in terms of their physical parameters (weight variation, hardness, friability and thickness, drug content and in-vitro release studies. All the formulations showed compliance with pharmacopoeial standards. The in-vitro dissolution study were conducted using USP dissolution apparatus type-II (paddle method in 900 ml 0.1 N HCl for first 2 h and remaining 10 h performed in 6.8 pH phosphate buffer at 100 rpm for a total period of 12 h. Based on the dissolution data comparison with innovator product, formulation F14 was found as the best formulation. The drug release of formulation F14 followed First Order kinetic model and the mechanism was found to be non-Fickian/anomalous according to Korsmeyer-Peppas equation.

  7. An oral controlled release matrix pellet formulation containing nanocrystalline ketoprofen.

    Science.gov (United States)

    Vergote, G J; Vervaet, C; Van Driessche, I; Hoste, S; De Smedt, S; Demeester, J; Jain, R A; Ruddy, S; Remon, J P

    2001-05-21

    A controlled release pellet formulation using a NanoCrystal colloidal dispersion of ketoprofen was developed. In order to be able to process the aqueous NanoCrystal colloidal dispersion into a hydrophobic solid dosage form a spray drying procedure was used. The in vitro dissolution profiles of wax based pellets loaded with nanocrystalline ketoprofen are compared with the profiles of wax based pellets loaded with microcrystalline ketoprofen and of a commercial sustained release ketoprofen formulation. Pellets were produced using a melt pelletisation technique. All pellet formulations were composed of a mixture of microcrystalline wax and starch derivatives. The starch derivatives used were waxy maltodextrin and drum dried corn starch. Varying the concentration of drum dried corn starch increased the release rate of ketoprofen but the ketoprofen recovery remained problematic. To increase the dissolution yield surfactants were utilised. The surfactants were either added during the production process of the NanoCrystal colloidal dispersion (sodium laurylsulphate) or during the pellet manufacturing process (Cremophor RH 40). Both methods resulted in a sustained but complete release of nanocrystalline ketoprofen from the matrix pellet formulations.

  8. 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.

  9. Review of the new delayed-release oral tablet and intravenous dosage forms of posaconazole.

    Science.gov (United States)

    Guarascio, Anthony J; Slain, Douglas

    2015-02-01

    The triazole antifungal posaconazole was first approved as an oral suspension formulation. Despite pharmacokinetic target attainment and clinical efficacy in premarketing trials, postmarketing analyses indicated unpredictable bioavailability resulting in subtherapeutic concentrations and reports of breakthrough fungal infections. The newly approved posaconazole delayed-release tablet and intravenous formulations display more consistent bioavailability in the presence of concomitant disease states, medications, and dietary considerations that classically alter drug concentrations of the oral suspension. Both the delayed-release tablet and intravenous formulation display a similar adverse-effect profile to the oral suspension. The posaconazole delayed-release oral tablet is not significantly affected by gastric acid suppression therapy, and the intravenous dosage form provides an option for patients who are intubated or unable to tolerate oral medications. Pharmacoeconomic considerations, particularly with intravenous posaconazole, will likely play a role in dosage form selection and frequency of use. Due to sustained, higher drug concentrations, the new posaconazole formulations hold promise for greater efficacy in antifungal prophylaxis and bring opportunity for further study in the treatment of invasive mycoses.

  10. Slow- Release Fertilizer Formulation Using Acrylic and Chitosan Coating

    Directory of Open Access Journals (Sweden)

    Lili Handayani

    2015-01-01

    Full Text Available The low-efficiency problem in fertilizer application can be overcome by controlling fertilizer solubility, i.e. by rendering the fertilizer to be released gradually; such material is also known as slow-release fertilizer (SRF. This research was aimed to formulate SRF by coating technique using acrylic and chitosan as the coating material, and to evaluate fertilizer resistance to too fast disintegration, and rate of nutrient release method. The results demonstrated that fertilizer formulation containing N, P, K, Fe, Cu, and Zn with granulation technique yielded 74% of granules with 2-5 mm in diameter. The SRFs (formulated fertilizer with acrylic or chitosan coating were more resistant to water pounding than non-SRF. Furthermore, shaking test with distilled water or 2% citric acid, or by percolation test with distilled water showed that the SRFs had lower nutrient solubility than the non-SRFs. The results of shaking test also specifically indicated that coating with acrylic made the fertilizer more resistant to the citric acid,suggesting that this coating material would be more suitable in acidic soils. The SRFs formulated with the addition of chitosan during blending of micronutrients prior to mixing with macronutrients, granulation, and final coating exhibited lower nutrient solubility than the SRFs without the pre-coating chitosan addition.

  11. Design of a controlled release liquid formulation of lamotrigine

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    V Kumar

    2011-05-01

    Full Text Available "n  "n  Background and the purpose of the study: Lamotrigine is a broad spectrum anticonvulsant drug widely used as mono- or adjunct- therapy in adults and children. The aim of this study was to develop controlled release liquid formulation of lamotrigine to improve bioavailability and compliance of pediatric and geriatric epileptic patients. "n  Methods: Multiple (w/o/w emulsion was prepared using one step emulsification technique. It was evaluated for entrapment efficiency (EE, morphology, zeta potential (ZP, polydispersity index (PI, rheology, thermal property, in vitro drug release behavior and stability. In vivo studies in albino mice were carried out using maximal electroshock seizure (MES test and strychnine induced seizure (SIS pattern test and results were compared with marketed formulation. "n  Results: The EE of the formulations varied from 84.37% to 98.11%. The ZP and PI values of the prepared batches were in the range of +23.46 to +28.07 and 0.256 and 0.365, respectively. Microscopic observation clearly indicated the stability of the emulsions during the storage period. All batches exhibited controlled in vitro drug release up to 12 hrs. Batch C11 exhibited significantly longer duration of protection of seizure in mice against MES and exhibited comparable efficacy in SIS as compared to the marketed formulation. "n  Major Conclusion: Multiple emulsion of lamotrigine compared to the marketed tablet showed plasma drug concentration within therapeutic range for longer time and comparable efficacy.

  12. Polymer micelles for delayed release of therapeutics from drug-releasing surfaces with nanotubular structures.

    Science.gov (United States)

    Sinn Aw, Moom; Addai-Mensah, Jonas; Losic, Dusan

    2012-08-01

    A new approach to engineer a local drug delivery system with delayed release using nanostructured surface with nanotube arrays is presented. TNT arrays electrochemically generated on a titanium surface are used as a model substrate. Polymer micelles as drug carriers encapsulated with drug are loaded at the bottom of the TNT structure and their delayed release is obtained by loading blank micelles (without drug) on the top. The delayed and time-controlled drug release is successfully demonstrated by controlling the ratio of blank and drug loaded-micelles. The concept is verified using four different polymer micelles (regular and inverted) loaded with water-insoluble (indomethacin) and water-soluble drugs (gentamicin).

  13. Comparative steady-state pharmacokinetic study of an extended-release formulation of itopride and its immediate-release reference formulation in healthy volunteers

    Directory of Open Access Journals (Sweden)

    Yoon S

    2014-01-01

    Full Text Available Seonghae Yoon,1,* Howard Lee,2,* Tae-Eun Kim,1 SeungHwan Lee,1 Dong-Hyun Chee,3 Joo-Youn Cho,1 Kyung-Sang Yu,1 In-Jin Jang1 1Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, 2Clinical Trials Center, Seoul National University Hospital, 3AbbVie Ltd., Seoul, Republic of Korea *These authors contributed equally to this work Background: This study was conducted to compare the oral bioavailability of an itopride extended-release (ER formulation with that of the reference immediate-release (IR formulation in the fasting state. The effect of food on the bioavailability of itopride ER was also assessed. Methods: A single-center, open-label, randomized, multiple-dose, three-treatment, three-sequence, crossover study was performed in 24 healthy male subjects, aged 22–48 years, who randomly received one of the following treatments for 4 days in each period: itopride 150 mg ER once daily under fasting or fed conditions, or itopride 50 mg IR three times daily in the fasting state. Steady-state pharmacokinetic parameters of itopride, including peak plasma concentration (Cmax and area under the plasma concentration versus time curve over 24 hours after dosing (AUC0–24h, were determined by noncompartmental analysis. The geometric mean ratio of the pharmacokinetic parameters was derived using an analysis of variance model. Results: A total of 24 healthy Korean subjects participated, 23 of whom completed the study. The geometric mean ratio and its 90% confidence interval of once-daily ER itopride versus IR itopride three times a day for AUC0–24h were contained within the conventional bioequivalence range of 0.80–1.25 (0.94 [0.88–1.01], although Cmax was reached more slowly and was lower for itopride ER than for the IR formulation. Food delayed the time taken to reach Cmax for itopride ER, but AUC0–24h was not affected. There were no serious adverse events and both formulations were

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

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    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.

  15. Delay Analysis and Formulation Inference of Signalized Intersection for Traffic Congestion Conditions

    Institute of Scientific and Technical Information of China (English)

    刘广萍; 丁建梅

    2004-01-01

    Vehicle delay is an important measure to evaluate the signal timings of signalized intersections.When optimization the signal control parameters, delays of vehicles from all approach directions of an intersection should be considered. Based on the analysis of the vehicle delay on an approach of intersection, directed against the typical condition of a congested intersection-over-saturated condition, the paper has analyzed and inferred the intersection delay dynamic formulation, and has established the relation between intersection delay,the signal timings, vehicle arrival rate and the queue lengths, and that provides useful information for understanding vehicle delay of signalized intersection and for establishing performance index function of signal timing optimization.

  16. Prevention of invasive fungal infections in immunocompromised patients: the role of delayed-release posaconazole

    Directory of Open Access Journals (Sweden)

    Soysal A

    2015-09-01

    Full Text Available Ahmet SoysalDivision of Pediatric Infectious Diseases, Department of Pediatrics, Faculty of Medicine, Marmara University, Istanbul, TurkeyAbstract: Posaconazole is a triazole antifungal agent that has broad-spectrum activity against many yeasts and filamentous fungi, including Candida species, Cryptococcus neoformans, Aspergillus species, and Zygomycetes. This drug has been approved for the prevention of invasive fungal infections in patients with neutropenia and for the treatment of invasive fungal infections in hematopoietic stem cell transplant recipients with graft-versus-host disease. Studies on the clinical efficacy, safety, tolerability, and cost-effectiveness of posaconazole therapy were performed using the oral suspension form of the drug. Pharmacokinetic studies have found that the oral suspension form of posaconazole has problemeatic bioavailability: its absorption is affected by concomitant medication and food. This article discusses the pharmacokinetic properties of the newly developed posaconazole delayed-release tablet formulation and reviews the efficacy, safety, and cost-effectiveness of both the oral suspension and the new tablet formulation. In conclusion, the posaconazole tablet formulation has better systemic bioavailability, thereby enabling once-daily administration and better absorption in the presence of concomitant medication and food. However, well-designed clinical studies are needed to evaluate the use of the tablet formulation in real-life settings.Keywords: posaconazole delayed-release tablet, prophylaxis, invasive fungal infections

  17. Encapsulated Urea-Kaolinite Nanocomposite for Controlled Release Fertilizer Formulations

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    Siafu Ibahati Sempeho

    2015-01-01

    Full Text Available Urea controlled release fertilizer (CRF was prepared via kaolinite intercalation followed by gum arabic encapsulation in an attempt to reduce its severe losses associated with dissolution, hydrolysis, and diffusion. Following the beneficiation, the nonkaolinite fraction decreased from 39.58% to 0.36% whereas the kaolinite fraction increased from 60.42% to 99.64%. The X-ray diffractions showed that kaolinite was a major phase with FCC Bravais crystal lattice with particle sizes ranging between 14.6 nm and 92.5 nm. The particle size varied with intercalation ratios with methanol intercalated kaolinite > DMSO-kaolinite > urea-kaolinite (KPDMU. Following intercalation, SEM analysis revealed a change of order from thick compact overlapping euhedral pseudohexagonal platelets to irregular booklets which later transformed to vermiform morphology and dispersed euhedral pseudohexagonal platelets. Besides, dispersed euhedral pseudohexagonal platelets were seen to coexist with blocky-vermicular booklets. In addition, a unique brain-form agglomeration which transformed into roundish particles mart was observed after encapsulation. The nanocomposites decomposed between 48 and 600°C. Release profiles showed that 100% of urea was released in 97 hours from KPDMU while 87% was released in 150 hours from the encapsulated nanocomposite. The findings established that it is possible to use Pugu kaolinite and gum arabic biopolymer to prepare urea CRF formulations.

  18. A new time-independent formulation of fractional release

    Science.gov (United States)

    Ostermöller, Jennifer; Bönisch, Harald; Jöckel, Patrick; Engel, Andreas

    2017-03-01

    The fractional release factor (FRF) gives information on the amount of a halocarbon that is released at some point into the stratosphere from its source form to the inorganic form, which can harm the ozone layer through catalytic reactions. The quantity is of major importance because it directly affects the calculation of the ozone depletion potential (ODP). In this context time-independent values are needed which, in particular, should be independent of the trends in the tropospheric mixing ratios (tropospheric trends) of the respective halogenated trace gases. For a given atmospheric situation, such FRF values would represent a molecular property.We analysed the temporal evolution of FRF from ECHAM/MESSy Atmospheric Chemistry (EMAC) model simulations for several halocarbons and nitrous oxide between 1965 and 2011 on different mean age levels and found that the widely used formulation of FRF yields highly time-dependent values. We show that this is caused by the way that the tropospheric trend is handled in the widely used calculation method of FRF.Taking into account chemical loss in the calculation of stratospheric mixing ratios reduces the time dependence in FRFs. Therefore we implemented a loss term in the formulation of the FRF and applied the parameterization of a mean arrival time to our data set.We find that the time dependence in the FRF can almost be compensated for by applying a new trend correction in the calculation of the FRF. We suggest that this new method should be used to calculate time-independent FRFs, which can then be used e.g. for the calculation of ODP.

  19. Novel anhydrous emulsions: formulation as controlled release vehicles.

    Science.gov (United States)

    Suitthimeathegorn, Orawan; Jaitely, Vikas; Florence, Alexander T

    2005-07-25

    Novel anhydrous emulsions, which may offer some advantages as depot or reservoir vehicles for lipophilic drugs in controlled delivery systems, were formulated using castor oil as the disperse phase and dimethicone or cyclopentasiloxane as the continuous phase. Among the emulsifiers studied only silicone surfactants (cyclomethicone/dimethicone copolyols) which were miscible in silicone oil stabilized the emulsions. Cyclomethicone/PEG/PPG-18/18 Dimethicone and Cyclopentasiloxane/PEG/PPG-18/18 Dimethicone were more effective in lowering the interfacial tension between castor oil and both dimethicone and cyclopentasiloxane. Emulsions formulated using either of these two surfactants were found to be stable against phase separation and exhibited least globule growth over 168 h. The average particle size was found to be 2-6 microm in these systems formed by probe sonication. Slow release patterns of 3H-dehydroepiandrosterone (DHEA) and 3H-dexamethasone solubilized in the disperse castor oil phase into an aqueous dialyzing medium were observed over 48 h.

  20. Novel mesalamine-loaded beads in tablets for delayed release of drug to the colon.

    Science.gov (United States)

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

    2012-01-01

    Novel 'beads-in-a-tablet' formulations (total weight ∼740-780 mg) have been prepared that meet USP 31 requirements for Delayed Release of mesalamine. Several methods are presented that overcome breakage of beads during tablet compaction were explored. Bead formulations comprise a combination of extrusion and spheronization to produce a relatively high drug load (80%), followed by coating (25%) with a colonic-targeted drug release polymer (polymethacrylates, Eudragit(®) S100), overcoated (3%) with hydroxypropyl methylcellulose (Opadry(®)) to improve bead binding and compactability, and using 20% coat of lactose/sodium starch glycolate (Explotab(®)) as binder/disintegrant/cushioning agent, thus allowing a sufficiently thick coating to be uniform and without being broken during tablet compaction. Then, the aforementioned beads were compressed into tablets at 1500 pounds of pressure containing 400 mg of mesalamine, and finally coating the compressed tablets with Surelease(®) (ethylcellulose):Opadry(®) = 1:0.5 ranging from 1.5-2.5% weight gain; the resulting tablets met USP 31 dissolution requirements for delayed release tablets.

  1. Pharmacokinetics and safety of posaconazole delayed-release tablets for invasive fungal infections

    Directory of Open Access Journals (Sweden)

    Wiederhold NP

    2015-12-01

    Full Text Available Nathan P Wiederhold Departments of Pathology and Medicine/Infectious Diseases, University of Texas Health Science Center at San Antonio, South Texas Reference Laboratories, San Antonio, TX, USA Abstract: Posaconazole is a broad-spectrum triazole antifungal agent with potent activity against various pathogenic fungi, including yeast and moulds. Clinical studies have demonstrated that this agent is efficacious as prophylaxis against invasive fungal infections in patients at high risk, and may also be useful as salvage therapy against invasive aspergillosis and mucormycosis. However, the bioavailability of posaconazole following administration by oral suspension, which was the only formulation clinically available for many years, is highly variable and negatively influenced by several factors. Because of this, many patients had subtherapeutic or undetectable posaconazole levels when the oral suspension was used. To overcome this limitation, a delayed-release tablet was developed and is now available for clinical use. Hot-melt extrusion technology is used to combine a pH-sensitive polymer with posaconazole to produce a formulation that releases the drug in the elevated pH of the intestine where absorption occurs rather than in the low-pH environment of the stomach. This results in enhanced bioavailability and increased posaconazole exposure. Studies in healthy volunteers have demonstrated significantly higher and more consistent exposures with the tablet formulation compared to the oral suspension. In addition, pharmacokinetic parameters following administration of the tablets were not significantly affected by medications that raise gastric pH or increase gastric motility, and the tablets could also be administered without regard to food. Similar results have also been found in patients at high risk for invasive fungal infections who have received posaconazole tablets. The tablet formulation also appears to be well tolerated to date, although data

  2. Multiple dose pharmacokinetics of a new once daily extended release tolterodine formulation versus immediate release tolterodine.

    Science.gov (United States)

    Olsson, B; Szamosi, J

    2001-01-01

    To determine the multiple dose pharmacokinetics of a new extended release (ER) capsule formulation of tolterodine, compared with the existing immediate release (IR) tablet, in healthy volunteers. Nonblind, randomised, 2-way crossover trial. 19 healthy volunteers (7 females, 12 males), mean age 33 years (range 18 to 55 years). Prior to the study, all volunteers were classified as either extensive or poor metabolisers by cytochrome P450 2D6 genotyping. Volunteers received tolterodine ER 4mg once daily or tolterodine IR 2mg twice daily for 6 days (all doses given as the L-tartrate salt). A washout period of 7 days separated the 2 treatments. Serum concentrations of tolterodine, its active 5-hydroxymethyl metabolite (5-HM) and the active moiety (extensive metabolisers: sum of unbound tolterodine + 5-HM; poor metabolisers: unbound tolterodine) were measured for up to 48 hours post-dose on day 6 (steady state). Tolerability was also determined. 17 volunteers (13 extensive metabolisers, 4 poor metabolisers) completed the study and were evaluable for both treatment periods. The 90% confidence interval for the geometric mean ratio of area under the serum concentration-time curve to 24 hours (AUC24) of the active moiety, for all volunteers combined, indicated equivalence for the 2 formulations. Pooled analysis also demonstrated that the peak serum concentration (Cmax) of the active moiety following administration of tolterodine ER was around 75% of that observed for the IR tablet, whereas the trough concentration was around 1.5-fold higher. Overall, the pharmacokinetics of tolterodine (irrespective of genotype) and 5-HM (extensive metabolisers only) were consistent with sustained drug release over 24 hours. Tolterodine ER was well tolerated. The new once daily ER formulation of tolterodine 4mg shows pharmacokinetic equivalence (AUC24) to the existing IR tablet given at a dose of 2mg twice daily. Findings of lower Cmax for tolterodine ER may explain the significantly lower

  3. Development and validation of dissolution testings in acidic media for rabeprazole sodium delayed-release capsules.

    Science.gov (United States)

    Tan, Yinhe; Si, Xiaoqing; Zhong, Lulu; Feng, Xin; Yang, Xinmin; Huang, Min; Wu, Chuanbin

    2016-10-01

    Rabeprazole sodium (RAB) dissolved in acidic media is accompanied by its degradation in the course of dissolution testing. To develop and establish the accumulative release profiles of ACIPHEX(®) Sprinkle (RAB) delayed-release capsules (ACIPHEX(®) Sprinkle) in acidic media using USP apparatus 2 (paddle apparatus) as a dissolution tester, the issues of determination of accumulative release amount of RAB in these acidic media and interference of hydroxypropylmethyl cellulose phthalate were solved by adding appropriate hydrochloric acid (HCl) into dissolution samples coupled with centrifugation so as to remove the interference and form a solution of degradation products of RAB, which is of a considerably stable ultraviolet (UV) absorbance at the wavelength of 298 nm within 2.0 h. Therefore, the accumulative release amount of RAB in dissolution samples at each sample time points could be determined by UV-spectrophotometry, and the accumulative release profiles of ACIPHEX(®) Sprinkle in the media of pH 1.0, pH 6.0, and pH 6.8 could be established. The method was validated per as the ICH Q2 (R1) guidelines and demonstrated to be adequate for quality control of ACIPHEX(®) Sprinkle and the accumulative release profiles can be used as a tool to guide the formulation development and quality control of a generic drug for ACIPHEX(®) Sprinkle.

  4. Prevention of invasive fungal infections in immunocompromised patients: the role of delayed-release posaconazole.

    Science.gov (United States)

    Soysal, Ahmet

    2015-01-01

    Posaconazole is a triazole antifungal agent that has broad-spectrum activity against many yeasts and filamentous fungi, including Candida species, Cryptococcus neoformans, Aspergillus species, and Zygomycetes. This drug has been approved for the prevention of invasive fungal infections in patients with neutropenia and for the treatment of invasive fungal infections in hematopoietic stem cell transplant recipients with graft-versus-host disease. Studies on the clinical efficacy, safety, tolerability, and cost-effectiveness of posaconazole therapy were performed using the oral suspension form of the drug. Pharmacokinetic studies have found that the oral suspension form of posaconazole has problemeatic bioavailability: its absorption is affected by concomitant medication and food. This article discusses the pharmacokinetic properties of the newly developed posaconazole delayed-release tablet formulation and reviews the efficacy, safety, and cost-effectiveness of both the oral suspension and the new tablet formulation. In conclusion, the posaconazole tablet formulation has better systemic bioavailability, thereby enabling once-daily administration and better absorption in the presence of concomitant medication and food. However, well-designed clinical studies are needed to evaluate the use of the tablet formulation in real-life settings.

  5. 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.

  6. Pharmacokinetics and safety of posaconazole delayed-release tablets for invasive fungal infections.

    Science.gov (United States)

    Wiederhold, Nathan P

    2016-01-01

    Posaconazole is a broad-spectrum triazole antifungal agent with potent activity against various pathogenic fungi, including yeast and moulds. Clinical studies have demonstrated that this agent is efficacious as prophylaxis against invasive fungal infections in patients at high risk, and may also be useful as salvage therapy against invasive aspergillosis and mucormycosis. However, the bioavailability of posaconazole following administration by oral suspension, which was the only formulation clinically available for many years, is highly variable and negatively influenced by several factors. Because of this, many patients had subtherapeutic or undetectable posaconazole levels when the oral suspension was used. To overcome this limitation, a delayed-release tablet was developed and is now available for clinical use. Hot-melt extrusion technology is used to combine a pH-sensitive polymer with posaconazole to produce a formulation that releases the drug in the elevated pH of the intestine where absorption occurs rather than in the low-pH environment of the stomach. This results in enhanced bioavailability and increased posaconazole exposure. Studies in healthy volunteers have demonstrated significantly higher and more consistent exposures with the tablet formulation compared to the oral suspension. In addition, pharmacokinetic parameters following administration of the tablets were not significantly affected by medications that raise gastric pH or increase gastric motility, and the tablets could also be administered without regard to food. Similar results have also been found in patients at high risk for invasive fungal infections who have received posaconazole tablets. The tablet formulation also appears to be well tolerated to date, although data regarding clinical efficacy are needed.

  7. Constructing Slow-Release Formulations of Ammonium Nitrate Fertilizer Based on Degradable Poly(3-hydroxybutyrate).

    Science.gov (United States)

    Boyandin, Anatoly Nikolayevich; Kazantseva, Eugenia Andreevna; Varygina, Daria Eugenievna; Volova, Tatiana Grigorievna

    2017-08-16

    The present study describes construction and investigation of experimental formulations of ammonium nitrate embedded in a matrix of degradable natural polymer poly-3-hydroxybutyrate [P(3HB)] and P(3HB) blended with wood flour shaped as tablets, some of them coated with P(3HB). Kinetics of ammonium release into soil as dependent on the composition of the polymer matrix was investigated in laboratory experiments. The rates of fertilizer release from formulations coated with a biopolymer layer were considerably (two months or longer) slower than the rates of fertilizer release from uncoated formulations, while release from polymer and composite (polymer/wood flour) formulations occurred with comparable rates. The use of the experimental formulations in laboratory ecosystems with wheat (Triticum aestivum L.) was more effective than application of free ammonium nitrate. The advantage of the slow-release fertilizer formulations is that they are buried in soil together with the seeds, and the fertilizer remains effective over the first three months of plant growth. The use of such slow-release formulations will reduce the amounts of chemicals released into the environment, which will curb their accumulation in food chains of ecosystems and mitigate their adverse effects on the biosphere.

  8. A new oral formulation for the release of sodium butyrate in the ileo-cecal region and colon

    Institute of Scientific and Technical Information of China (English)

    Aldo Roda; Patrizia Simoni; Maria Magliulo; Paolo Nanni; Mario Baraldini; Giulia Roda; Enrico Roda

    2007-01-01

    AIM:To develop a new formulation with hydroxy propyl methyl cellulose and Shellac coating for extended and selective delivery of butyrate in the ileo-caecal region and colon.METHODS:One-gram sodium butyrate coated tablets containing 13C-butyrate were orally administered to 12 healthy subjects and 12 Crohn's disease patients and the rate of 13C-butyrate absorption was evaluated by 13CO2 breath test analysis for eight hours.Tauroursodeoxycholic acid(500 mg)was co-administered as a biomarker of oro-ileal transit time to determine also the site of release and absorption of butyrate by the time of its serum maximum concentration.RESULTS:The coated formulation delayed the 13C-butyrate release by 2-3 h with respect to the uncoated tablets.Sodium butyrate was delivered in the intestine of all subjects and a more variable transit time was found in Crohn's disease patients than in healthy subjects.The variability of the peak 13CO2 in the kinetic release of butyrate was explained by the inter-subject variability in transit time.However,the coating chosen ensured an efficient release of the active compound even in patients with a short transit time.CONCLUSION:Simultaneous evaluation of breath 13CO2 and tauroursodeoxycholic acid concentrationtime curves has shown that the new oral formulation consistently releases sodium butyrate in the ileo-cecal region and colon both in healthy subjects and Crohn's disease patients with variable intestinal transit time.This formulation may be of therapeutic value in inflammatory bowel disease patients due to the appropriate release of the active compound.

  9. Formulation development and release studies of indomethacin suppositories

    Directory of Open Access Journals (Sweden)

    Sah M

    2008-01-01

    Full Text Available Indomethacin suppositories were prepared by using water-soluble and oil soluble suppository bases, and evaluated for in vitro release by USP I and modified continuous flow through bead bed apparatus. Effect of the Tween 80 (1% and 5% was further studied on in vitro release of the medicament. Release rate was good in water-soluble suppositories bases in comparison to oil soluble suppositories bases. Release was found to be greater in modified continuous flow through bead bed apparatus. When surfactant was used in low concentration then release rate was much greater, as compared to high concentration. When stability studies were performed on the prepared indomethacin suppositories it was found that suppositories made by water-soluble base had no significant changes while suppositories prepared by oil soluble bases, had some signs of instability.

  10. Retrospective Comparison of Posaconazole Levels in Patients Taking the Delayed-Release Tablet versus the Oral Suspension.

    Science.gov (United States)

    Durani, Urshila; Tosh, Pritish K; Barreto, Jason N; Estes, Lynn L; Jannetto, Paul J; Tande, Aaron J

    2015-08-01

    While posaconazole prophylaxis decreases the risk of invasive fungal infection compared to fluconazole, low bioavailability of the oral-suspension formulation limits its efficacy. A new delayed-release tablet formulation demonstrated an improved pharmacokinetic profile in healthy volunteers. However, serum levels for the two formulations have not been compared in clinical practice. This study compared achievement of therapeutic posaconazole levels in patients taking the delayed-release tablet to those taking the oral suspension. This retrospective cohort study included 93 patients initiated on posaconazole between 2012 and 2014 and had at least one serum posaconazole level measured. The primary measure was the proportion of patients achieving an initial therapeutic level (>700 ng/ml). An initial therapeutic posaconazole level was seen in 29 of 32 (91%) patients receiving tablets and 37 of 61 (61%) patients receiving suspension (P = 0.003). Among patients with a steady-state level measured 5 to 14 days after initiation, a therapeutic level was observed in 18 of 20 (90%) patients receiving tablets and 25 of 43 (58%) patients receiving suspension (P = 0.01). In these patients, the median posaconazole level of the tablet cohort (1655 ng/ml) was twice that of the suspension cohort (798 ng/ml) (P = 0.004). In this cohort study, the improved bioavailability of delayed-release posaconazole tablets translates into a significantly higher proportion of patients achieving therapeutic serum levels than in the cohort receiving the oral suspension. The results of this study strongly support the use of delayed-release tablets over suspension in patients at risk for invasive fungal infection.

  11. Hydroxypropyl methylcellulose based cephalexin extended release tablets: influence of tablet formulation, hardness and storage on in vitro release kinetics.

    Science.gov (United States)

    Saravanan, Muniyandy; Sri Nataraj, Kalakonda; Ganesh, Kettavarampalayam Swaminath

    2003-08-01

    The object of this study was to develop hydroxypropyl methylcellulose (HPMC) based cephalexin extended release tablet, which can release the drug for six hours in predetermined rate. Twenty-one batches of cephalexin tablets were prepared by changing various physical and chemical parameters, in order to get required theoretical release profile. The influences of HPMC, microcrystalline cellulose powder (MCCP), granulation technique, wetting agent and tablet hardness on cephalexin release from HPMC based extended release tablets were studied. The formulated tablets were also characterized by physical and chemical parameters. The dissolution results showed that a higher amount of HPMC in tablet composition resulted in reduced drug release. Addition of MCCP resulted in faster drug release. Tablets prepared by dry granulation was released the drug slowly than the same prepared with a wet granulation technique. Addition of wetting agent in the tablets prepared with dry granulation technique showed slower release. An increase in tablet hardness resulted in faster drug release. Tablets prepared with a wet granulation technique and having a composition of 9.3% w/w HPMC with a hardness of 10-12 kg/cm(2) gave predicted release for 6 h. The in vitro release data was well fit in to Higuchi and Korsmeyer-Peppas model. Physical and chemical parameters of all formulated tablets were within acceptable limits. One batch among formulated twenty-one batches was successful and showed required theoretical release. The effect of storage on in vitro release and physicochemical parameters of successful batch was studied and was found to be in acceptable limits.

  12. Development and Evaluation of Extended Release Formulation of Tramadol Hydrochloride Based on Osmotic Technology

    Directory of Open Access Journals (Sweden)

    Patel JB

    2013-05-01

    Full Text Available Extended release formulation of Tramadol Hydrochloride based on osmotic technology was developedand evaluated. Target release profile was selected and different variables were optimized to achieve it.Formulation variables such as osmotic agent, plasticizer and coating thickness of semi-permeablemembrane were found to markedly affect drug release. Tramadol hydrochloride release was directlyproportional to the level of osmogent and plasticizer but inversely proportional to the level of coatingthickness of semi-permeable membrane. Drug release from developed formulation was independent ofpH and agitation intensity but dependent on osmotic pressure of release media. The optimizedformulation was compared with marketed product CONTRAMAL SR and accelerated stability studywas also carried out for 6 months.

  13. Encapsulated Urea-Kaolinite Nanocomposite for Controlled Release Fertilizer Formulations

    National Research Council Canada - National Science Library

    Sempeho, Siafu Ibahati; Kim, Hee Taik; Mubofu, Egid; Pogrebnoi, Alexander; Shao, Godlisten; Hilonga, Askwar

    2015-01-01

    Urea controlled release fertilizer (CRF) was prepared via kaolinite intercalation followed by gum arabic encapsulation in an attempt to reduce its severe losses associated with dissolution, hydrolysis, and diffusion...

  14. Formulation optimization of hydrodynamically balanced oral controlled release bioadhesive tablets of tramadol hydrochloride.

    Science.gov (United States)

    Singh, Bhupinder; Rani, Ashu; Babita; Ahuja, Naveen; Kapil, Rishi

    2010-01-01

    The directly compressible floating-bioadhesive tablets of tramadol were formulated using varying amounts Carbopol 971P (CP) and hydroxy-propylmethyl cellulose (HPMC), along with other requisite excipients. In vitro drug release profile, floatational characteristics and ex vivo bioadhesive strength using texture analyzer were determined, and systematically optimized using a 3(2) central composite design (CCD). The studies indicated successful formulation of gastroretentive compressed matrices with excellent controlled release, mucoadhesion and hydrodynamic balance. Comparison of the dissolution profiles of the optimized formulation, with optimal composition of CP:HPMC :: 80.0:125.0, with that of the marketed controlled release formulation other indicated analogy of drug release performance with each other. Validation of optimization study using eight confirmatory experimental runs indicated very high degree of prognostic ability of CCD with mean  SEM of â0.06%  0.37. Further, the study successfully unravels the effect of the polymers on the selected response variables.

  15. Effect of formulation composition on the properties of controlled release tablets prepared by roller compaction.

    Science.gov (United States)

    Hariharan, Madhusudan; Wowchuk, Christina; Nkansah, Paul; Gupta, Vishal K

    2004-07-01

    This study discusses the effect of formulation composition on the physical characteristics and drug release behavior of controlled-release formulations made by roller compaction. The authors used mixture experimental design to study the effect of formulation components using diclofenac sodium as the model drug substance and varying relative amounts of microcrystalline cellulose (Avicel), hydroxypropyl methylcellulose (HPMC), and glyceryl behenate (Compritol). Dissolution studies revealed very little variability in drug release. The t70 values for the 13 formulations were found to vary between 260 and 550 min. A reduced cubic model was found to best fit the t70 data and gave an adjusted r-square of 0.9406. Each of the linear terms, the interaction terms between Compritol and Avicel and between all three of the tested factors were found to be significant. The longest release times were observed for formulations having higher concentrations of HPMC or Compritol. Tablets with higher concentrations of Avicel showed reduced ability to retard the release of the drug from the tablet matrix. Crushing strength showed systematic dependence on the formulation factors and could be modeled using a reduced quadratic model. The crushing strength values were highest at high concentrations of Avicel, while tablets with a high level of Compritol showed the lowest values. A predicted optimum formulation was derived by a numerical, multiresponse optimization technique. The validity of the model for predicting physical attributes of the product was also verified by experiment. The observed responses from the calculated optimum formulation were in very close agreement with values predicted by the model. The utility of a mixture experimental design for selecting formulation components of a roller compacted product was demonstrated. These simple statistical tools can allow a formulator to rationally select levels of various components in a formulation, improve the quality of products, and

  16. Influence of alcohol on the release of tramadol from 24-h controlled-release formulations during in vitro dissolution experiments.

    Science.gov (United States)

    Traynor, M J; Brown, M B; Pannala, A; Beck, P; Martin, G P

    2008-08-01

    Recent warnings by regulatory bodies and a product recall by the FDA have generated much interest in the area of dose dumping from controlled-release opioid analgesic formulations when coingested with alcohol. It was the aim of this study to address this issue and in doing so, gain understanding on how alcohol-induced effects may be avoided. In this study, tramadol release from Ultram ER tablets and T-long capsules was significantly increased in the presence of ethanol. Conversely, a decrease in the rate of tramadol release was seen from Tridural extended-release tablets in the presence of alcohol.

  17. 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.

  18. Formulation and Pharmacokinetic Evaluation of Controlled-Release ...

    African Journals Online (AJOL)

    ISSN: 1596-5996 (print); 1596-9827 (electronic) ... Purpose: To develop and optimize controlled-release (CR) oxybutynin chloride matrix tablets. Methods: ... of the tablet was developed. ... India). Hydroxypropyl methylcellulose (HPMC) 4KM CR and ethyl cellulose (EC) were ..... Lyrinel OROS, and OXY/CR5C4 in SGF media.

  19. MODIFIED RELEASE FORMULATIONS TO ACHIEVE THE QUALITY TARGET PRODUCT PROFILE (QTPP

    Directory of Open Access Journals (Sweden)

    Mithilesh Kumar Jha

    2012-08-01

    Full Text Available Modified Release (MR Formulations have a modification in the release mechanism. Modified release dosage forms are developed by altering drug absorption or the site of drug release in order to achieve predetermined clinical objectives. Modified drug release from dosage forms is complemented by the allied processes of drug design, of dosage administration, and of membrane transport and absorption of drug to the biological site of action. Modified-release drugs have complex formulations that can offer an advantage over standard medication for some patients. Modified-release preparations should only be used where there is a clear clinical advantage over conventional-release preparations. In general, Modified-release preparations should be reserved for specific patients where there is a problem with compliance, effectiveness or side-effects which these preparations could help overcome. Modified–release technologies have become indispensable to resolving critical technical, therapeutic, and marketing challenges, such as improving patience compliance, less dosage timings, better safety, better indications, delivering poorly soluble and poorly absorbable API’s, product differentiation, patent protection, product life-cycle extension, and better margins. Modified-release formulation design can be conducted for oral and non-oral administration routes. Possible therapeutic benefits of an MR product include improved efficacy and reduced adverse events, increased convenience and patient compliance, optimized performance, a greater selectivity of activity, or new indications.

  20. Formulation and characterization of modified release tablets containing isoniazid using swellable polymers.

    Science.gov (United States)

    Akhtar, M F; Rabbani, M; Sharif, A; Akhtar, B; Saleem, A; Murtaza, G

    2011-01-01

    The aim of this work was to develop swellable modified release (MR) isoniazid tablets using different combinations of polyvinyl acetate (PVAc) and sodium-carboxymethylcellulose (Na-CMC). Granules were prepared by moist granulation technique and then compressed into tablets. In vitro release studies for 12 hr were carried out in dissolution media of varying pH i.e. pH 1.2, 4.5, 7.0 and 7.5. Tablets of all formulations were found to be of good physical quality with respect to appearance (width and thickness), content uniformity, hardness, weight variation and friability. In vitro release data showed that increasing total polymer content resulted in more retarding effect. Formulation with 35% polymer content exhibited zero order release profile and it released 35% of the drug in first hr, later on, controlled drug release was observed upto the 12(th) hour. Formulations with PVAc to Na-CMC ratio 20:80 exhibited zero order release pattern at levels of studied concentrations, which suggested that this combination can be used to formulate zero order release tablets of water soluble drugs like isoniazid. Korsmeyer-Peppas modeling of drug release showed that non-Fickian transport is the primary mechanism of isoniazid release from PVAc and Na-CMC based tablets. The value of mean dissolution time decreased with the increase in the release rate of drug clearly showing the retarding behavior of the swellable polymers. The application of a mixture of PVAc to Na-CMC in a specific ratio may be feasible to formulate zero order release tablets of water soluble drugs like isoniazid.

  1. Formulation and evaluation of ranolazine extended release tablets: Influence of polymers

    Directory of Open Access Journals (Sweden)

    TEGK Murthy

    2011-01-01

    Full Text Available An extended release tablet provides prolonged periods of drug in plasma levels thereby reduce dosing frequency, improve patient compliance and reduce the dose-related side effects. Ranolazine is indicated for the chronic treatment of angina in patients who have not achieved an adequate response with other anti-anginal agents. The present investigation was undertaken to design extended release tablets of Ranolazine employing hypromellose phthalate grade HP-55, ethocel standard 7FP premium ethyl cellulose, Surelease E-7-19040, Klucel HF pharm and Natrosol Type 250 HHX as matrix forming agents using wet granulation method. Formulated tablets were evaluated for uniformity of weight, assay, water content, in vitro drug release studies and stability studies. The drug release followed first order kinetics with both erosion and diffusion as the release mechanism. It is concluded that the desired drug release pattern can be obtained by using natrosol type 250 HHX compared to other polymers. The similarity factor (f2 was calculated to select best formulation by comparing in vitro dissolution data of the commercial formulation Ranexa® . The formulated tablets fulfilled the compendia requirements. The formulated Ranolazine Extended release tablets were found to be stable.

  2. Encapsulated Urea-Kaolinite Nanocomposite for Controlled Release Fertilizer Formulations

    OpenAIRE

    Siafu Ibahati Sempeho; Hee Taik Kim; Egid Mubofu; Alexander Pogrebnoi; Godlisten Shao; Askwar Hilonga

    2015-01-01

    Urea controlled release fertilizer (CRF) was prepared via kaolinite intercalation followed by gum arabic encapsulation in an attempt to reduce its severe losses associated with dissolution, hydrolysis, and diffusion. Following the beneficiation, the nonkaolinite fraction decreased from 39.58% to 0.36% whereas the kaolinite fraction increased from 60.42% to 99.64%. The X-ray diffractions showed that kaolinite was a major phase with FCC Bravais crystal lattice with particle sizes ranging betwee...

  3. Encapsulated Urea-Kaolinite Nanocomposite for Controlled Release Fertilizer Formulations

    OpenAIRE

    Siafu Ibahati Sempeho; Hee Taik Kim; Egid Mubofu; Alexander Pogrebnoi; Godlisten Shao; Askwar Hilonga

    2015-01-01

    Urea controlled release fertilizer (CRF) was prepared via kaolinite intercalation followed by gum arabic encapsulation in an attempt to reduce its severe losses associated with dissolution, hydrolysis, and diffusion. Following the beneficiation, the nonkaolinite fraction decreased from 39.58% to 0.36% whereas the kaolinite fraction increased from 60.42% to 99.64%. The X-ray diffractions showed that kaolinite was a major phase with FCC Bravais crystal lattice with particle sizes ranging betwee...

  4. 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

  5. FORMULATION AND EVALUATION OF DICLOFENAC CONTROLLED RELEASE TABLETS EMPLOYING OLIBANUM RESIN

    Directory of Open Access Journals (Sweden)

    K.P.R. Chowdary and G. Rami Reddy *

    2012-04-01

    Full Text Available The objective of the study is to evaluate Olibanum resin, a natural resin polymer as matrix polymer for controlled release tablets and to design matrix tablets of diclofenac for controlled release. Matrix tablets of diclofenac were formulated employing Olibanum resin in different proportions of drug and polymer and the tablets were evaluated for drug release kinetics and mechanism .Two diluents namely lactose (water soluble and DCP (water insoluble were included in the formulations to assess their influence on drug release characteristics of olibanum resin matrix tablets. Matrix tablets were found t¬o be non- disint-egrating in water, acidic (pH 1.2 and alkaline (pH 7.4 fluids and were considered suitable for oral controlled release. Diclofenac release from the matrix tablets formulated was slow and spread over 24 h and depended on the concentration (% of olibanum resin in the matrix tablets and nature/type of diluent. As the concentration of olibanum resin in the matrix tablets was increased, drug release was decreased. Release was relatively faster with water soluble diluent lactose when compared to water insoluble diluent DCP at all concentrations of olibanum resin. Drug release from the tablets followed first order kinetics and followed non - Fickian (anomalous diffusion release mechanism. Good linear relationships were observed between percent polymer and release rate in each case. The results of the study thus indicated olibanum resin could be used as rate controlling matrix in design of controlled release tablets. Both water soluble and water insoluble diluents can be included in the olibanum resin matrix tablets without affecting its rate controlling efficiency. Matrix tablets formulated employing olibanum resin(DF2 are considered suitable for controlled release of diclofenac over 24 h (i.e. once-a-day administration.

  6. 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.

  7. Effect of methyl cellulose on gelation behavior and drug release from poloxamer based ophthalmic formulations.

    Science.gov (United States)

    Dewan, Mitali; Bhowmick, Biplab; Sarkar, Gunjan; Rana, Dipak; Bain, Mrinal Kanti; Bhowmik, Manas; Chattopadhyay, Dipankar

    2015-01-01

    The effect of weight average molecular weight (Mw) of methyl cellulose (MC) on the gelation behavior of Poloxamer 407 (PM) and in vitro release of Ketorolac Tromethamine (KT) from different ophthalmic formulations based on PM is examined. A drop of gelation temperature of PM is observed using MC of various M(w) by test tube tilting method, UV-vis spectroscopy, viscometry and rheometry. It is also observed that the viscosity and gel strength of all the formulations are increased with the increase in Mw of MC. PM with highest Mw of MC provides best drug release property among all the formulations. It is evident from this investigation that there is a distinct effect of M(w) of MC on the gelation behavior of PM as well as on the drug release profile of KT from PM-MC based ophthalmic formulations.

  8. Predicting release and transport of pesticides from a granular formulation during unsaturated diffusion in porous media

    DEFF Research Database (Denmark)

    Paradelo Pérez, Marcos; Soto-Gómez, Diego; Pérez-Rodrígez, Paula

    2014-01-01

    The release and transport of active ingredients (AIs) from controlled-release formulations (CRFs) have potential to reduce groundwater pesticide pollution. These formulations have a major effect on the release rate and subsequent transport to groundwater. Therefore the influence of CRFs should...... be included in modeling non-point source pollution by pesticides. We propose a simplified approach that uses a phase transition equation coupled to the diffusion equation that describes the release rate of AIs from commercial CRFs in porous media; the parameters are as follows: a release coefficient......, the solubility of the AI, and diffusion transport with decay. The model gives acceptable predictions of the pesticides release from commercial CRFs in diffusion cells filled with quartz sand. This approach can be used to study the dynamics of the CRF-porous media interaction. It also could be implemented in fate...

  9. Controlled poorly soluble drug release from solid self-microemulsifying formulations with high viscosity hydroxypropylmethylcellulose.

    Science.gov (United States)

    Yi, Tao; Wan, Jiangling; Xu, Huibi; Yang, Xiangliang

    2008-08-07

    The objective of this work was the development of a controlled release system based on self-microemulsifying mixture aimed for oral delivery of poorly water-soluble drugs. HPMC-based particle formulations were prepared by spray drying containing a model drug (nimodipine) of low water solubility and hydroxypropylmethylcellulose (HPMC) of high viscosity. One type of formulations contained nimodipine mixed with HPMC and the other type of formulations contained HPMC and nimodipine dissolved in a self-microemulsifying system (SMES) consisting of ethyl oleate, Cremophor RH 40 and Labrasol. Based on investigation by transmission electron microscopy (TEM), scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and X-ray powder diffraction, differences were found in the particle structure between both types of formulations. In vitro release was performed and characterized by the power law. Nimodipine release from both types of formulations showed a controlled release profile and the two power law parameters, n and K, correlated to the viscosity of HPMC. The parameters were also influenced by the presence of SMES. For the controlled release solid SMES, oil droplets containing dissolved nimodipine diffused out of HPMC matrices following exposure to aqueous media. Thus, it is possible to control the in vitro release of poorly soluble drugs from solid oral dosage forms containing SMES.

  10. Formulation and evaluation of controlled release floating microspheres of tolperisone hydrochloride

    Directory of Open Access Journals (Sweden)

    Pooja Jani

    2012-01-01

    Full Text Available Main aim of this study was to develop controlled release (CR floating multiparticulate drug delivery system of tolperisone hydrochloride. Microspheres were prepared by nonaqueous solvent evaporation technique consisting of porous calcium silicate (Florite or FLR as porous carrier, tolperisone hydrochloride (API, Ethyl cellulose (EC, and HPMC 15 cPs as rate controlling polymers. 2 3 full factorial design was applied for optimization of formulation. The effect of various formulation and process variables on the particle morphology, micromeritic properties, in vitro floating behavior, entrapment efficiency, and in vitro drug release were studied. The size of microspheres was varied from 300 to 500 μm. The microspheres were found to be highly porous and regular in shape. All the formulations showed excellent flow properties. The percentage entrapment efficiency of all batches was greater than 80%. The percentage buoyancy varied from 85% to 98% at the end of 12 h. The release rate was determined in simulated gastric fluids. The formulation demonstrated favorable in vitro floating and release characteristics. Different kinetic models were applied to study the release mechanism. All formulations followed Higuchi model, which indicates the diffusion control release of water soluble drug from polymer matrix. Multiple regression analysis was applied for study of the effect of independent variables on the dependent variables.

  11. Formulation and evaluation of dorzolamide hydrochloride-loaded nanoparticles as controlled release drug delivery system

    Directory of Open Access Journals (Sweden)

    Azza A Hasan

    2012-01-01

    Full Text Available This study aimed to prepare anti-glaucomatous dorzolamide hydrochloride-(Dorzo loaded nanoparticles as a controlled release system. Eudragit RS 100 (RS and/or RL 100 (RL were used in formulations by an opportunely adapted Quasi-emulsion solvent diffusion technique. The formulations were evaluated in terms of particle size, zeta potential, drug entrapment, and release profile. All formulations showed tiny particle size varying from 114 to 395 nm for RS and 65 to 277 nm for RL. Positive zeta potential was +19 to +32 mV for RS and +23 to +42 mV for RL formulations. It was demonstrated that increasing polymer concentration lead to increase the percentage of drug entrapped in all batches, to a certain extent (drug: polymer 1:4. Nanoparticles prepared using RL showed lower entrapment efficiency than RS. In contrast, increasing the stirring rate resulted in an increase in the percentage of Dorzo entrapped. A prolonged drug release was shown by all the formulations. Increasing the polymer concentration caused a decrease in the release rate. Moreover, it was evident that increasing RL content increased the amount of Dorzo released. Dorzo-loaded nanoparticles could represent promising drug ophthalmic carriers, due to small particle size, positive zeta potential, and sustained release profile; hence, expecting prolonged corneal contact time, more therapeutically efficient, decreased frequency of administration per day, and better patient compliance.

  12. 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.

  13. Formulation and evaluation of once daily minocycline hydrochloride extended release matrix tablets

    Directory of Open Access Journals (Sweden)

    Keny R

    2009-01-01

    Full Text Available The present study was aimed to develop once daily extended release matrix tablets of minocycline hydrochloride, using hydroxypropylmethylcellulose either alone or in combination with ethyl cellulose as the matrix material in different proportions. The formulated tablets were also compared with a marketed product. The results of the dissolution study indicate that formulations FC-IV, FC-V and FC-VI showed maximum drug release upto 24 h, whereas the marketed product was found to extend the release only up to 14 h. Incase of formulations containing combination of hydroxypropylmethylcellulose and ethyl cellulose (FC-I to FC-IX, the release of the drug was found to be dependent on the relative proportions of hydroxypropylmethylcellulose and ethyl cellulose used in the tablet matrix. Mathematical treatment of the in vitro drug release data suggests that, all the formulations best fitted into first order release kinetics. Drug release from the matrix occurred by combination of two mechanisms, diffusion of drug from tablet matrix and erosion of tablet surface, which was reflected from Higuchi′s model and Erosion plot.

  14. Development of a controlled release formulation by continuous twin screw granulation: Influence of process and formulation parameters.

    Science.gov (United States)

    Vanhoorne, V; Vanbillemont, B; Vercruysse, J; De Leersnyder, F; Gomes, P; Beer, T De; Remon, J P; Vervaet, C

    2016-05-30

    The aim of this study was to evaluate the potential of twin screw granulation for the continuous production of controlled release formulations with hydroxypropylmethylcellulose as hydrophilic matrix former. Metoprolol tartrate was included in the formulation as very water soluble model drug. A premix of metoprolol tartrate, hydroxypropylmethylcellulose and filler (ratio 20/20/60, w/w) was granulated with demineralized water via twin screw granulation. After oven drying and milling, tablets were produced on a rotary Modul™ P tablet press. A D-optimal design (29 experiments) was used to assess the influence of process (screw speed, throughput, barrel temperature and screw design) and formulation parameters (starch content of the filler) on the process (torque), granule (size distribution, shape, friability, density) and tablet (hardness, friability and dissolution) critical quality attributes. The torque was dominated by the number of kneading elements and throughput, whereas screw speed and filling degree only showed a minor influence on torque. Addition of screw mixing elements after a block of kneading elements improved the yield of the process before milling as it resulted in less oversized granules and also after milling as less fines were present. Temperature was also an important parameter to optimize as a higher temperature yielded less fines and positively influenced the aspect ratio. The shape of hydroxypropylmethylcellulose granules was comparable to that of immediate release formulations. Tensile strength and friability of tablets were not dependent on the process parameters. The use of starch as filler was not beneficial with regard to granule and tablet properties. Complete drug release was obtained after 16-20h and was independent of the design's parameters.

  15. Formulation Development and Stability Studies of Norfloxacin Extended-Release Matrix Tablets

    Directory of Open Access Journals (Sweden)

    Paulo Renato Oliveira

    2013-01-01

    Full Text Available The aim of this research was to develop a new hydrophilic matrix system containing norfloxacin (NFX. Extended-release tablets are usually intended for once-a-day administration with benefits to the patient and lower discontinuation of the therapy. Formulations were developed with hydroxypropylmethylcellulose or poly(ethylene oxide as hydrophilic polymers, with different molecular weights (MWs and concentrations (20 and 30%. The tablets were found to be stable (6 months at 40±2°C and 75±5% relative humidity, and the film-coating process is recommended to avoid NFX photodegradation. The dissolution profiles demonstrated an extended-release of NFX for all developed formulations. Dissolution curves analyzed using the Korsmeyer exponential equation showed that drug release was controlled by both drug diffusion and polymer relaxation or erosion mechanisms. A more erosion controlled system was obtained for the formulations containing lower MW and amount of polymer. With the increase in both MW and amount of polymer in the formulation, the gel layer became stronger, and the dissolution was more drug-diffusion dependent. Formulations containing intermediate MW polymers or high concentration (30% of low MW polymers demonstrated a combination of extended and complete in vitro drug release. This way, these formulations could provide an increased bioavailability in vivo.

  16. 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.

  17. Formulation Development and Stability Studies of Norfloxacin Extended-Release Matrix Tablets

    Science.gov (United States)

    Oliveira, Paulo Renato; Klein, Lilian; Sangoi, Maximiliano da Silva; Bernardi, Larissa Sakis; Silva, Marcos Antônio Segatto

    2013-01-01

    The aim of this research was to develop a new hydrophilic matrix system containing norfloxacin (NFX). Extended-release tablets are usually intended for once-a-day administration with benefits to the patient and lower discontinuation of the therapy. Formulations were developed with hydroxypropylmethylcellulose or poly(ethylene oxide) as hydrophilic polymers, with different molecular weights (MWs) and concentrations (20 and 30%). The tablets were found to be stable (6 months at 40 ± 2°C and 75 ± 5% relative humidity), and the film-coating process is recommended to avoid NFX photodegradation. The dissolution profiles demonstrated an extended-release of NFX for all developed formulations. Dissolution curves analyzed using the Korsmeyer exponential equation showed that drug release was controlled by both drug diffusion and polymer relaxation or erosion mechanisms. A more erosion controlled system was obtained for the formulations containing lower MW and amount of polymer. With the increase in both MW and amount of polymer in the formulation, the gel layer became stronger, and the dissolution was more drug-diffusion dependent. Formulations containing intermediate MW polymers or high concentration (30%) of low MW polymers demonstrated a combination of extended and complete in vitro drug release. This way, these formulations could provide an increased bioavailability in vivo. PMID:24083235

  18. Continuous twin screw granulation of controlled release formulations with various HPMC grades.

    Science.gov (United States)

    Vanhoorne, V; Janssens, L; Vercruysse, J; De Beer, T; Remon, J P; Vervaet, C

    2016-09-25

    HPMC is a popular matrix former to formulate tablets with extended drug release. Tablets with HPMC are preferentially produced by direct compression. However, granulation is often required prior to tableting to overcome poor flowability of the formulation. While continuous twin screw granulation has been extensively evaluated for granulation of immediate release formulations, twin screw granulation of controlled release formulations including the dissolution behavior of the formulations received little attention. Therefore, the influence of the HPMC grade (viscosity and substitution degree) and the particle size of theophylline on critical quality attributes of granules (continuously produced via twin screw granulation) and tablets was investigated in the current study. Formulations with 20 or 40% HPMC, 20% theophylline and lactose were granulated with water at fixed process parameters via twin screw granulation. The torque was influenced by the viscosity and substitution degree of HPMC, but was not a limiting factor for the granulation process. An optimal L/S ratio was selected for each formulation based on the granule size distribution. The granule size distributions were influenced by the substitution degree and concentration of HPMC and the particle size of theophylline. Raman and UV spectroscopic analysis on 8 sieve fractions of granules indicated an inhomogeneous distribution of theophylline over the size fractions. However, this phenomenon was not correlated with the hydration rate or viscosity of HPMC. Controlled release of theophylline could be obtained over 24h with release profiles close to zero-order. The release of theophylline could be tailored via selection of the substitution degree and viscosity of HPMC.

  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. 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.

  1. Pharmacokinetic considerations of formulation: extended-release metoprolol succinate in the treatment of heart failure.

    Science.gov (United States)

    Wikstrand, John; Andersson, Bert; Kendall, Martin J; Stanbrook, Hilary; Klibaner, Michael

    2003-02-01

    Extended-release (ER) metoprolol succinate is a controlled-release formulation designed to deliver metoprolol succinate at a near constant rate for approximately 20 h, independent of food intake and gastrointestinal pH. Once-daily dosing of ER metoprolol succinate 12.5-200 mg produces even plasma concentrations over a 24-h period, without the marked peaks and troughs characteristically observed with the immediate-release (IR) formulation. This leads to consistent beta1-blockade over 24 h, while maintaining cardioselectivity at doses up to 200 mg daily. Pharmacokinetic studies have also been performed in heart failure patients and have demonstrated that ER metoprolol succinate is associated with a more pronounced and even beta1-blockade over a 24-h period than the IR formulation. The efficacy and good tolerability of ER metoprolol succinate in heart failure patients has now been demonstrated in a large-scale clinical trial.

  2. Formulation and evaluation of novel controlled release of topical pluronic lecithin organogel of mefenamic acid.

    Science.gov (United States)

    Jhawat, Vikas; Gupta, Sumeet; Saini, Vipin

    2016-11-01

    In the present study, pluronic lecithin based organogels (PLO gels) were formulated as topical carrier for controlled delivery of mefenamic acid. Ten organogel formulations were prepared by a method employing lecithin as lipophilic phase and pluronic F-127 as hydrophilic phase in varying concentrations to study various parameters using in vitro diffusion study and in vivo studies. All formulations were found to be off-white, homogenous, and reluctant to be washed easily and have pH value within the range of 5.56-5.80 which is nonirritant. Polymer concentration increased in formulations of F1 to F5 (lecithin) and F6 to F10 (pluronic) resulted in decrease of the gelation temperature, increase of viscosity and reduction of spreadability of gels having polymer tendency to form rigid 3D network. Organogels with higher viscosity were found to be more stable and retard the drug release from the gel. The formulations of F2 and F3 were selected for kinetic studies and stability studies, as they found to have all physical parameters within acceptable limits, highest percent drug content and exhibited highest drug release in eight hours. The order of drug release from various formulations was found to be F2 > F3 > F10 > F4 > F1 > F9 > F8 > F5 > F7 > F6. The optimized formulation F2 was found to follow zero order rate kinetics showing controlled release of the drug from the formulations. In vivo anti-inflammatory activity of optimized mefenamic acid organogel (F2) against a standard marketed preparation (Volini gel) was found satisfactory and significant.

  3. CONTROLLED RELEASE FORMULATION DEVELOPMENT AND EVALUATION OF FELODIPINE MATRIX TABLETS BY USING HYDROPHOBIC POLYMERS

    Directory of Open Access Journals (Sweden)

    S. Kiran Kumar*, T. Ramarao, D.B.R.N. Bikshapathi and K.N. Jayaveera

    2013-01-01

    Full Text Available Felodipine is a long-acting 1, 4-dihydropyridine calcium channel blocker, used to control hypertension by selective action on peripheral resistance. The conventional felodipine tablet gives a rather high peak and comparatively low trough levels, due to rapid absorption and distribution. More sustained plasma concentrations might thus produce a more even effect on blood pressure. The main aim of the study was to improve dissolution rate of the dosage form in a controlled manner over extended period of 24 hrs. Matrix tablets were prepared by direct compression method,using hydrophobic polymers like Glyceryl monostearate and Carnauba wax. The prepared formulations were evaluated for hardness, thickness, weight variation, friability and in-vitro dissolution studies. Among all the formulations F8 was selected as optimized formulation based on the evaluation parameters and in-vitro release profile of 100% drug release for 24 hrs. The FTIR and DSC results of optimized formulation showed no drug-excipient interaction. For optimized formulation(F8, the drug release mechanism was explored and explained by zero-order (r2=0.984, first-order (r2=0.947, Higuchi (r2=0.967 and Korsmayer-peppas (r2=0.982 & n=0.855 equations, which explained the drug release follows zero-order and is fit for Higuchi equation & mechanism was anomalous diffusion i.e diffusion and erosion.

  4. Characterization of organogel as a novel oral controlled release formulation for lipophilic compounds.

    Science.gov (United States)

    Iwanaga, Kazunori; Sumizawa, Toru; Miyazaki, Makoto; Kakemi, Masawo

    2010-03-30

    A low molecular mass gelator can form soft solids in a variety of organic liquids and vegetable oils. These soft solids are generally called organogels. In this study, we prepared organogel using 12-hydroxystearic acid (12-HSA) as a gelator for soybean oil and investigated its characteristics as a controlled release formulation for lipophilic compounds. The release rate of ibuprofen, a model lipophilic compound, from organogel decreased with the increase of 12-HSA concentration in the formulation; however, the difference in the concentration of 12-HSA in the formulation did not affect the diffusivity of ibuprofen in the organogel. The erosion constant of organogel in the intestinal tract was examined by using simulated gastric fluid and intestinal fluid. Regardless of 12-HSA concentration in the formulation, organogel is very stable in the simulated gastric fluid. On the other hand, the erosion constant of organogel in the simulated intestinal fluid increased with the decreasing concentration of 12-HSA. Therefore, it is speculated that the difference in the release rate of ibuprofen among organogels with various concentrations of 12-HSA was mainly caused by the difference in the erosion rate. To characterize the organogel effect in vivo, ibuprofen was orally administered to rats in an aqueous suspension or organogel. Ibuprofen concentration in plasma rapidly increased after administration with an aqueous suspension, whereas organogel suppressed the rapid absorption. In conclusion, organogel is clearly useful as an oral controlled release formulation for lipophilic compounds.

  5. Formulation of unidirectional release buccal patches of carbamazepine and study of permeation through porcine buccal mucosa

    Institute of Scientific and Technical Information of China (English)

    Parthasarathy Govindasamy; Bhaskar Reddy Kesavan; Jayaveera Korlakunta Narasimha

    2013-01-01

    Objective:To achieve transbuccal release of carbamazepine by loading in unidirectional release mucoadhesive buccal patches. Methods:Buccal patches of carbamazepine with unidirectional drug release were prepared using hydroxypropyl methyl cellulose, polyvinyl alcohol, polyvinyl pyrrolidone and ethyl cellulose by solvent casting method. Water impermeable backing layer (Pidilite® Biaxially-oriented polypropylene film) of patches provided unidirectional drug release. They were evaluated for thickness, mass uniformity, surface pH and folding endurance. Six formulations FA2, FA8, FA10, FB1, FB14 and FB16 (folding endurance above 250) were evaluated further for swelling studies, ex vivo mucoadhesive strength, ex vivo mucoadhesion time, in vitro drug release, ex vivo permeation, accelerated stability studies and FTIR and XRD spectral studies. Results: The ex vivo mucoadhesion time of patches ranged between 109 min (FA10) to 126 min (FB14). The ex vivo mucoadhesive force was in the range of 0.278 to 0.479 kg/m/s. The in vitro drug release studies revealed that formulation FA8 released 84%and FB16 released 99.01%of drug in 140 min. Conclusions: The prepared unidirectional buccal patches of carbamazepine provided a maximum drug release within specified mucoadhesion period and it indicates a potential alternative drug delivery system for systemic delivery of carbamazepine.

  6. FORMULATION AND EVALUATION OF ORAL CONTROLLED RELEASE DOSAGE FORM OF ANTI-HYPERTENSIVE AGENT

    Directory of Open Access Journals (Sweden)

    Lakshmi Parvathi A

    2012-12-01

    Full Text Available The aim of present investigation is preparation, characterization and evaluation of oral controlled release matrix tablets of Propranolol HCl in order to improve efficacy and to reduce the side effects. Tablets were prepared by direct compression method using different polymers like Guar gum, HPMC K4M, PVP and MCC used as the directly compressible vehicle. The granules were evaluated for pre-formulation characteristics and the tablets were subjected to post compression parameters, drug content and in-vitro dissolution release studies. In-vitro dissolution studies were carried out for 12 hrs and the results showed that among the nine formulations F8 and F9 showed good dissolution profile to control the drug release respectively. The drug release follows first order kinetics and the mechanism was found to be diffusion controlled for all the formulations (except F-9. The mechanism of drug release from F-9 was diffusion coupled with erosion. The Stability studies were carried out according to ICH guideline which indicates that the selected formulations (F8 and F9 were stable. In conclusion the results suggest that the developed matrix tablets of Propranolol HCl could perform therapeutically better than conventional dosage form, leading to improved efficacy and better patient compliance.

  7. Release of rosmarinic acid from semisolid formulations and its penetration through human skin ex vivo

    Directory of Open Access Journals (Sweden)

    Stelmakienė Ada

    2015-06-01

    Full Text Available The aim of this study was to evaluate the release of rosmarinic acid (RA from the experimental topical formulations with the Melissa officinalis L. extract and to evaluate its penetration through undamaged human skin ex vivo. The results of the in vitro release study showed that higher amounts of RA were released from the emulsion vehicle when lemon balm extract was added in its dry form. An inverse correlation was detected between the released amount of RA and the consistency index of the formulation. Different penetration of RA into the skin may be influenced by the characteristics of the vehicle as well as by the form of the extract. The results of penetration assessment showed that the intensity of RA penetration was influenced by its lipophilic properties: RA was accumulating in the epidermis, while the dermis served as a barrier, impeding its deeper penetration.

  8. Formulation and evaluation of bilayer tablet for bimodal release of venlafaxine hydrochloride

    OpenAIRE

    2015-01-01

    The aim of the present research was to develop a bilayer tablet of venlafaxine hydrochloride for bimodal drug release. In the present investigation authors have tried to explore fenugreek mucilage (FNM) for bioadhesive sustained release layer. The attempt has been made to combine FNM with well studied bioadhesive polymers like hydroxy propyl methyl cellulose (HPMC), Carbopol, and Xanthan Gum. The formulations were evaluated for swelling Index, ex vivo bioadhesion, water uptake studies, in vit...

  9. 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

  10. Development and Optimization of a Novel Prolonged Release Formulation to Resist Alcohol-Induced Dose Dumping

    OpenAIRE

    Gujjar, Chaitanya Yogananda; Rallabandi, Balaramesha Chary; Gannu, Ramesh; Deulkar, Vallabh Subashrao

    2015-01-01

    Alcohol-induced dose dumping is a serious concern for the orally administered prolonged release dosage forms. The study was designed to optimize the independent variables, propylene glycol alginate (PGA), Eudragit RS PO (ERS) and coating in mucoadhesive quetiapine prolonged release tablets 200 mg required for preventing the alcohol-induced dose dumping. Optimal design based on response surface methodology was employed for the optimization of the composition. The formulations are evaluated for...

  11. Formulation And Evaluation Of Bilayer Tablet for Bimodal Release of Venlafaxine Hydrochloride

    Directory of Open Access Journals (Sweden)

    Munira eMomin

    2015-07-01

    Full Text Available The aim of the present research was to develop a bilayer tablet of venlafexine hydrochloride for bimodal drug release. In the present investigation authors have tried to explore Fenugreek Mucilage (FNM for bioadhesive sustained release layer. The attempt has been made to combine FNM with well studied bioahesive polymers like Hydroxy Propyl Methyl Cellulose, Carbopol and Xanthan Gum. The formulations were evaluated for swelling Index, ex-vivo bioadhesion, water uptake studies, in-vitro drug release and dissolution kinetics was studied. Substantial bioadhesion force (2.4±0.023 gms and tablet adhesion retention time (24±2 hrs was observed with FNM and HPMC combination at 80:20 ratio. The dissolution kinetics followed the Higuchi model (R2 =0.9913 via a non-Fickian diffusion controlled release mechanism after the initial burst. The 32 full factorial design was employed in the present study. The type of polymers used in combination with FNM (X1 and percent polymer replaced with FNM (X2 were taken as independent formulations variables. The selected responses, bioadhesion force (0.11-0.25±0.023gm, amount of drug released in 10 h, Y10 (78.20–95.78±1.24 % and bioadhesive strength, (19-24±2hrs presented good correlation with the selected independent variables. Statistical analysis (ANOVA of the optimized bilayer formulations showed no significant difference in the cumulative amount of drug release after 15 min, but significant difference (p < 0.05 in the amount of drug released after 1 hr till 12 h from optimized formulations was observed. The natural mucilage like FNM could be successfully incorporated into tablet with only 20% replacement with HPMC and it showed good bioadhesiveness and sustained drug release.

  12. The influence of metoprolol dosage release formulation on the pharmacokinetic drug interaction with paroxetine

    OpenAIRE

    Stout, Stephen M.; Nielsen, Jace; Welage, Lynda S; Shea, Michael; Brook, Robert; Kerber, Kevin; Bleske, Barry E

    2010-01-01

    Studies have demonstrated an influence of dosage release formulations on drug interactions and enantiomeric plasma concentrations. Metoprolol is a commonly used β-adrenergic antagonist metabolized by CYP2D6. The CYP2D6 inhibitor paroxetine has previously been shown to interact with metoprolol tartrate. This open-label, randomized, 4 phase crossover study assessed the potential differential effects of paroxetine on stereoselective pharmacokinetics of immediate release (IR) tartrate and extende...

  13. 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.

  14. 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.

  15. Development of a HPMC-based controlled release formulation with hot melt extrusion (HME).

    Science.gov (United States)

    Ma, Decheng; Djemai, Abdenour; Gendron, Colleen M; Xi, Hanmi; Smith, Michelle; Kogan, Jessica; Li, Li

    2013-07-01

    The objective of this study was to develop hydroxypropyl methylcellulose (HPMC) based controlled release (CR) formulations via hot melt extrusion (HME) with a highly soluble crystalline active pharmaceutical ingredient (API) embedded In the polymer phase. HPMC is considered a challenging CR polymer for extrusion due to its high glass transition temperature (Tg), low degradation temperature, and high viscosity. These problems were partially overcome by plasticizing the HPMC with up to 40% propylene glycol (PG). Theophylline was selected as the model API. By using differential scanning calorimetry (DSC), thermal gravimetric analysis (TGA), dynamic mechanical analysis (DMA), and X-ray powder diffraction (XRPD), the physical properties of the formulations were systematically characterized. Five grades of HPMC (Methocel(®)) - E6, K100LV, K4M, K15M, and K100M - were tested. The extrusion trials were conducted on a 16 mm twIn screw extruder with HPMC/PG placebo and formulations containing theophylline/HPMC/PG (30:42:28, w/w/w). The dissolution results showed sustained release profiles without burst release for the HPMC K4M, K15M, and K100M formulations. The extrudates have good dissolution stability after being stressed for 2 weeks under 40°C/75% RH open dish conditions and the crystalline API form did not change upon storage. Overall, the processing windows were established for the HPMC based HME-CR formulations.

  16. Effect of combination of acrylic polymers on the release of nevirapine formulated as extended release matrix pellets using extrusion and spheronization technique.

    Science.gov (United States)

    Sharma, Anshuli; Prasad, Anjaneya; Dua, Kamal; Singh, Gurvinder

    2014-01-01

    The aim of the present research work was to formulate and evaluate the extended release matrix pellets of nevirapine using extrusion and spheronization technique which will be an alternative technique for making extended release dosage forms and to compare the drug release profiles of the formulations with the reference product. In vitro dissolutions were carried out in 0.04M Phosphate buffer pH 6.8 with 2% w/v SLS (sodium lauryl sulphate) for 24 hours with USP type I apparatus at 75rpm. The drug release from the optimised formulation was comparable to that of the reference product and follows first order kinetics followed by non-fickian transport mechanism of drug release which confirms the drug release pattern involves complex mixture of diffusion and erosion. The similarity factor, f2 value of optimised formulation was found to be 70, which shows that the developed formulation was comparable to that of the reference product.

  17. Formulation and evaluation of controlled release matrix mucoadhesive tablets of domperidone using Salvia plebeian gum

    Directory of Open Access Journals (Sweden)

    Gurpreet Arora

    2011-01-01

    Full Text Available The aim of study was to prepare controlled release matrix mucoadhesive tablets of domperidone using Salvia plebeian gum as natural polymer. Tablets were formulated by direct compression technology employing the natural polymer in different concentrations (5, 10, 15 and 20% w/w. The prepared batches were evaluated for drug assay, diameter, thickness, hardness and tensile strength, swelling index, mucoadhesive strength (using texture analyzer and subjected to in vitro drug release studies. Real-time stability studies were also conducted on prepared batches. In vitro drug release data were fitted in various release kinetic models for studying the mechanism of drug release. Tensile strength was found to increase from 0.808 ± 0.098 to 1.527 ± 0.10 mN/cm 2 and mucoadhesive strength increased from 13.673 ± 1.542 to 40.378 ± 2.345 N, with an increase in the polymer concentration from 5 to 20% (A1 to A4. Swelling index was reported to increase with both increase in the concentration of gum and the time duration. The in vitro drug release decreased from 97.76 to 83.4% (A1 to A4 with the increase in polymer concentration. The drug release from the matrix tablets was found to follow zero-order and Higuchi models, indicating the matrix-forming potential of natural polymer. The value of n was found to be between 0.5221 and 0.8992, indicating the involvement of more than one drug release mechanism from the formulation and possibly the combination of both diffusion and erosion. These research findings clearly indicate the potential of S. plebeian gum to be used as binder, release retardant and mucoadhesive natural material in tablet formulations.

  18. Pharmacological and clinical evidence of nevirapine immediate- and extended-release formulations

    Directory of Open Access Journals (Sweden)

    Ena J

    2012-11-01

    Full Text Available Javier Ena, Concepción Amador, Conxa Benito, Francisco PasquauHIV Unit, Hospital Marina Baixa, Villajoyosa, SpainAbstract: We reviewed the current information available on nevirapine immediate- and extended-release formulations and its role in single-dose and combination antiretroviral therapy. Nevirapine was approved in 1996 and was the first non-nucleoside reverse-transcriptase inhibitor available for the treatment of HIV-1 infection. Nevirapine has demonstrated good efficacy and a well-characterized safety profile. A major drawback is the low genetic barrier, allowing the emergence of resistance in the presence of single mutations in the reverse-transcriptase gene. This shortcoming is particularly relevant when nevirapine is administered in a single dose to prevent mother-to-child transmission of HIV-1 infection, compromising the efficacy of future non-nucleoside reverse transcriptase–inhibitor regimens. Studies published recently have probed the noninferiority of nevirapine compared to ritonavir-boosted atazanavir with both tenofovir disoproxil fumarate and emtricitabine in antiretroviral treatment–naïve patients. In 2011, a new formulation of nevirapine (nevirapine extended release that allowed once-daily dosing was approved by the Food and Drug Administration and by the European Medicines Agency. VERxVe, a study comparing nevirapine extended release with nevirapine immediate release in antiretroviral treatment–naïve patients, and TRANxITION, a study carried out in antiretroviral treatment–experienced patients who switched therapy from nevirapine immediate release to nevirapine extended release, provided data on the noninferiority of the new formulation of nevirapine compared with nevirapine immediate release in terms of efficacy and safety. Nevirapine extended release will further increase the durability and persistence of nevirapine-containing antiretroviral therapy, allowing once-daily dosing regimens.Keywords: nevirapine

  19. Formulation and Mathematical Optimization of Controlled Release Calcium Alginate Micro Pellets of Frusemide

    OpenAIRE

    Amitava Ghosh; Prithviraj Chakraborty

    2013-01-01

    Objective. Frusemide loaded calcium alginate micropellets, an oral microparticulate delivery system, was statistically optimized exhibiting prolonged therapeutic action minimizing its adverse effects. Methods. Ionotropic Gelation technique was adopted employing 32 Factorial designs and keeping the entire process free from organic solvents. Physicochemical and the release characteristics of the prepared formulations were studied, keeping variations only in sodium alginate (primary polymer) and...

  20. 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.

  1. EFFECT OF FORMULATION VARIABLES ON THE RELEASE OF ACECLOFENAC FROM HPMC MATRIX TABLETS

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    S. R. Mettu

    2011-11-01

    Full Text Available The objective of this work was to study the effect of concentration and viscosity grade of HPMC, different diluents and inclusion of solid dispersions on the matrix tablets of aceclofenac. In present study, aceclofenac, a novel NSAID used for symptomatic treatment of pain and inflammation was formulated into matrix tablets with HPMC of two different viscosity grades (E50 LV and K15 M by direct compression method. Before compression the formulations were evaluated for angle of repose, % compressibility and Hausner’s ratio. Tablets were evaluated for hardness, friability, weight variation, uniformity of thickness and diameter, and drug content. All pre-compressional and post-compressional parameters were found within the official limits. In vitro drug release studies were conducted for a period of 8 hrs using USP paddle method (II at 37±0.5oC and at 75rpm speed in pH 7.2 phosphate buffer. Type of polymer and its concentration has influenced the drug release from matrix tablets. With increasing concentrations and increasing polymer viscosity the release rate decreased. Release rate increased with the addition of PEG and PVP. There was significant increase in drug release by inclusion of solid dispersions in the matrix tablets. It can be concluded that by incorporating water soluble excipients such as PEG and PVP and solid dispersions of drug with PVP into the matrix, drug release can be increased. Dissolution data was analysed by Power law expression, Mt / M¥ = ktn. Release of drug from the tablets varied on the basis of formulation and was found to be non-Fickian and case II transport with different formulations.

  2. Delayed ulnar neuropathy at the wrist following open carpal tunnel release.

    Science.gov (United States)

    Pingree, Matthew J; Bosch, E Peter; Liu, Patrick; Smith, Benn E

    2005-03-01

    Open carpal tunnel release is a common and successful treatment of median neuropathy at the wrist (carpal tunnel syndrome). We report a case of delayed ulnar neuropathy at the wrist with onset 2 months after open carpal tunnel release. Clinical findings, electrophysiological studies, magnetic resonance imaging, and surgical exploration demonstrated ulnar nerve compression at Guyon's canal resulting from translocation of the carpal tunnel contents. To our knowledge, this is an unreported complication of open carpal tunnel release that merits wide appreciation.

  3. Evaluation of in vitro release rate and in vivo absorption characteristics of four metoprolol tartrate immediate-release tablet formulations.

    Science.gov (United States)

    Rekhi, G S; Eddington, N D; Fossler, M J; Schwartz, P; Lesko, L J; Augsburger, L L

    1997-02-01

    The purpose of this investigation was to examine the impact of formulation and process changes on dissolution and bioavailability/bioequivalency of metoprolol tartrate tablets manufactured using a high-shear granulation process. A half-factorial (2(4-1), Res IV) design was undertaken to study the selected formulation and processing variables during scale-up. Levels and ranges for excipients and processing changes studied represented level 2 or greater changes as indicated by the SUPAC-IR Guidance. Blend and tableting properties were evaluated. Changes in sodium starch glycolate and magnesium stearate levels, and the order of addition microcrystalline cellulose (intra- vs. extragranular) were significant only in affecting percent drug released (Q) in 5, 10, and 15 min. Statistical analysis of data showed no significant curvature. No interaction effects were found to be statistically significant. To examine the impact of formulation and processing variables on in vivo absorption, three batches were selected for a bioavailability study based on their dissolution profiles. Subjects received four metoprolol treatments (Lopressor, slow-, medium-, and fast-dissolving formulations) separated by 1 week according to a randomized crossover design. After an overnight fast, subjects were administered one tablet (100 mg), blood samples were collected over 24 hr and plasma samples were analyzed. The formulations were found to be bioequivalent with respect to the log Cmax and log AUC0-infinity. The results of this study suggest that: (i) bioavailability/bioequivalency studies may not be necessary for metoprolol tartrate and perhaps other class 1 drugs after level 2 type changes and (ii) in vitro dissolution tests may be used to show bioequivalence of metoprolol formulations with processing or formulation changes within the specified level 2 ranges for the equipment examined.

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

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    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.

  5. Formulation and evaluation of modified-release effervescent floating tablets of ofloxacin

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    Sarat Chandra Prasad Malisetty

    2013-01-01

    Full Text Available Aims: Ofloxacin is used as anti-microbial agent. Due to its high solubility in gastric pH, a floating drug delivery system was selected to improve the bioavailability and therapeutic efficacy of the drug. Settings and Design: The purpose of the study was to prepare and evaluate effervescent floating tablets of ofloxacin to prolong its gastric residence and increase bioavailability. Materials and Methods: Drug, semi-synthetic and natural polymers, such as HPMC K4M, Guar gum, Xanthan gum and Chitosan, were used. Sodium bicarbonate and citric acid were used as gas-generating agents and tablet compression was done by direct compression. The prepared tablets were characterized and were evaluated for in vitro floating behavior, swelling index, in vitro drug release studies and release kinetics. Results: Formulation F6 containing xanthan gum and chitosan in a 1:1 ratio attained sustained release for 12 h and drug release observed was about 76.7%. Swelling index was in the range 62.17 ± 1.49% to 194.02 ± 1.05%. Floating lag time was observed in the range 4.11-6.26 min. Conclusion: The in vitro results showed better drug release conditions, supported by follow-up in vivo studies, suggesting that this formulation is advantageous over the current marketed formulation, through increased gastric residence and bioavailability.

  6. FORMULATION AND EVALUATION OF METOPROLOL SUCCINATE CONTROLLED RELEASE TABLETS USING NATURAL AND SYNTHETIC POLYMER

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    A. Sathyaraj

    2012-01-01

    Full Text Available The objective of the present study to develop controlled release tablets of Metoprolol succinate using Natural polymer, guar gum and synthetic polymer, carbopol as a rate controlling polymers.. It was also desired to study the effect of polymer concentration. Metoprolol succinate, β1- selective adrenergic receptor- blocking agent used in the management of hypertension, angina pectoris, cardiac arrthymias, myocardial infarction, heart failure, hyperthyroidism and in the prophylactic treatment of migraine. The half-life of drug is relatively short approximately 4-6 hrs and in normal course of therapy drug administration is required every 4-6 hrs, thus warrants the use of controlled release formulation for prolong action and to improve patient compliance. In the present investigation Natural polymer, guar gum and synthetic polymer, carbopol have been selected as matrix forming materials for the drug. The formulations are made by employing the conventional wet granulation method, to achieve prolonged release of medicaments.

  7. Report of two cases where sleep related eating behavior occurred with the extended-release formulation but not the immediate-release formulation of a sedative-hypnotic agent.

    Science.gov (United States)

    Chiang, Ambrose; Krystal, Andrew

    2008-04-15

    We report two cases in which amnestic sleep related eating disorder (SRED) occurred with extended-release zolpidem but not with the immediate-release formulation. These cases illustrate how even relatively small differences such as formulation can affect the likelihood of experiencing such events.

  8. Therapeutic Efficacy of pH-Dependent Release Formulation of Mesalazine on Active Ulcerative Colitis Resistant to Time-Dependent Release Formulation: Analysis of Fecal Calprotectin Concentration

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    Kousaku Kawashima

    2014-01-01

    Full Text Available Purpose. Few reports have compared the clinical efficacy of a pH-dependent release formulation of mesalazine (pH-5-ASA with a time-dependent release formulation (time-5-ASA. We examined whether pH-5-ASA is effective for active ulcerative colitis (UC in patients resistant to time-5-ASA. Methods. We retrospectively and prospectively analyzed the efficacy of pH-5-ASA in mildly to moderately active UC patients in whom time-5-ASA did not successfully induce or maintain remission. The clinical efficacy of pH-5-ASA was assessed by clinical activity index (CAI before and after switching from time-5-ASA. In addition, the efficacy of pH-5-ASA on mucosal healing (MH was evaluated in a prospective manner by measuring fecal calprotectin concentration. Results. Thirty patients were analyzed in a retrospective manner. CAI was significantly reduced at both 4 and 8 weeks after switching to pH-5-ASA. In the prospective study (n=14, administration of pH-5-ASA also significantly reduced CAI scores at 4 and 8 weeks in these patients who were resistant to time-5-ASA. In addition, fecal calprotectin concentration was significantly decreased along with improvement in CAI after switching to pH-5-ASA. Conclusions. Our results suggest that pH-5-ASA has clinical efficacy for mildly to moderately active patients with UC in whom time-5-ASA did not successfully induce or maintain remission.

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

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    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.

  10. Influence of metoprolol dosage release formulation on the pharmacokinetic drug interaction with paroxetine.

    Science.gov (United States)

    Stout, Stephen M; Nielsen, Jace; Welage, Lynda S; Shea, Michael; Brook, Robert; Kerber, Kevin; Bleske, Barry E

    2011-03-01

    Studies have demonstrated an influence of dosage release formulations on drug interactions and enantiomeric plasma concentrations. Metoprolol is a commonly used beta-adrenergic antagonist metabolized by CYP2D6. The CYP2D6 inhibitor paroxetine has previously been shown to interact with metoprolol tartrate. This open-label, randomized, 4-phase crossover study assessed the potential differential effects of paroxetine on stereoselective pharmacokinetics of immediate-release (IR) tartrate and extended-release (ER) succinate metoprolol formulations. Ten healthy participants received metoprolol IR (50 mg) and ER (100 mg) with and without paroxetine coadministration. Blood samples were collected over 24 hours for determination of metoprolol plasma enantiomer concentrations. Paroxetine coadministration significantly increased S and R metoprolol area under the plasma concentration-time curve from time 0 to the 24-hour blood draw (AUC(0-24h)) by 4- and 5-fold, respectively for IR, and 3- and 4-fold, respectively, for ER. S/R AUC ratios significantly decreased. These results demonstrate a pharmacokinetic interaction between paroxetine and both formulations of metoprolol. The interaction is greater with R metoprolol, and stereoselective metabolism is lost. This could theoretically result in greater beta-blockade and lost cardioselectivity. The magnitude of the interaction was similar between metoprolol formulations, which may be attributable to low doses/drug input rates employed.

  11. FORMULATION AND EVALUATION OF EXTENDED RELEASE MATRIX TABLETS OF TRIMETAZIDINE DIHYDROCHLORIDE

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    Mogili Dinesh

    2013-01-01

    Full Text Available Oral ingestion has long been the most convenient and commonly employed route of drug delivery. Indeed, for Extended release systems, the oral route of administration has by far received the most attention with respect to research on physiological and drug constraints as well as design and testing of products. The primary objective of the extended release (Matrix drug delivery system is to ensure safety and to improve efficacy of drug as well as patient compliance. The present invention provides a novel sustained release composition comprising Trimetazidine Dihydrochloride. The objective of the present study was to formulate and evaluate once daily extended release matrix tablets of Trimetazidine Dihydrochloride using hydrophilic polymers Hydroxypropylmethylcellulose, Polyox, and natural polymer Xanthan gum. Trimetazidine has a half life 6 hrs and usual oral dosage regimen 0.5 mg and 60 mg daily. To reduce the frequency of administration and to improve patient compliance, a once-daily extended release formulation of Trimetazidine is desirable. The most commonly used method of modulating the drug release is to include it in a matrix system. Hydrophilic polymer matrix systems were widely used in oral controlled drug delivery because they make it easier to achieve a desirable drug-release profile, they are cost effective and they have broad US Food and Drug Administration acceptance. Hence, in present work, an attempt has been made to develop once daily sustained release matrix tablets of Trimetazidine using putative hydrophilic matrix materials. The drug release for extended duration using a hydrophilic matrix system is restricted because of rapid diffusion of dissolved drug through the hydrophilic gel network.

  12. Formulation effects on the release of silica dioxide nanoparticles from paint debris to water.

    Science.gov (United States)

    Zuin, Stefano; Massari, Andrea; Ferrari, Arlen; Golanski, Luana

    2014-04-01

    Waterborne paints with integrated nanoparticles have been recently introduced into the market as nanoparticles offer improved or novel functionalities to paints. However, the release of nanoparticles during the life cycle of nano-enhanced paint has only been studied to a very limited extent. The paint composition could determine in what quantities and forms the nanoparticles are released. In this work, paint formulations containing the same amount of silicon dioxide (SiO2) nanoparticles but differing in the pigment volume concentration (PVC) and in amount and type of binder and pigment, were studied through leaching test to investigate the influence of these parameters on release of Si from paint. The results indicate greater release of Si, about 1.7 wt.% of the SiO2 nanoparticles in the paint, for paint formulated with higher PVC value (63%), suggesting that the PVC is a crucial factor for release of SiO2 nanoparticles from paints. This hypothesis was also based on the fact that agglomerates of SiO2 nanoparticles were only found in leachates from paint with higher PVC. A paint sample with the higher amount of binder and less calcite filler exhibited a lower release of Si among the paints with a low PVC value (35%), and no SiO2 particles were detected in leachates collected from this paint. This could be due to the fact that a high portion of binder forms a suitable matrix to hold the SiO2 ENPs in paint. The paint sample in which the amount of calcite was partially substituted with TiO2 pigment did not show an important reduction on Si release. Our work suggests that paint debris containing SiO2 nanoparticles may release a limited amount of Si into the environment, and that by adjusting the properties of the binder in combination with common pigments it is possible to reduce the release of SiO2 nanoparticles.

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

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    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.

  14. Polymeric macroporous formulations for the control release of mosquitocidal Bacillus sphaericus ISPC-8.

    Science.gov (United States)

    Tripathi, Anuj; Hadapad, Ashok B; Hire, Ramesh S; Melo, Jose S; D'Souza, Stanislaus F

    2013-12-10

    Bio-polymeric mosquitocidal formulations were developed for the control release of Bacillus sphaericus ISPC-8 by the immobilization of its spore-crystal complex onto the macroporous polymeric matrices. The biodegradable formulations were synthesized at sub-zero temperature using natural polymeric substrates like agarose, alginate, cellulose, non-adsorbent cotton, wooden cork powder and also magnetite nanoparticles. The obtained polymeric matrices were morphologically characterized, which showed 85-90% porosity, uniform pores distribution, high permeability and controlled degradation (19-30%) in 4 weeks depending upon the composition of formulations. Further, the polymeric macroporous formulations were tested for persistence of mosquitocidal activity against Culex quinquefasciatus larvae. Unformulated B. sphaericus ISPC-8 spores retained 54% of larvicidal activity after 7 days, which completely reduced after 35 days of treatment. However, the immobilized B. sphaericus spores in agarose-alginate formulations showed high larvicidal activity on day 7 and retained about 45% activity even after 35 days of treatments. Studies on UV-B and pH dependent inactivation of toxins and spore viability showed that these formulations were significantly protecting the spores as compared to the unformulated spores, which suggest its potential application for the mosquito control program.

  15. Differential scanning calorimetry as a screening technique in compatibility studies of acyclovir extended release formulations

    Energy Technology Data Exchange (ETDEWEB)

    Barboza, Fernanda M.; Vecchia, Debora D. [Universidade Estadual de Ponta Grossa (UEPG), PR (Brazil). Dept. de Ciencias Farmaceuticas. Lab. de Controle de Qualidade; Tagliari, Monika P.; Ferreira, Andrea Granada; Silva, Marcos A.S.; Stulzer, Hellen K., E-mail: hellen.stulzer@gmail.co [Universidade Federal de Santa Catarina (UFSC), Florianopolis, SC (Brazil). Dept. de Ciencias Farmaceuticas. Lab. de Controle de Qualidade

    2009-07-01

    Acyclovir (ACV) has been investigated during the past years, mainly due to its antiviral activity. Assessment of possible incompatibility between an active component and different excipients along with the evaluation of thermal stability are crucial parts of a normal study prior to the final formulation setting of a medicine. Thermal analysis studies were used as important and complementary tools during pre-formulation to determine the compatibility of drug excipients with the purpose of developing an acyclovir extended release formulation. Fourier transform infrared spectroscopy and X-ray powder diffraction analyses were also realized. The results showed that ACV only exhibited interaction which could influence the stability of the product in the binary mixtures of ACV/magnesium stearate. (author)

  16. 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

  17. Formulation and evaluation of press coated tablets of salbutamol sulphate for time controlled release

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    M D Wasimul Hasan

    2014-01-01

    Full Text Available The objective of the present study was to formulate and evaluate a press coated pulsatile drug delivery system of salbutamol sulphate in order to attain a time controlled release for treatment of nocturnal asthma. The core was prepared by direct compression, while press coating technique was used in coating the outer layer there by preparing a press coated tablet. The immediate release core formulations comprised of salbutamol sulphate and disintegrants like crospovidone, croscarmellose sodium and sodium starch glycolate in different ratios with the drug. The outer coat formulations were prepared using a hydrophilic (HPMC and hydrophobic (EC polymer of similar viscosity. The polymers were reviewed individually for their influence on lag time further obtaining the lag time using polymer combinations were assessed by employing central composite design. All the preliminary trials were evaluated for various post compression parameters along with the dissolution study that was performed using USP paddle method at 50 rpm in 0.1 N HCl and phosphate buffer pH 6.8. The formulation containing 300 mg of EC N50 and 75-100 mg of HPMC E50 may be regarded as the minimum quantity required in outer press coat so as to attain a predetermined lag time of 6 h.

  18. PLGA biodegradable nanoparticles containing perphenazine or chlorpromazine hydrochloride: effect of formulation and release.

    Science.gov (United States)

    Halayqa, Mohammed; Domańska, Urszula

    2014-12-22

    In our study, poly(dl-lactide-co-glycolide) (PLGA) nanoparticles loaded with perphenazine (PPH) and chlorpromazine hydrochloride (CPZ-HCl) were formulated by emulsion solvent evaporation technique. The effect of various processing variables, including PLGA concentration, theoretical drug loading, poly(vinyl alcohol) (PVA) concentration and the power of sonication were assessed systematically to obtain higher encapsulation efficiency and to minimize the nanoparticles size. By the optimization formulation process, the nanoparticles were obtained in submicron size from 325.5 ± 32.4 to 374.3 ± 10.1 nm for nanoparticles loaded with PPH and CPZ-HCl, respectively. Nanoparticles observed by scanning electron microscopy (SEM) presented smooth surface and spherical shape. The encapsulation efficiency of nanoparticles loaded with PPH and CPZ-HCl were 83.9% and 71.0%, respectively. The drug loading were 51.1% and 39.4% for PPH and CPZ-HCl, respectively. Lyophilized nanoparticles with different PLGA concentration 0.8%, 1.3% and 1.6% (w/v) in formulation process were evaluated for in vitro release in phosphate buffered saline (pH = 7.4) by using dialysis bags. The release profile for both drugs have shown that the rate of PPH and CPZ-HCl release were dependent on a size and amount of drugs in the nanoparticles.

  19. PLGA Biodegradable Nanoparticles Containing Perphenazine or Chlorpromazine Hydrochloride: Effect of Formulation and Release

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    Mohammed Halayqa

    2014-12-01

    Full Text Available In our study, poly(dl-lactide-co-glycolide (PLGA nanoparticles loaded with perphenazine (PPH and chlorpromazine hydrochloride (CPZ-HCl were formulated by emulsion solvent evaporation technique. The effect of various processing variables, including PLGA concentration, theoretical drug loading, poly(vinyl alcohol (PVA concentration and the power of sonication were assessed systematically to obtain higher encapsulation efficiency and to minimize the nanoparticles size. By the optimization formulation process, the nanoparticles were obtained in submicron size from 325.5 ± 32.4 to 374.3 ± 10.1 nm for nanoparticles loaded with PPH and CPZ-HCl, respectively. Nanoparticles observed by scanning electron microscopy (SEM presented smooth surface and spherical shape. The encapsulation efficiency of nanoparticles loaded with PPH and CPZ-HCl were 83.9% and 71.0%, respectively. The drug loading were 51.1% and 39.4% for PPH and CPZ-HCl, respectively. Lyophilized nanoparticles with different PLGA concentration 0.8%, 1.3% and 1.6% (w/v in formulation process were evaluated for in vitro release in phosphate buffered saline (pH = 7.4 by using dialysis bags. The release profile for both drugs have shown that the rate of PPH and CPZ-HCl release were dependent on a size and amount of drugs in the nanoparticles.

  20. Development and Optimization of a Novel Prolonged Release Formulation to Resist Alcohol-Induced Dose Dumping.

    Science.gov (United States)

    Gujjar, Chaitanya Yogananda; Rallabandi, Balaramesha Chary; Gannu, Ramesh; Deulkar, Vallabh Subashrao

    2016-04-01

    Alcohol-induced dose dumping is a serious concern for the orally administered prolonged release dosage forms. The study was designed to optimize the independent variables, propylene glycol alginate (PGA), Eudragit RS PO (ERS) and coating in mucoadhesive quetiapine prolonged release tablets 200 mg required for preventing the alcohol-induced dose dumping. Optimal design based on response surface methodology was employed for the optimization of the composition. The formulations are evaluated for in vitro drug release in hydrochloric acid alone and with 40% v/v ethanol. The responses, dissolution at 120 min without alcohol (R1) and dissolution at 120 min with alcohol (R2), were statistically evaluated and regression equations are generated. PGA as a hydrophilic polymeric matrix was dumping the dose when dissolutions are carried in 0.1 N hydrochloric acid containing 40% v/v ethanol. ERS addition was giving structural support to the swelling and gelling property of PGA, and thus, was reducing the PGA erosion in dissolution media containing ethanol. Among the formulations, four formulations with diverse composition were meeting the target dissolution (30-40%) in both the conditions. The statistical validity of the mathematical equations was established, and the optimum concentration of the factors was established. Validation of the study with six confirmatory runs indicated high degree of prognostic ability of response surface methodology. Further coating with ReadiLycoat was providing an additional resistance to the alcohol-induced dose dumping. Optimized compositions showed resistance to dose dumping in the presence of alcohol.

  1. Ethanol effects on drug release from Verapamil Meltrex, an innovative melt extruded formulation.

    Science.gov (United States)

    Roth, W; Setnik, B; Zietsch, M; Burst, A; Breitenbach, J; Sellers, E; Brennan, D

    2009-02-23

    The potential effect of ethanol to accelerate drug release from sustained release (SR) oral formulations is a general concern. Marketed Verapamil is a calcium channel blocker, mainly used as antihypertensive and anti-anginal drug and available in various dose and dosage forms. One is Verapamil Meltrex, combining an innovative and unique SR formulation and technology that achieves a stable solid dispersion of drug by using melt extrusion technology. The aim of this investigation was to determine the influence of ethanol on the in vitro rate of release of marketed Verapamil (240 mg) Meltrex, in contrast to three compressed marketed Verapamil (240 mg) SR formulations. Dissolution was tested under standardized conditions, with mediums containing ethanol concentrations of 0, 5, 20, and 40%. The dissolution profiles for Verapamil Meltrex showed no differences between 5 and 40% ethanol versus 0% ethanol (P>0.05). The mean dissolution percentage (%) was identical at 1h (19%) in 0% versus 40% ethanol. In contrast, the three comparators showed significant increases in dissolution in 20 and 40% ethanol versus 0% ethanol (Pdose dumping when combined with readily accessible ethanol concentrations.

  2. Risk based in vitro performance assessment of extended release abuse deterrent formulations.

    Science.gov (United States)

    Xu, Xiaoming; Gupta, Abhay; Al-Ghabeish, Manar; Calderon, Silvia N; Khan, Mansoor A

    2016-03-16

    High strength extended release opioid products, which are indispensable tools in the management of pain, are associated with serious risks of unintentional and potentially fatal overdose, as well as of misuse and abuse that might lead to addiction. The issue of drug abuse becomes increasingly prominent when the dosage forms can be readily manipulated to release a high amount of opioid or to extract the drug in certain products or solvents. One approach to deter opioid drug abuse is by providing novel abuse deterrent formulations (ADF), with properties that may be viewed as barriers to abuse of the product. However, unlike regular extended release formulations, assessment of ADF technologies are challenging, in part due to the great variety of formulation designs available to achieve deterrence of abuse by oral, parenteral, nasal and respiratory routes. With limited prior history or literature information, and lack of compendial standards, evaluation and regulatory approval of these novel drug products become increasingly difficult. The present article describes a risk-based standardized in-vitro approach that can be utilized in general evaluation of abuse deterrent features for all ADF products.

  3. Formulation and evaluation of controlled release floating matrix tablets of Stavudine

    Directory of Open Access Journals (Sweden)

    Suryadevara Vidyadhara

    2012-01-01

    Full Text Available The purpose of this research was to prepare and evaluate floating drug delivery systems of Stavudine. Floating matrix tablets of Stavudine were developed to prolong gastric residence time and increase its bioavailability. Rapid gastrointestinal transit could result in incomplete drug release from the drug delivery system above the absorption zone leading to diminished efficacy of the administered dose. The matrix tablets were prepared by direct compression technique, using polymers such as hydroxylpropylmethyl cellulose (HPMC K15M, karaya gum and other standard excipients. Sodium bicarbonate was incorporated as a gas-generating agent. The effect of different concentrations of polymers on drug release profile and floating properties were investigated. Comparable release profiles between the commercial product and the designed system were obtained. The matrix formulations were evaluated for physical parameters, drug release by in vitro dissolution studies and in vitro buoyancy studies. Surface characteristics, drug-excipient interactions and crystal morphology of optimized formulations were evaluated by SEM analysis and DSC studies.

  4. Safety and efficacy considerations due to misuse of extended-release formulations of stimulant medications.

    Science.gov (United States)

    Jain, Rakesh; Stark, Jeffrey G

    2016-09-01

    Amphetamine or methylphenidate are first-line options for treating attention-deficit/hyperactivity disorder (ADHD). Deviations from suggested routes of administration such as crushing, chewing, intravenous administration, or snorting stimulant medication may alter the release rate, absorption, and bioavailability of the active drug. Additionally, the pharmacokinetic (PK) profiles of extended-release formulations of certain medications (e.g., some opioids) are known to be dangerously altered when consumed with alcohol; specifically, there is an unintended, rapid release of a significant portion of the drug (dose dumping). In vitro data suggest some extended-release stimulants dose dump in the presence of alcohol, which is of concern because the ADHD patient population is at risk for alcohol abuse. This article reviews the available scientific literature concerning modifications to routes of administration that may alter PK properties of stimulant-based medication for treating ADHD. These modifications are of clinical interest because they may pose safety hazards and affect efficacy. Electronic databases were searched for appropriate studies using relevant search terms. The misuse and abuse potential for stimulants and the efforts to prevent misuse are also discussed. Future research should be focused on determining the PK ramifications of stimulant misuse, along with developing new formulations with abuse-deterrent properties.

  5. Pharmacokinetics study of extended release formulations of buspirone hydrochloride in Beagle dogs

    Institute of Scientific and Technical Information of China (English)

    CUI Meng-cun; LI Jing-lai; CHEN Yan; WANG Xiao-ying; QIAO Jian-zhong; ZHANG Zhen-qing; RUAN Jin-xiu

    2008-01-01

    Objective To evaluate the pharmacokinetics (PK) properties of extended release formulations of buspirone hydrochloride in Beagle dogs. Methods A randomized, two period, two treatment, two sequence crossover bioequivalenee study was designed; six healthy Beagle dogs were randomly divided into two groups, each group was orally given buspirone tablets or buspirone extended capsule containing 15 mg buspirone hydrochloride. Blood samples (about 1 mL) were collected in heparinized tubes before dosing and at 0.33, 0.67, 1,2, 3, 4, 6, 8, 10, 12, 18, 24 h after administration, and were then immediately centrifuged at 3000 rpm for 15 min. The pharmacokinetics (PK) properties of the drugs were evaluated using the liquid chromatographic-tandem mass spectrometric (LC-MS/MS) method. Results The mean tmax was 4.7, 0.8 h and Cmax values was 1.8, 6.9 μg·L-1, respectively for the sustained-release test (capsule) and reference formulation (tablet). When compared to the tablets, the residence time of the sustained capsules was dramatically prolonged and Cmax Was reduced (P<0.01). The initial release speed was slow and stable. The bioavailability was similar to the common tablets. Conclusions The sustained capsule had showed good pharmacokinetics property of sustained-release in the Beagle dogs.

  6. Release kinetics of controlled release formulations of thiamethoxam employing nano-ranged amphiphilic PEG and diacid based block polymers in soil.

    Science.gov (United States)

    Sarkar, Dhruba Jyoti; Kumar, Jitendra; Shakil, N A; Walia, S

    2012-01-01

    Amphiphilic copolymers, synthesized from poly(ethylene glycols) and various aliphatic and aromatic diacids, which self-assemble into nanomicellar aggregates in aqueous media, were used to develop controlled release (CR) formulations of thiamethoxam (3-(2-chloro-1,3-thiazol-5-ylmethyl)-5-methyl-1,3,5-oxadiazinan-4-ylidene(nitro)amine) using encapsulation technique Formulations were characterised by Infrared (IR) spectroscopy, Dynamic Light Scattering (DLS) and Transmission Electron Microscope (TEM). Encapsulation efficiency, loading capacity and stability after accelerated storage test of the developed formulations were checked. The kinetics of thiamethoxam, released in sandy loam soil from the different formulations was studied. Release from the commercial formulation was faster than the CR formulations. The time taken for release of 50 % of thiamethoxam ranged from 3.56 to 6.07 days for the CR formulations. Although the diffusion exponent (n value) of thiamethoxam in soil ranged from 0.532 to 0.881 in the tested formulations showing non-Fickian transport. These CR formulations may be used in safer, effective and economic crop protection.

  7. Effect of xanthan gum on the release of strawberry flavor in formulated soy beverage.

    Science.gov (United States)

    Xu, Jiao; He, Zhiyong; Zeng, Maomao; Li, Bingbing; Qin, Fang; Wang, Linxiang; Wu, Shengfang; Chen, Jie

    2017-08-01

    The effects of xanthan gum on the release of strawberry flavor compounds in formulated soy protein isolate (SPI) beverage were investigated by headspace gas chromatography (GC). Seven strawberry flavor compounds (limonene, ethyl hexanoate, (Z)-3-hexenyl acetate, ethyl 2-methylbutanoate, ethyl butanoate, (Z)-3-hexen-1-ol and diacetyl) could be detected by GC and hence analyzed the gas-matrix partition coefficients (K). The release of flavor compounds was restrained in SPI and/or xanthan gum solution. The retention of (Z)-3-hexen-1-ol, limonene and diacetyl significantly changed (pdecalactone, methyl cinnamate, hexanoic acid, 2-methyl butyric acid and furaneol) accelerated the release of ester compounds to some extent in different matrices. The above results demonstrated that presence of SPI and xanthan gum could bring about an imbalance in the strawberry flavor. Copyright © 2017 Elsevier Ltd. All rights reserved.

  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. Mathematical Model-Based Accelerated Development of Extended-release Metformin Hydrochloride Tablet Formulation.

    Science.gov (United States)

    Chen, W; Desai, D; Good, D; Crison, J; Timmins, P; Paruchuri, S; Wang, J; Ha, K

    2016-08-01

    A computational fluid dynamic (CFD) model was developed to predict metformin release from a hydroxypropylmethylcellulose (HPMC) matrix-based extended-release formulation that took into consideration the physical and chemical properties of the drug substance, composition, as well as size and shape of the tablet. New high dose strength (1000 mg) tablet geometry was selected based on the surface area/volume (SA/V) approach advocated by Lapidus/Lordi/Reynold to obtain the desired equivalent metformin release kinetics. Maintaining a similar SA/V ratio across all extended-release metformin hydrochloride (Met XR) tablet strengths that had different geometries provided similar simulations of dissolution behavior. Experimental dissolution profiles of three lots of high-strength tablets agreed with the simulated release kinetics. Additionally, a pharmacokinetic absorption model was developed using GastroPlus™ software and known physicochemical, pharmacokinetic, and in vitro dissolution properties of metformin to predict the clinical exposure of the new high strength (1000 mg) tablet prior to conducting a human clinical bioequivalence study. In vitro metformin release kinetics were utilized in the absorption model to predict exposures in humans for new 1000-mg Met XR tablets, and the absorption model correctly projected equivalent in vivo exposure across all dose strengths. A clinical bioequivalence study was pursued based on the combined modeling results and demonstrated equivalent exposure as predicted by the simulations.

  10. Influence of paints formulations on nanoparticles release during their life cycle

    Energy Technology Data Exchange (ETDEWEB)

    Fiorentino, Brice, E-mail: brice.fiorentino@cea.fr; Golanski, Luana; Guiot, Arnaud; Damlencourt, Jean-François; Boutry, Delphine [Commissariat à l’énergie atomique et aux énergies alternatives (France)

    2015-03-15

    Pristine nanoparticles (NPs) may present a hazard to humans and the environment, and hence it is important to know to what extent NPs can be freely released from commercialized products in which they are added. The purpose of this study was to identify the parameters of the paint formulation containing SiO{sub 2} NPs of 19-nm diameter that could have an impact on the release induced by aging and abrasion. In order to simulate outdoor aging during the life cycle of the product, painted panels were exposed to accelerated weathering experiments in accordance with the norm EN ISO 16474-3:2013. The surface modification of these paints was characterized by scanning electron microscope coupled with energy dispersive spectrometry (SEM–EDS). These analyses showed that the acrylic copolymer binder has undergone a more significant chemical degradation compared with the styrene-acrylic copolymer. To simulate a mechanical aging, abrasion tests were conducted using a Taber Abraser, simulating critical scenarios of the abrasion standard. The particle size distributions and particle concentrations of the abraded particles were measured using an electric low-pressure impactor. After accelerated aging and abrasion tests, we observed a link between the paint degradations occurring with the release of pristine NPs and the embedded pristine NPs. Surface degradation of acrylic copolymer paints was more significant than that of the styrene-acrylic copolymer paints, and this induced a release of NPs 2.7 times higher. Other parameters like TiO{sub 2} addition as pigments induced a strong stability of paint against light and water, decreasing the total number of NPs released from paints from 30,000 to 1200 particles/cm{sup 3}. These results revealed that formulations can be tuned to decrease the number of free NPs released and get a “safe-by-design” product.

  11. Identification of critical formulation and processing variables for metoprolol tartrate extended-release (ER) matrix tablets.

    Science.gov (United States)

    Rekhi, G S; Nellore, R V; Hussain, A S; Tillman, L G; Malinowski, H J; Augsburger, L L

    1999-06-02

    The objective of this study, was to examine the influence of critical formulation and processing variables as described in the AAPS/FDA Workshop II report on scale-up of oral extended-release dosage forms, using a hydrophilic polymer hydroxypropyl methylcellulose (Methocel K100LV). A face-centered central composite design (26 runs+3 center points) was selected and the variables studied were: filler ratio (lactose:dicalcium phosphate (50:50)), polymer level (15/32.5/50%), magnesium stearate level (1/1.5/2%), lubricant blend time (2/6/10 min) and compression force (400/600/800 kg). Granulations (1.5 kg, 3000 units) were manufactured using a fluid-bed process, lubricated and tablets (100 mg metoprolol tartrate) were compressed on an instrumented Manesty D3B rotary tablet press. Dissolution tests were performed using USP apparatus 2, at 50 rpm in 900 ml phosphate buffer (pH 6.8). Responses studied included percent drug released at Q1 (1 h), Q4, Q6, Q12. Analysis of variance indicated that change in polymer level was the most significant factor affecting drug release. Increase in dicalcium phosphate level and compression force were found to affect the percent released at the later dissolution time points. Some interaction effects between the variables studied were also found to be statistically significant. The drug release mechanism was predominantly found to be Fickian diffusion controlled (n=0.46-0.59). Response surface plots and regression models were developed which adequately described the experimental space. Three formulations having slow-, medium- and fast-releasing dissolution profiles were identified for a future bioavailability/bioequivalency study. The results of this study provided the framework for further work involving both in vivo studies and scale-up.

  12. Extended release matrix tablets of Stavudine: Formulation and in vitro evaluation

    Directory of Open Access Journals (Sweden)

    Saravanakumar M

    2010-01-01

    Full Text Available During the past two decades, there has been a steady increase in both the number of antiretroviral medications and the number of possible regimens available to manage human immunodeficiency virus (HIV and acquired immune deficiency syndrome (AIDS. But still, regimen fails due to some reasons such as toxicity, adverse effects, and consequent difficulties with patient adherence. Stavudine is the Food and Drug Administration approved drug for clinical use for the treatment of HIV infection, AIDS, and AIDS related conditions, either alone or in combination with other antiviral agents. The side effects of Stavudine are dose dependent and a reduction of the total administered dose reduces the severity of the toxicity. To reduce the frequency of administration and to improve patient compliance, a once daily sustained release formulation of Stavudine is desirable. Hence, in the present work, an attempt has been made to develop once daily sustained release matrix tablets of Stavudine using putative hydrophilic matrix materials such as hydroxyl propyl methyl cellulose (HPMC K4M and Carbopol 974P. The prepared extended release tablets were then evaluated for various physical tests like diameter, thickness, weight variation, hardness, friability, and drug content uniformity. The results of all these tests were found to be satisfactory. Formulation F9 extended the drug release till the end of 24 hours and showed higher r values for zero order plot, indicating that drug release followed zero order kinetics. This finding reveals that above a particular concentration, HPMC K4M and Carbopol 974P are capable of providing almost zero order drug release.

  13. Differential acetylcholine release in the prefrontal cortex and hippocampus during pavlovian trace and delay conditioning.

    Science.gov (United States)

    Flesher, M Melissa; Butt, Allen E; Kinney-Hurd, Brandee L

    2011-09-01

    Pavlovian trace conditioning critically depends on the medial prefrontal cortex (mPFC) and hippocampus (HPC), whereas delay conditioning does not depend on these brain structures. Given that the cholinergic basal forebrain system modulates activity in both the mPFC and HPC, it was reasoned that the level of acetylcholine (ACh) release in these regions would show distinct profiles during testing in trace and delay conditioning paradigms. To test this assumption, microdialysis probes were implanted unilaterally into the mPFC and HPC of rats that were pre-trained in appetitive trace and delay conditioning paradigms using different conditional stimuli in the two tasks. On the day of microdialysis testing, dialysate samples were collected during a quiet baseline interval before trials were initiated, and again during performance in separate blocks of trace and delay conditioning trials in each animal. ACh levels were quantified using high-performance liquid chromatography and electrochemical detection techniques. Consistent with our hypothesis, results showed that ACh release in the mPFC was greater during trace conditioning than during delay conditioning. The level of ACh released during trace conditioning in the HPC was also greater than the levels observed during delay conditioning. While ACh efflux in both the mPFC and HPC selectively increased during trace conditioning, ACh levels in the mPFC during trace conditioning testing showed the greatest increases observed. These results demonstrate a dissociation in cholinergic activation of the mPFC and HPC during performance in trace but not delay appetitive conditioning, where this cholinergic activity may contribute to attentional mechanisms, adaptive response timing, or memory consolidation necessary for successful trace conditioning.

  14. Optimization and Validation of Modulated Release Formulation of Ranitidine HCl by Response Surface Methodology

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    Bijay Kumar Sahoo

    2011-01-01

    Full Text Available The objective of the present study was, 1 to systematically device a model of factors that would yield an optimized sustained release dosage form of model drug (Ranitidine HCl, 2 to validate the models using R2 values, 3 to optimize the formulation by response surface methodology (RSM. A three - factor, three - level Box-Behnken design was used for the optimization procedure, with the amounts of HPMC K100M (X1, MCC (X2 and Compression Force (X3 as independent variables. Three dependent variables were considered: percentage of drug release at 1 h, 12 h and T50%. The regression equation obtained from experiment i. e Y2 = 92.41 + 3.18X1+ 2.05 X2 + 2.14X3 + 2.41X1X2 + 0.24 X1X3 + 0.11 X2X3 -3.82X12 - 2.59X22 -0.46X32 , explained the main and interaction effects of factors that influenced the drug release. Optimization was performed by maximizing the drug release in 12 hrs and placing constraints on Y1, Y2 and Y3. Validation of optimization by carrying out by performing 8 experimental runs showed high degree of prognostic ability of response surface methodology. The results showed that the optimized formulation provided a dissolution pattern similar to the predicted curve, which indicated that the optimal formulation could be obtained using RSM. A simple high performance liquid chromatography method was developed and the dissolution samples were analysed by this procedure.

  15. Controlled release formulations of Atrazine and Mesotrione: characterization and sorption on soils

    Science.gov (United States)

    Pinheiro Dick, D.; Gomes de Ávila, L.; Benvenuti Leite, S.; Raffin Pohlmann, A.

    2009-04-01

    Atrazine is a widely used herbicide on corn and sugar cane plantations, which, along with soybeans, are the most productive crops in Brazil and are responsible for 36.5% of the annual national consumption of herbicides. Mesotrione is a new herbicide registered in the last years used for controlling weeds in corn plantations as a tentative substitution for atrazine. After its application in the field, reactions between the herbicide and chemical groups from the soil matrix surface occur, and this complexed form remains in the soil, representing a potential source for environmental contamination and also affecting its agronomic efficiency. Therefore, the application of herbicides associated to carrier systems may represent an alternative to mitigate the environmental impact caused by their intense usage, considering that the interaction between the soil matrix and the xenobiotic is reduced, and thus, diminishes the recommended dosis and reduces the environmental pollution. The objectives of this study are to evaluate the chemical and morphological characteristics of controlled release formulations of atrazine (ATZ) and of mesotrione (MES) and to investigate their sorptive behavior in three representative Brazilian soils. To assess the feasibility of using these associated systems, four formulations (SGATZ) containing different concentrations of atrazine and four formulations (SGMES) containing different levels of mesotrione (MES) were synthesized by the sol-gel method (SG), using tetraetil-ortho-silicate as precursor and NaF as catalyst. The formulations were characterized by elemental analysis, adsorption and desorption isotherms of nitrogen, thermal analysis (DSC), scanning electron microscopy (SEM) and infrared spectroscopy (FTIR). For comparison, samples of pure xerogel (SG), commercial MES (Callisto-Syngenta), pure ATZ (99% of active principle, Milênia), granulated ATZ (Gesaprim GrDA Syngenta) and dried commercial ATZ (Nortox 500 SC) were analyzed. The

  16. FORMULATION AND EVALUATION OF ZIDOVUDINE CONTROLLED RELEASE GAS POWERED SYSTEM USING HYDROPHILLIC POLYMER

    Directory of Open Access Journals (Sweden)

    N. G. Raghavendra Rao

    2011-03-01

    Full Text Available Zidovudine is the first approved compound for the treatment of AIDS; however the main limitation to therapeutic effectiveness of zidovudine is its dose-dependent toxicity, short biological half-life and poor bioavailability. The present research work an attempt has been made to develop the Zidovudine gas powered drug delivery system for controlled release. The Zidovudine gas powered tablets were prepared by direct compression method by using the different grades of hydrophilic polymer like HPMC. The sodium bicarbonates and citric acid were also used as a gas generating agent. The power blend was subjected for pre-compressional parameters. The prepared gas powered tablets are evaluated to post-compressional analysis of parameter such as hardness, friability, weight variation , thickness, drug content, lag time subsequently buoyancy time and in-vitro dissolution studies and swelling index. All the pre and post-compressional parameter are evaluated the results were within acceptable limits. The results of in-vitro buoyancy time and lag time study, the values of in-vitro buoyancy time ranges from 38 to 960 min where as floating lag time ranges from 3.5 to 60 min. The formulation F4 shows the lag time 3.5 min and buoyancy time 960 min. The results of in-vitro buoyancy time and lag time study revealed that as the concentration of sodium bicarbonate increases there is increase in total buoyancy time and decrease in lag time. It is evident from the in-vitro dissolution data that increase in citric acid concentration increased the release rate but reduced the floating time, probably due to of excess carbon dioxide, disturbing the monolithic tablet. The citric acid level in the formulations greatly influenced the drug release. The formulation, F-4 shows maximum drug release at the end of 12 hrs. Form this study, it is concluded that, the formulation retained for longer periods of time in the stomach and provides controlled release of the drug. Hence it

  17. In vitro release studies of piroxicam from oil-in-water creams and hydroalcoholic gel topical formulations.

    Science.gov (United States)

    Rafiee-Tehrani, M; Mehramizi, A

    2000-04-01

    The importance of piroxicam, a therapeutic anti-inflammatory drug, is well known. Because of gastrointestinal disorders, dermatological dosage forms are recommended most. In our first studies, oil-in-water (O/W) creams of piroxicam (1% concentration) were prepared using glyceryl monostearate (GMS), stearic acid, and triethanolamine as additive ingredients. In our second studies, hydroalcoholic transparent gel formulations of this drug in a 0.5% concentration were prepared using hydroxypropylcellulose (HPC) as the gelling agent. The release of piroxicam from all formulations via dialysis through a cellulose membrane into phosphate buffer pH 6.8 at 37 degrees C was studied. The effects of additives such as propylene glycol and 2-propanol on the drug release were also investigated. The release profiles from the standpoint of diffusion-controlled processes, as well as zero-order and first-order kinetics, were evaluated, and relevant parameters, such as diffusion coefficient, permeability coefficient, and partition coefficient, were calculated. The release obeys both the diffusion mechanism and first-order kinetics. The drug release from gel formulations containing 10%, 20%, and 30% propylene glycol was decreased due to the enhancement of viscosity. However, the limpidity of these formulations was improved. Moreover, the release of drug from gel formulations containing 15% and 20% of 2-propanol was increased. These results show that a hydroalcoholic gel formulation with HPC is a more suitable preparation of piroxicam when compared with an O/W cream formulation.

  18. Control of Aedes albopictus larvae using time-release larvicide formulations in Louisiana.

    Science.gov (United States)

    Nasci, R S; Wright, G B; Willis, F S

    1994-03-01

    The ability of time-release formulations of larvicides and insect growth regulators (IGRs) to provide long-term control of Aedes albopictus was investigated in the field. Larvicides used in the study were Bactimos pellets (Bacillus thuringiensis var. israelensis, active ingredient) and Abate pellets (temephos, active ingredient). The IGR Altosid (methoprene, active ingredient) was used in pellet and sand formulations. Application rates were higher than label recommendations. In a preliminary test, clay flower bowls were treated with 2 g of material. Bactimos pellets failed to provide control after 60 days. Abate pellets and the Altosid formulations provided essentially 100% control for 150 days. After 360 days in the field, the Abate pellets produced 100% larval mortality, and significant levels of control were provided by the Altosid formulations and the Bactimos pellets. In a small-scale operational trial of this technique, 1 g of Altosid pellets was applied to every container that could be located in 2 urban residential neighborhoods in Lake Charles, LA. Aedes albopictus biting populations were monitored weekly in the treated areas and in an untreated control area. Biting population densities declined significantly in treated areas compared with the control area. Results suggested that long-term control of Ae. albopictus populations can be achieved economically with one application of Altosid pellets or Abate pellets in containers.

  19. Formulation and Mathematical Optimization of Controlled Release Calcium Alginate Micro Pellets of Frusemide

    Directory of Open Access Journals (Sweden)

    Amitava Ghosh

    2013-01-01

    Full Text Available Objective. Frusemide loaded calcium alginate micropellets, an oral microparticulate delivery system, was statistically optimized exhibiting prolonged therapeutic action minimizing its adverse effects. Methods. Ionotropic Gelation technique was adopted employing 32 Factorial designs and keeping the entire process free from organic solvents. Physicochemical and the release characteristics of the prepared formulations were studied, keeping variations only in sodium alginate (primary polymer and Acrycoat E30D (copolymer dispersion. Result. Sodium alginate was predominant over Acrycoat E30D in all batches. Nonadditives or interaction was observed to be insignificant. Multiple regressions produced second-order polynomial equation, and the predictive results obtained were validated with high degree of correlation. The in vivo study applauded that optimized calcium alginate micropellets of frusemide can produce a much greater diuretic effect over an extended period of 24 hours. Conclusion. This study reveals that the potential of a single dose of the mathematically optimized micro pellets of frusemide formulation is sufficient in the management of peripheral edema and ascites in congestive heart failure and as well in the treatment of chronic hypertension, leading to better patient compliance, and can be produced with minimum experimentation and time, proving far more cost-effective formulation than the conventional methods of formulating dosage forms.

  20. Evaluation of Pharmaceutical Quality of Mesalamine Delayed Release Tablets Using a New High Sensitivity Reversed-Phase UPLC Method for its Genotoxic/Aniline Impurity

    Directory of Open Access Journals (Sweden)

    Rakshit Kanubhai Trivedi

    2011-01-01

    Full Text Available A reversed phase ultra performance liquid chromatography (UPLC method was developed and validated for the quantification of aniline in mesalamine delayed-release tablets. The optimization of the experimental condition was carried out considering some important requirements like, detection limit, short run time and reproducibility. In the present study, isocratic reversed-phase UPLC method was developed for determination and separation of aniline from the drug product. The drug and impurity are well separated by using a reversed phase (Reprosil Gold C18-XBD column and mobile phase comprising of buffer pH 6.0 and acetonitrile in the ratio of 90:10 v/v. Other UPLC parameters which were optimised are flow rate, 0.5 mL/min; detection wavelength, 200 nm; column oven temperature, 50 °C and injection volume 7 µL. Stability indicating capability was also established by forced degradation experiments. The method was validated as per ICH guideline. LOQ (limit of quantification concentration (18 ng/mL was found precise with RSD of less than 2%. In essence, the present study provides an improved low detection limit and lower run time for evaluation of pharmaceutical quality of mesalamine delayed-release formulation. Moreover, the developed method was also successfully applied for quantification of aniline in mesalamine delayed-release formulation. The same method can also be used for determination of aniline from drug substances.

  1. 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.

  2. Quil A-lipid powder formulations releasing ISCOMs and related colloidal structures upon hydration.

    Science.gov (United States)

    Demana, Patrick H; Davies, Nigel M; Hook, Sarah; Rades, Thomas

    2005-03-02

    The aim of the present study was to prepare solid Quil A-cholesterol-phospholipid formulations (as powder mixtures or compressed to pellets) by physical mixing or by freeze-drying of aqueous dispersions of these components in ratios that allow spontaneous formation of ISCOMs and other colloidal structures upon hydration. The effect of addition of excess cholesterol to the lipid mixtures on the release of a model antigen (PE-FITC-OVA) from the pellets was also investigated. Physical properties were evaluated by X-ray powder diffractometry (XPRD), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), and polarized light microscopy (PLM). Characterization of aqueous colloidal dispersions was performed by negative staining transmission electron microscopy (TEM). Physically mixed powders (with or without PE-FITC-OVA) and pellets prepared from the same powders did not spontaneously form ISCOM matrices and related colloidal structures such as worm-like micelles, ring-like micelles, lipidic/layered structures and lamellae (hexagonal array of ring-like micelles) upon hydration as expected from the pseudo-ternary diagram for aqueous mixtures of Quil A, cholesterol and phospholipid. In contrast, spontaneous formation of the expected colloids was demonstrated for the freeze-dried lipid mixtures. Pellets prepared by compression of freeze-dried powders released PE-FITC-OVA slower than those prepared from physically mixed powders. TEM investigations revealed that the antigen was released in the form of colloidal particles (ISCOMs) from pellets prepared by compression of freeze-dried powders. The addition of excess cholesterol slowed down the release of antigen. The findings obtained in this study are important for the formulation of solid Quil A-containing lipid articles as controlled particulate adjuvant containing antigen delivery systems.

  3. Phosphate-clay mixture as adsorbent and slow released formulation for carbofuran

    Science.gov (United States)

    Dahchour, Abdelmalek; El Hadki, Ahmed; Zrineh, Abdellah; El Hajjaji, Souad

    2017-04-01

    Improvement of agricultural production relies on the use of phosphates as soil amendment. The presence of phosphates in soil could interact with other components of the soil and lead to various interactions with intrants such as pesticides and other fertilizers. Such interactions could play positive role as adsorbents and subsequently as controlled released formulations for pollutants in general and pesticide particularly. In this work, we have aimed to study interactions of different combinations (in %) of clay bentonite (B) and natural phosphate (NP). Tested ratios of B/NP were 25/75, 50/50 and 75/25. The degree of retention was evaluated in batch equilibrium system using 20 ppm aqueous solutions of carbofuran (CF) and B/NP at different ratios. Results showed that the maximum adsorption of CF was achieved within 8 hours after starting the experiment. Best result was obtained with the ratio of B/NP (50/50) resulting 30% of carbofuran adsorbed. Desorption study showed that CF was readily released from this material at smaller amounts not exceeding 17% of the retained pesticide. This could be considered as a positive achievement in terms of released formulation. Actually, carbofuran has high solubility in water and is subject to potential movement in the soil. This could lead to contamination of groundwater. Its slow release would make it available to the target in the soil and prevent its movement downward and far from the point of application. Adaptation of adsorption and desorption data to Freundlich and Langmuir model showed that the best fit was obtained with Frrendlich model.

  4. A pharmacokinetic comparison of the modified release capsule and a plain tablet formulation of mebeverine.

    Science.gov (United States)

    Winsemius, A; Meuwsen, I M; Boon, C; van der Laan, A; Brekle, A; de Vries, M

    2002-11-01

    This study was conducted to compare the pharmacokinetic properties of the modified release 200 mg capsule of mebeverine and the plain 135 mg tablet of mebeverine after single and multiple doses in 12 healthy subjects in a randomised, crossover design. Single doses were given on days 1 and 7 and multiple doses (200 mg b.i.d. for the capsule and 135 mg t.i.d. for the tablet) on days 2-6 of the study. The 200 mg modified release capsule of mebeverine has extended release properties, as indicated by a lower Cmax, a later tmax and a longer elimination half-life than the plain tablet, while the bioavailability is optimal. No significant accumulation occurs after multiple doses of either formulation. The twice-daily dosage regimen of the 200 mg modified release capsule is a good alternative to the three times daily dosage regimen of the 135 mg plain tablet, because the reduced daily intake is likely to benefit patient compliance.

  5. Transient early neurotrophin release and delayed inflammatory cytokine release by microglia in response to PAR-2 stimulation.

    Science.gov (United States)

    Chen, Chen-Wen; Chen, Qian-Bo; Ouyang, Qing; Sun, Ji-Hu; Liu, Fang-Ting; Song, Dian-Wen; Yuan, Hong-Bin

    2012-06-25

    Activated microglia exerts both beneficial and deleterious effects on neurons, but the signaling mechanism controlling these distinct responses remain unclear. We demonstrated that treatment of microglial cultures with the PAR-2 agonist, 2-Furoyl-LIGRLO-NH2, evoked early transient release of BDNF, while sustained PAR-2 stimulation evoked the delayed release of inflammatory cytokines (IL-1 β and TNF-α) and nitric oxide. Culture medium harvested during the early phase (at 1 h) of microglial activation induced by 2-Furoyl-LIGRLO-NH2 (microglial conditioned medium, MCM) had no deleterious effects on cultured neurons, while MCM harvested during the late phase (at 72 h) promoted DNA fragmentation and apoptosis as indicated by TUNEL and annexin/PI staining. Blockade of PAR-1 during the early phase of PAR-2 stimulation enhanced BDNF release (by 11%, small but significant) while a PAR-1 agonist added during the late phase (24 h after 2-Furoyl-LIGRLO-NH2 addition) suppressed the release of cytokines and NO. The neuroprotective and neurotoxic effects of activated microglial exhibit distinct temporal profiles that are regulated by PAR-1 and PAR-2 stimulation. It may be possible to facilitate neuronal recovery and repair by appropriately timed stimulation and inhibition of microglial PAR-1 and PAR-2 receptors.

  6. Evaluation of Prosopis africana Seed Gum as an Extended Release Polymer for Tablet Formulation.

    Science.gov (United States)

    Nadaf, Sameer; Nnamani, Petra; Jadhav, Namdeo

    2015-06-01

    In the present work, an attempt has been made to screen Prosopis africana seed gum (PG), anionic polymer for extended release tablet formulation. Different categories of drugs (charge basis) like diclofenac sodium (DS), chlorpheniramine maleate (CPM), and ibuprofen (IB) were compacted with PG and compared with different polymers (charge basis) like xanthan gum (XG), hydroxypropyl methyl cellulose (HPMC-K100M), and chitosan (CP). For each drug, 12 batches of tablets were prepared by wet granulation technique, and granules were evaluated for flow properties, compressibility, and compactibility by Heckel and Leuenberger analysis, swelling index, in vitro dissolution studies, etc. It has been observed that granules of all batches showed acceptable flowability. According to Heckel and Leuenberger analysis, granules of PG-containing compacts showed similar and satisfactory compressibility and compactibility compared to granules of other polymers. PG showed significant swelling (P < 0.05) compared to HPMC, and better than CP and XG. Differential scanning calorimetry (DSC), X-ray diffraction (XRD), and Fourier transform infrared (FTIR) study showed no interaction between drugs and polymers. From all PG-containing compacts of aforesaid drugs, drug release was sustained for 12 h following anomalous transport. Especially, polyelectrolyte complex formation retarded the release of oppositely charged drug (CPM-PG). However, extended release was noted in both anionic (DS) and nonionic (IB) drugs, maybe due to swollen gel. All compacts were found to be stable for 3-month period during stability study. This concludes that swelling and release retardation of PG has close resemblance to HPMC, so it can be used as extended release polymer for all types of drugs.

  7. Analyzing the impact of different excipients on drug release behavior in hot-melt extrusion formulations using FTIR spectroscopic imaging.

    Science.gov (United States)

    Pudlas, Marieke; Kyeremateng, Samuel O; Williams, Leonardo A M; Kimber, James A; van Lishaut, Holger; Kazarian, Sergei G; Woehrle, Gerd H

    2015-01-25

    The drug release performance of hot-melt extrudate formulations is mainly affected by its composition and interactions between excipients, drug and the dissolution media. For targeted formulation development, it is crucial to understand the role of these interactions on the drug release performance of extrudate formulations. Attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopic imaging was used with an in-situ flow-cell device to analyze the impact of different excipients on drug release from extrudates. The compositions differed in the type of polymer (copovidone and Soluplus®), the salt or acid form of ibuprofen and the addition of sodium carbonate. For comparison, conventional USP (United States Pharmacopeia) Apparatus 2 dissolution studies were performed. FTIR imaging revealed that differences in the drug release rate were mainly due to drug-polymer interactions. Ibuprofen acid showed interactions with the matrix polymer and exhibited a slower drug release compared to non-interacting ibuprofen salt. Addition of sodium carbonate to the ibuprofen acid containing formulations enhanced the drug release rate of these systems by interfering with the drug-polymer interactions. In addition, drug release rates also depended on the polymer type, showing faster drug release rates for extrudate formulations containing copovidone compared to Soluplus®. FTIR imaging revealed that the stronger the drug-polymer interaction in the formulations, the slower the drug release. The addition of sodium carbonate improved release as it reduces drug-polymer interactions and allows for the formation of the more water-soluble ibuprofen salt.

  8. The Multimedia Environmental Pollutant Assessment System (MEPAS){reg_sign}: Source-term release formulations

    Energy Technology Data Exchange (ETDEWEB)

    Streile, G.P.; Shields, K.D.; Stroh, J.L.; Bagaasen, L.M.; Whelan, G.; McDonald, J.P.; Droppo, J.G.; Buck, J.W.

    1996-11-01

    This report is one of a series of reports that document the mathematical models in the Multimedia Environmental Pollutant Assessment System (MEPAS). Developed by Pacific Northwest National Laboratory for the US Department of Energy, MEPAS is an integrated impact assessment software implementation of physics-based fate and transport models in air, soil, and water media. Outputs are estimates of exposures and health risk assessments for radioactive and hazardous pollutants. Each of the MEPAS formulation documents covers a major MEPAS component such as source-term, atmospheric, vadose zone/groundwater, surface water, and health exposure/health impact assessment. Other MEPAS documentation reports cover the sensitivity/uncertainty formulations and the database parameter constituent property estimation methods. The pollutant source-term release component is documented in this report. MEPAS simulates the release of contaminants from a source, transport through the air, groundwater, surface water, or overland pathways, and transfer through food chains and exposure pathways to the exposed individual or population. For human health impacts, risks are computed for carcinogens and hazard quotients for noncarcinogens. MEPAS is implemented on a desktop computer with a user-friendly interface that allows the user to define the problem, input the required data, and execute the appropriate models for both deterministic and probabilistic analyses.

  9. 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

  10. Comparison of drug release from poly(lactide-co-glycolide) microspheres and novel fibre formulations.

    Science.gov (United States)

    Campbell, Christopher S J; Delgado-Charro, M Begoña; Camus, Olivier; Perera, Semali

    2016-03-01

    Intraperitoneal cisplatin delivery has recently been shown to benefit ovarian cancer patients. Cisplatin-containing poly(lactide-co-glycolide) (PLGA) microspheres have been proposed for cisplatin delivery. The drug loading of cisplatin containing microspheres produced elsewhere is 3-10%w. Similar microspheres are reported here with a mean diameter of 38.8 µm, and a drug loading of 11.7%w, but using ethyl acetate as a safer solvent. In addition, novel formulations of cisplatin-containing solid and hollow PLGA 65:35 (lactide:glycolide) fibres were prepared and are reported here for the first time. PLGA hollow fibres were produced by phase inversion with a high drug loading of 27%w. Mechanistic mathematical models were applied to the cisplatin release profiles to allow quantitative comparison of microsphere, solid fibre and hollow fibre formulations. The diffusion coefficient of cisplatin eluting from a typical batch of PLGA microspheres was 4.8 × 10(-13) cm(2) s(-1); this low diffusivity of cisplatin in microspheres was caused by the low porosity of the polymer matrix. The diffusion coefficients of cisplatin eluting from a batch of PLGA solid fibres and hollow fibres were 6.1 × 10(-10) and 3.3 × 10(-10) cm(2) s(-1), respectively. These fibres allowed the controlled release of high doses of cisplatin over four days and may represent an improvement in slow release technology for treatment of ovarian cancer.

  11. 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.

  12. In vitro drug release and percutaneous behavior of poloxamer-based hydrogel formulation containing traditional Chinese medicine.

    Science.gov (United States)

    Wang, Wenyi; Hui, Patrick C L; Wat, Elaine; Ng, Frency S F; Kan, Chi-Wai; Wang, Xiaowen; Wong, Eric C W; Hu, Huawen; Chan, Ben; Lau, Clara B S; Leung, Ping-Chung

    2016-12-01

    For the treatment of atopic dermatitis (AD), we have developed a transdermal functionalized textile therapy based on thermosensitive poloxamer 407 (P407) hydrogel containing a traditional Chinese herbal medicine. This study aims to investigate the effects of various formulation variables of P407/carboxymethyl cellulose sodium (P407/CMCs) composite hydrogel on the release of Cortex Moutan (CM) extract. Concentrations of P407 and CMCs showed significant influence on the release due to alteration of bulk viscosity of the system. An increase in pH values of release medium was found to appreciably impede the release of polar drug (CM) due to ionization. Elevated temperatures were also shown to facilitate the drug release. Moreover, the diffusional release behavior of CM from P407/CMCs composite hydrogel was found to follow the first-order kinetic model. Additionally, transdermal studies showed that permeability of the drug through the skin can be enhanced with addition of CMCs in the hydrogel formulation.

  13. Application of percolation theory in the study of an extended release Verapamil hydrochloride formulation.

    Science.gov (United States)

    Gonçalves-Araújo, Tamara; Rajabi-Siahboomi, Ali R; Caraballo, Isidoro

    2008-09-01

    The percolation theory studies the critical points or percolation thresholds of the system, where one component of the system undergoes a geometrical phase transition, starting to connect the whole system. The objective of the present paper was to study the existence of critical points governing the water and drug transport inside hydroxypropylmethylcellulose (HPMC) hydrophilic matrix systems obtained with different polymer viscosity grades. For this purpose, extended release formulations of Verapamil HCl, have been prepared and studied. The percolation theory has been applied for the first time to multi-component hydrophilic matrices. The materials used to prepare the tablets were Verapamil HCl, four different viscosity grades of HPMC, microcrystalline cellulose, lactose, magnesium stearate and colloidal silicon dioxide NF. In order to estimate the percolation threshold, the behaviour of the kinetic parameters with respect to the volumetric fraction of each component at time zero, was studied. From the point of view of the percolation theory, the optimum concentration for all the studied polymers, to obtain a hydrophilic matrix system for the controlled release of Verapamil HCl is higher than 20% (v/v) HPMC. Above 20% (v/v) HPMC, an infinite cluster of excipient would be formed, ensuring uniform hydration, maintaining integrity of the system and controlling the drug release.

  14. Formulation and evaluation of Zidovudine loaded chitosan Microspheres for controlled release

    Directory of Open Access Journals (Sweden)

    Kesari Asha

    2012-03-01

    Full Text Available The aim of this study was to formulate and evaluate zidovudine loaded chitosan microspheres for controlled drug release. Microspheres were prepared by emulsification method using gluteraldehyde as crosslinking agent. The prepared microspheres were characterized for their yield and drug loading, as well by Fourier transform infrared spectroscopy (FTIR, X-ray powder diffractometry and Scanning electron microscopy. The in vitro release studies were performed in pH 7.4, phosphate buffer. The prepared microspheres were free flowing and spherical in shape. The drugloaded microspheres showed 72-94% of entrapment and release was extended up to 12h. The infrared spectra showed stable character of zidovudine in the drugloaded microspheres and revealed the absence of drugpolymer interactions. X-ray diffraction patterns showed that there was decrease in crystallinity of the drug. Scanning electron microscopy study revealed that the microspheres were spherical and porous in nature. It was found that the drug: polymer ratio, the stirring speed, the concentration of surfactant, and the amount of gluteraldehyde used for crosslinking were the most significant variables which influenced the size of the chitosan microspheres under the applied experimental condition.

  15. Influence of Drug Properties and Formulation on In Vitro Drug Release and Biowaiver Regulation of Oral Extended Release Dosage Forms.

    Science.gov (United States)

    Lin, Zhongqiang; Zhou, Deliang; Hoag, Stephen; Qiu, Yihong

    2016-03-01

    Bioequivalence (BE) studies are often required to ensure therapeutic equivalence for major product and manufacturing changes. Waiver of a BE study (biowaiver) is highly desired for such changes. Current regulatory guidelines allow for biowaiver of proportionally similar lower strengths of an extended release (ER) product provided it exhibits similar dissolution to the higher strength in multimedia. The objective of this study is to demonstrate that (1) proportionally similar strengths of ER tablets exhibiting similar in vitro dissolution profiles do not always assure BE and (2) different strengths that do not meet the criteria for dissolution profile similarity may still be bioequivalent. Four marketed ER tablets were used as model drug products. Higher and lower (half) strength tablets were prepared or obtained from commercial source. In vitro drug release was compared using multi-pH media (pH 1.2, 4.5, 6.8) per regulatory guidance. In vivo performance was assessed based on the available in vivo BE data or established in vitro-in vivo relationships. This study demonstrated that the relationship between in vitro dissolution and in vivo performance is complex and dependent on the characteristics of specific drug molecules, product design, and in vitro test conditions. As a result, proportionally similar strengths of ER dosage forms that meet biowaiver requirements per current regulatory guidelines cannot ensure bioequivalence in all cases. Thus, without an established relationship between in vitro and in vivo performance, granting biowaiver based on passing in vitro tests may result in the approval of certain bioinequivalent products, presenting risks to patients. To justify any biowaiver using in vitro test, it is essential to understand the effects of drug properties, formulation design, product characteristics, test method, and its in vivo relevance. Therefore, biowaiver requirements of different strengths of ER dosage forms specified in the current regulatory

  16. Blends of hydrophobic and swelling agents in the swelling layer in the preparation of delayed-release pellets of a hydrophilic drug with low MW: Physicochemical characterizations and in-vivo evaluations

    Directory of Open Access Journals (Sweden)

    Chang You

    2014-08-01

    Full Text Available In this study, a hydrophobic material, ethylcellulose, which was used as its aqueous suspension Surelease®, was combined with a swelling agent as the swelling layer to prepare delayed-release pellets for Danshensu, which is a hydrophilic drug with low MW. A rupturable, delayed-release pellet consists of a drug core, a swelling layer containing a swelling agent (cross-linked sodium carboxymethyl cellulose with a hydrophobic agent (Surelease®, and a controlled layer composed by an insoluble, water-permeable polymeric coating (aqueous ethylcellulose dispersions was developed in a fluidised bed. Results showed that blending Surelease® into the swelling layer could effectively extend the release of Danshensu from the pellets, which may be attributed to the slowed swelling rate by reduction of water penetration and improvement of mechanical integrity of the swelling layer. Drug in the delayed pellets showed sustained release in beagle dogs after oral administration with comparable in-vivo exposure to the uncoated drug pellets. In conclusion, blends of hydrophobic and swelling agents in the swelling layer in double-membrane pellets could achieve a delayed drug-release profile in vitro, as well as delayed and sustained absorption in vivo for highly soluble, low-MW drug. The present study highlighted the potential use of a delayed-release system for other hydrophilic, low-MW drugs to meet the formulation requirements for chronopharmacological diseases.

  17. STUDYING THE IMPACT OF FORMULATION AND PROCESSING PARAMETERS ON THE RELEASE CHARACTERISTICS FROM HYDROXYPROPYL METHYLCELLULOSE MATRIX TABLETS OF DICLOFENAC.

    Science.gov (United States)

    Elzayat, Ehab M; Abdel-Rahman, Ali A; Ahmed, Sayed M; Alanazi, Fars K; Habib, Walid A; Sakr, Adel

    2016-01-01

    Hydrophilic matrices, especially HPMC based, are widely used to provide sustained delivery where drug release occurs mainly by diffusion. A 3(2) full factorial design was used to develop and evaluate HPMC matrix tablet for sustained delivery of diclofenac. The influences of polymer concentration/viscosity, diluent type/ratio, drug load/solubility, compression force and pH change on drug release were investigated. Ten tablet formulations were prepared using wet granulation. HPMC K15M (10-30% w/w) was used as the polymer forming matrix. The release kinetics, compatibility studies, lot reproducibility and effect on storage were discussed. Increasing polymer concentration and compression force showed antagonistic effect on release rate. Mannitol tends to increase release rate more than lactose. Reversing diluent ratio between lactose and MCC did not affect drug release. Changing pH resulted in burst release whereas drug solubility is pH independent. F1 showed similar release to Voltaren SR and followed Higuchi model. Drug and polymer were compatible to each other. The formulation is stable at long and intermediate conditions with a significant increase in release rate at accelerated conditions due to water uptake and polymer swelling. The developed formulation was successful for a sustained delivery of diclofenac.

  18. Residue and bio-efficacy evaluation of controlled release formulations of imidacloprid against pests in soybean (Glycine max).

    Science.gov (United States)

    Adak, Totan; Kumar, Jitendra; Dey, Debjani; Shakil, N A; Walia, S

    2012-01-01

    Controlled release (CR) formulations of imidacloprid (1-(6 chloro-3-pyridinyl methyl)-N- nitro imidazolidin-2- ylideneamine) were prepared using novel amphiphilic polymers synthesized from polyethylene glycol and aliphatic diacids employing encapsulation technique. The bioefficacy of the prepared CR formulations was evaluated against major pests of soybean, namely stem fly, Melanagromyza sojae Zehntmer and white fly, Bemisia tabaci Gennadius along with a commercial formulation at the experimental farm of Indian Agricultural Research Institute (IARI), New Delhi during kharif 2009 and 2010. Most of the CR formulations of imidacloprid gave significantly better control of the pests compare to its commercial formulations, however the CR formulations, Poly [poly (oxyethylene-1000)-oxy suberoyl] amphiphilic polymer based formulation performed better over others for controlling of both stem fly incidence and Yellow Mosaic Virus (YMV) infestation transmitted by white fly. Some of the developed CR formulations recorded higher yield over commercial formulation and control. Nodulation pattern of soybean was not affected due to treatment of CR and commercial formulations of imidacloprid. Also the residues of imidacloprid in seed and soil at harvest were not detectable for both CR and commercial formulations.

  19. 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

  20. Formulation and development of release modulated colon targeted system of meloxicam for potential application in the prophylaxis of colorectal cancer.

    Science.gov (United States)

    Patel, Mayur M; Amin, Avani F

    2011-05-01

    The objective of the present study was to develop a colon targeted system of meloxicam for potential application in the prophylaxis of colorectal cancer. Efficacy of selective cyclooxygenase-2 inhibitors has been proven in colorectal cancer. Meloxicam is a selective cyclooxygenase-2 inhibitor with pH-dependent solubility. To achieve pH-independent drug release of meloxicam, pH modifying agents (buffering agents) were used. Meloxicam tablets containing polyethylene oxide were dually coated with ethyl cellulose containing hydrophilic material, polyethylene glycol as an inner coating layer and methyl acrylate, methyl methacrylate, and methacrylic acid copolymer (Eudragit® FS 30D) as outer coating layer for colon targeting. Optimized tablet formulations demonstrated good potential to deliver the drug to the colon by successfully exhibiting a lag time of 5 h during in vitro drug release study. An in vivo evaluation study conducted to ascertain pharmacokinetic parameters in rabbits revealed that the onset of drug absorption from the coated tablets (T(lag time) = 4.67 ± 0.58 h) was significantly delayed compared to that from the uncoated tablets. The AUC(0→)(t) and AUC(0→∞) for coated tablets were lower than of uncoated tablets, although the difference was not significant (p > 0.01). The roentgenography study revealed that the tablet remained intact, until it reached the colon (5 h), which demonstrates that the system can efficiently deliver the drug to the colon. This study demonstrated that a meloxicam-loaded colon targeted system exhibited promising targeting and hence may be used for prophylaxis of colorectal cancer.

  1. Design and development of ankle-foot prosthesis with delayed release of plantarflexion

    Directory of Open Access Journals (Sweden)

    Michael Mitchell, MSc

    2013-05-01

    Full Text Available A computer-controlled mechanism that fits a standard ankle-foot prosthesis was designed to capture the absorbed energy in the ankle and delay its release until specific times in the gait cycle. This mechanism used a direct current motor to take up and hold the compression of a carbon-fiber ankle joint. Based on the timing of the contact forces between the foot and the ground, a microprocessor released the spring at preset times later in the gait cycle. This mechanism was added to a Talux prosthetic foot and was employed by a user of a conventional energy-storage ankle-foot prosthesis. His gait was recorded using a motion analysis system. Five settings: 0, 55, 65, 75, and 85 ms delay were tested on separate days, and the standard kinematic and kinetic gait data were recorded. The user reported some settings were more comfortable than others. When these preferences were tested with a randomized double-blind trial, the preferences were not consistent. A second user showed a preference for the 55 ms delay. The modifications to the device resulted in changes to the gait of the subjects, including increased cadence and kinematics of the unaffected joints and a longer, slower push from the ankle, which was noticed by both of the subjects.

  2. Design and development of ankle-foot prosthesis with delayed release of plantarflexion.

    Science.gov (United States)

    Mitchell, Michael; Craig, Katelynn; Kyberd, Peter; Biden, Edmund; Bush, Greg

    2013-01-01

    A computer-controlled mechanism that fits a standard ankle-foot prosthesis was designed to capture the absorbed energy in the ankle and delay its release until specific times in the gait cycle. This mechanism used a direct current motor to take up and hold the compression of a carbon-fiber ankle joint. Based on the timing of the contact forces between the foot and the ground, a microprocessor released the spring at preset times later in the gait cycle. This mechanism was added to a Talux prosthetic foot and was employed by a user of a conventional energy-storage ankle-foot prosthesis. His gait was recorded using a motion analysis system. Five settings: 0, 55, 65, 75, and 85 ms delay were tested on separate days, and the standard kinematic and kinetic gait data were recorded. The user reported some settings were more comfortable than others. When these preferences were tested with a randomized double-blind trial, the preferences were not consistent. A second user showed a preference for the 55 ms delay. The modifications to the device resulted in changes to the gait of the subjects, including increased cadence and kinematics of the unaffected joints and a longer, slower push from the ankle, which was noticed by both of the subjects.

  3. Factors affecting the design of slow release formulations of herbicides based on clay-surfactant systems. A methodological approach.

    Directory of Open Access Journals (Sweden)

    María Del Carmen Galán-Jiménez

    Full Text Available A search for clay-surfactant based formulations with high percentage of the active ingredient, which can yield slow release of active molecules is described. The active ingredients were the herbicides metribuzin (MZ, mesotrione (MS and flurtamone (FL, whose solubilities were examined in the presence of four commercial surfactants; (i neutral: two berols (B048, B266 and an alkylpolyglucoside (AG6202; (ii cationic: an ethoxylated amine (ET/15. Significant percent of active ingredient (a.i. in the clay/surfactant/herbicide formulations could be achieved only when most of the surfactant was added as micelles. MZ and FL were well solubilized by berols, whereas MS by ET/15. Sorption of surfactants on the clay mineral sepiolite occurred mostly by sorption of micelles, and the loadings exceeded the CEC. Higher loadings were determined for B266 and ET/15. The sorption of surfactants was modeled by using the Langmuir-Scatchard equation which permitted the determination of binding coefficients that could be used for further predictions of the sorbed amounts of surfactants under a wide range of clay/surfactant ratios. A possibility was tested of designing clay-surfactant based formulations of certain herbicides by assuming the same ratio between herbicides and surfactants in the formulations as for herbicides incorporated in micelles in solution. Calculations indicated that satisfactory FL formulations could not be synthesized. The experimental fractions of herbicides in the formulations were in agreement with the predicted ones for MS and MZ. The validity of this approach was confirmed in in vitro release tests that showed a slowing down of the release of a.i. from the designed formulations relative to the technical products. Soil dissipation studies with MS formulations also showed improved bioactivity of the clay-surfactant formulation relative to the commercial one. This methodological approach can be extended to other clay-surfactant systems for

  4. 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.

  5. An assessment of the clinical equivalence of valproate chrono and extended release divalproex formulations

    Directory of Open Access Journals (Sweden)

    Rajesh B

    2007-01-01

    Full Text Available Objective: No guideline currently exists to choose the clinically equivalent dose of divalproex extended release (ER formulation while switching over from valproate chrono formulation. To address this issue, we evaluated the serum valproate concentration following switch over from valproate chrono to divalproex ER in persons with epilepsy. Materials and Methods: An open label study was conducted in two parts, each for a period of two months. During Part I, patients on regular twice-daily dose of valproate chrono were switched over to once daily divalproex ER (DESVAL ER ® based on the dose escalation recommended when switching over from divalproex DR to ER formulation as the guideline. During Part II, we switched from valproate chrono to divalproex ER with same dosage. Serum valproate concentration, seizure frequency and side effects were assessed serially for two months after changeover and compared with the preswitch data. Results: During Part I, compared to the baseline level, there was a significant increase in mean serum valproate level at two months (67.0 ± 28.4 mg/ml versus 91.9 ± 3.5 mg/ml, P 0.004. With the same dose conversion during Part II, the mean valproate level did not significantly differ before and after the switch (81.5 mg/dl versus 85.7 mg/dl, P 0.08. The mean monthly seizure frequencies and serum ammonia levels did not change during either part. No significant adverse effects occurred. Conclusion: The results of this open label study with small number of patients need to be replicated among larger patient sample through a randomized control design before recommending same dose conversion from valproate chrono to divalproex ER without change in efficacy and tolerability,

  6. Ketorolac trometamol topical formulations: release behaviour, physical characterization, skin permeation, efficacy and gastric safety.

    Science.gov (United States)

    El-Setouhy, Doaa Ahmed; El-Ashmony, Sahar Mohy Ahmed

    2010-01-01

    The objective of this study was to improve systemic delivery of the highly analgesic ketorolac trometamol (ketorolac tromethamine) via the transdermal route, through cost-effective topical formulations, to avoid most of the problems associated with ketorolac trometamol therapy. In-vitro release behaviour of the drug from different microemulsion and emulgel formulations was evaluated. E2 emulgel (based on isopropyl myristate as penetration enhancer) and E7 emulgel (based on Brij 92 as penetration enhancer) were evaluated for their physical properties, rat skin permeation, in-vivo analgesic effect (hot-plate test and the paw pressure test), acute and chronic anti-inflammatory activity and gastric safety. Isopropyl myristate and the synergistic effect of the two known penetration enhancers (propylene glycol and Brij 92) significantly modulated drug permeation and may be a promising approach for the transdermal delivery of ketorolac trometamol and other drugs. Selected in-vivo tested formulae (E2 and E7) caused significantly less ulcer score and less gastric erosion compared with oral ketorolac trometamol. E7 showed significantly higher analgesic and anti-inflammatory activity compared with E2 with no significant difference compared with oral ketorolac trometamol. The developed ketorolac trometamol E7 emulgel appeared promising for dermal and transdermal delivery of ketorolac trometamol, which would circumvent most of the problems associated with drug therapy.

  7. An in vitro-in vivo correlation study of modified release formulations of Venlafaxine.HCl

    Directory of Open Access Journals (Sweden)

    Aravindaraj, J.R.

    2014-09-01

    Full Text Available A single dose, randomized, complete and four treatment cross over study was conducted in healthy human subjects for IVIVC of venlafaxine.HCl, Plasma concentrations were estimated by a simple, rapid, sensitive and validated LCMS method, Cetirizine was used as the internal standard (IS, The analytes and the IS were extracted from the human plasma by liquid–liquid extraction technique, The reconstituted samples were chromatographed on Kromasil C18 column using an isocratic solvent mixture [acetonitrile–water, 90:10 (v/v] at a flow rate of 0.5 mL/min, Method validation was performed as per FDA guidelines and the results met the acceptance criteria, USP dissolution apparatus I (Basket and pH 6.8 at 100 rpm was found to yield acceptable IVIVC for the drug, The developed dissolution method would discriminate bioinequivalent batches, A ‘Level A’ correlation was observed for the selected formulations at the in vitro dissolution conditions developed, The dissolution method predicted the best absorption rate for the selected modified release formulations, The validity of the correlation was assessed by determining how well the IVIVC model could predict the rate and the extent of absorption as characterized by Cmax and AUC, A percent prediction error of = 10 % for C max and AUC obtained establishes the predictability of the developed IVIVC model, It may, therefore, be concluded that the developed dissolution method can surrogate for human bioequivalence study.

  8. Effects of formulation variables and characterization of guaifenesin wax microspheres for controlled release.

    Science.gov (United States)

    Mani, Narasimhan; Park, M O; Jun, H W

    2005-01-01

    Sustained-release wax microspheres of guaifenesin, a highly water-soluble drug, were prepared by the hydrophobic congealable disperse method using a salting-out procedure. The effects of formulation variables on the loading efficiency, particle properties, and in-vitro drug release from the microspheres were determined. The type of dispersant, the amount of wetting agent, and initial stirring time used affected the loading efficiency, while the volume of external phase and emulsification speed affected the particle size of the microspheres to a greater extent. The crystal properties of the drug in the wax matrix and the morphology of the microspheres were studied by differential scanning calorimetry (DSC), powder x-ray diffraction (XRD), and scanning electron microscopy (SEM). The DSC thermograms of the microspheres showed that the drug lost its crystallinity during the microencapsulation process, which was further confirmed by the XRD data. The electron micrographs of the drug-loaded microspheres showed well-formed spherical particles with a rough exterior.

  9. 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.

  10. Formulation and evaluation of self-emulsifying orlistat tablet to enhance drug release and in vivo performance: factorial design approach.

    Science.gov (United States)

    Gade, Mukund Maruti; Hurkadale, Pramod Jayadevappa

    2016-06-01

    The purpose of the present research work was to formulate, evaluate, and optimize self-emulsifying orlistat tablet to enhance drug release followed by in vivo antiobesity activity in Wistar rats. Initially, the solubility of orlistat was determined in different natural oils, surfactant, and co-surfactants. Self-emulsifying drug delivery system (SEDDS) was prepared by using castor oil, Tween 80, and Capryol PGMC as components. Liquid SEDDS evaluated for globule size and emulsification time. A 3(2) full factorial design was utilized for the optimization purpose. Formulation variables such as quantity of oil (X1) and ratio of surfactant to co-surfactant (X2) were investigated for their effect on globule size and emulsification time. Optimized formulation with minimum globule size was freeze-dried which further compressed into the tablet. Finally, optimized formulation evaluated for the in vitro drug release study followed by weight losing potential in Wistar rats. Globule size and emulsification time for the optimized formulation were found to be 96.4 ± 8.5 nm and 26 ± 4 s, respectively. Fourier transform infra red spectroscopy (FTIR) studies indicated that there was no interaction between drug and excipients. Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) study revealed that there was the conversion of crystalline orlistat to the amorphous form. Orlistat release from the self-emulsifying tablet formulation was faster with higher weight reduction potential in Wistar rats than the marketed formulation. Increased in vitro drug release with considerable in vivo weight loss by self-emulsifying tablet suggests that the SEDDS could serve as potential formulation strategy for orlistat.

  11. Poly(3-hydroxybutyrate)/metribuzin formulations: characterization, controlled release properties, herbicidal activity, and effect on soil microorganisms.

    Science.gov (United States)

    Volova, Tatiana; Zhila, Natalia; Kiselev, Evgeniy; Prudnikova, Svetlana; Vinogradova, Olga; Nikolaeva, Elena; Shumilova, Anna; Shershneva, Anna; Shishatskaya, Ekaterina

    2016-12-01

    Slow-release formulations of the herbicide metribuzin (MET) embedded in the polymer matrix of degradable poly-3-hydroxybutyrate [P(3HB)] in the form of microparticles, films, microgranules, and pellets were developed and tested. The kinetics of polymer degradation, MET release, and accumulation in soil were studied in laboratory soil microecosystems with higher plants. The study shows that MET release can be controlled by using different techniques of constructing formulations and by varying MET loading. MET accumulation in soil occurs gradually, as the polymer is degraded. The average P(3HB) degradation rates were determined by the geometry of the formulation, reaching 0.17, 0.12, 0.04, and 0.05 mg/day after 60 days for microparticles, films, microgranules, and pellets, respectively. The herbicidal activities of P(3HB)/MET formulations and commercial formulation Sencor Ultra were tested on the Agrostis stolonifera and Setaria macrocheata plants. The parameters used to evaluate the herbicidal activity were plant density and the weight of fresh green biomass measured at days 10, 20, and 30 after sowing. All P(3HB)/MET formulations had pronounced herbicidal activity, which varied depending on MET loading and the stage of the experiment. In the early phases of the experiment, the herbicidal effect of P(3HB)/MET formulations with the lowest MET loading (10 %) was comparable with that of the commercial formulation. The herbicidal effect of P(3HB)/MET formulations with higher MET loadings (25 and 50 %) at later stages of the experiment were stronger than the effect of Sencor Ultra.

  12. Optimizing novel implant formulations for the prolonged release of biopharmaceuticals using in vitro and in vivo imaging techniques.

    Science.gov (United States)

    Beyer, Susanne; Xie, Li; Schmidt, Mike; de Bruin, Natasja; Ashtikar, Mukul; Rüschenbaum, Sabrina; Lange, Christian M; Vogel, Vitali; Mäntele, Werner; Parnham, Michael J; Wacker, Matthias G

    2016-08-10

    As a rapidly growing class of therapeutics, biopharmaceuticals have conquered the global market. Despite the great potential from a therapeutic perspective, such formulations often require frequent injections due to their short half-life. Aiming to establish a parenteral dosage form with prolonged release properties, a biodegradable implant was developed, based on a combination of nanoencapsulation of protein-heparin complexes, creation of a slow release matrix by freeze-drying, and compression using hyaluronan and methylcellulose. In order to investigate this novel delivery system, formulations containing IFN-β-1a and trypsinogen as model proteins were developed. No degradation of the proteins was observed at any stage of the formulation processing. The potential of the delivery system was evaluated in vivo and in vitro after fluorescence-labeling of the biopharmaceuticals. An optimized agarose gel was utilized as in vitro release medium to simulate the subcutaneous environment in a biorelevant manner. In addition, the formulations were administered to female SJL mice and release was innovatively tracked by fluorescence imaging, setting up an in vitro-in vivo correlation. A prolonged time of residence of approximately 12days was observed for the selected formulation design.

  13. Effect of thermal and chemical modifications on the mechanical and release properties of paracetamol tablet formulations containing corn, cassava and sweet potato starches as filler-binders

    Directory of Open Access Journals (Sweden)

    Mariam Vbamiunomhene Lawal

    2015-07-01

    Conclusions: Modification of the experimental starches improved the mechanical and release properties of directly compressed paracetamol tablet formulations. Thus, they can be developed for use as pharmaceutical excipients in specific formulations.

  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. Gradual reduction of testosterone using a gonadotropin-releasing hormone vaccination delays castration resistance in a prostate cancer model

    Science.gov (United States)

    Barranco, Jesús A. Junco; Millar, Robert P.; Fuentes, Franklin; Bover, Eddy; Pimentel, Eulogio; Basulto, Roberto; Calzada, Lesvia; Morán, Rolando; Rodríguez, Ayni; Garay, Hilda; Reyes, Osvaldo; Castro, Maria D.; Bringas, Ricardo; Arteaga, Niurka; Toudurí, Henio; Rabassa, Mauricio; Fernández, Yairis; Serradelo, Andrés; Hernández, Eduardo; Guillén, Gerardo E.

    2016-01-01

    In a previous study aimed to design a novel prostate cancer vaccine, the authors of the present study demonstrated the advantage of combining the adjuvants Montanide ISA 51 with very small size proteoliposomes (VSSP) to promote a significant humoral immune response to gonadotropin-releasing hormone (GnRH) in healthy animals. The present study compared the efficacy of this vaccine formulation versus the standard treatment currently available in terms of preventing the development of tumors in DD/S mice injected with Shionogi carcinoma (SC) 115 cells. The results demonstrated that 5 non-vaccinated control mice exhibited a fast tumor growth, and succumbed to the disease within 19–31 days. Mice immunized with the GnRH/Montanide ISA 51/VSSP vaccine exhibited a moderate decline in testosterone levels that was associated with a decrease in anti-GnRH antibody titers, which lead to a sustained tumor growth inhibition. In total, 2 mice in the immunized group exhibited complete remission of the tumor for the duration of the present study. In addition, castrated mice, which were used as a control for standard hormonal therapy, exhibited an accelerated decrease in tumor size. However, tumor relapse was observed between days 50 and 54, and between days 65 and 85, following the injection of SC 155 cells. Therefore, these mice were sacrificed at day 90. The present study concludes that the slow and moderate reduction of testosterone levels observed using the GnRH-based vaccine may delay the appearance of castration resistance in a Shionogi prostate cancer model. These findings suggest that this vaccine may be used to delay castration resistance in patients with prostate cancer. PMID:27446378

  16. Optimization of metoprolol tartrate modified-release matrix tablet formulation using Eudragit NE as binder for metoprolol fluid bed granulation

    Directory of Open Access Journals (Sweden)

    Ioan Tomuta

    2012-01-01

    Full Text Available The aim of this experimental work was to investigate the possibility of obtaining hydroxypropyl methylcellulose (HPMC hydrophilic matrix extended-release dosage forms with metoprolol by using aqueous dispersions of Eudragit NE, as binders in fluid bed granulation. To evaluate the influence of formulation variables (levels of HPMC-Methocel K100 M and Surelease E7 19010 on drug release during a period of time of 12 hours, and on the kinetic release, a full factorial experimental design with two factors and three levels was used. The formulation factors were the granulation polymer concentration and the matrix-forming polymer concentration. The obtained results have shown that the percentage of the drug released during the 12 hours is influenced both by the Methocel ratio and the Eudragit NE ratio; increasing the ratios of Eudragit and Methocel leads to the decrease of the percentage of the released drug. The influence of Eudragit NE percentage is maximum at four and six hours, but the influence of Methocel K100 M concentration is almost the same at all sampling times; all studied formulations showed a kinetic release that fitted best with the Peppas model.

  17. 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.

  18. Distinct cytokine release profiles from human endothelial and THP-1 macrophage-like cells exposed to different amphotericin B formulations.

    Science.gov (United States)

    Turtinen, Lloyd W; Bremer, Lindsay A; Prall, David N; Schwartzhoff, Jenifer; Hartsel, Scott C

    2005-01-01

    Amphotericin B(AmB) formulations, Fungizone, and Amphotec caused substantially greater proinflammatory cytokine release than AmBisome (L-AMB) and Abelcet in TPA differentiated THP-1 macrophages as determined by antibody based protein arrays. Lipopolysaccharide but not AmB induced significant pro-inflammatory cytokines in human endothelial cells.

  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. 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.

  1. 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.

  2. 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.

  3. Extended release microparticle-in-gel formulation of octreotide: Effect of polymer type on acylation of peptide during in vitro release.

    Science.gov (United States)

    Vaishya, Ravi D; Mandal, Abhirup; Patel, Sulabh; Mitra, Ashim K

    2015-12-30

    Polymeric microparticles (MPs)-in-gel formulations for extended delivery of octreotide were developed. We investigated influence of polymer composition on acylation of octreotide and kinetics of release during in vitro release from biodegradable polymeric formulations. Polycaprolactone (PCL), polylactic acid (PLA), polyglycolic acid (PGA) and polyethylene glycol (PEG) based triblock (TB≈PCL10k-PEG2k-PCL10k) and pentablock (PBA≈PLA3k-PCL7k-PEG2k-PCL7k-PLA3k and PBB≈PGA3k-PCL7k-PEG2k-PCL7k-PGA3k) polymers were investigated. Octreotide was encapsulated in MPs using methanol-oil/water emulsion solvent evaporation method. The particles were characterized for size, morphology, encapsulation efficiency, drug loading and in vitro release. Release samples were subjected to HPLC analysis for quantitation and HPLC-MS analysis for identification of native and chemically modified octreotide adducts. Entrapment efficiency of methanol-oil/water method with TB, PBA and PBB polymers were 45%, 60%, and 82%, respectively. A significant fraction of released octreotide was acylated from lactide and glycolide based PBA (53%) and PBB (92%) polymers. Substantial amount of peptide was not released from PBB polymers after 330 days of incubation. Complete release of octreotide was achieved from TB polymer over a period of 3 months with minimal acylation of peptide (13%). PCL based polymers resulted in minimal acylation of peptide and hence may be suitable for extended peptide and protein delivery. Conversely, polymers having PLA and PGA blocks may not be appropriate for peptide delivery due to acylation and incomplete release.

  4. Combined study of biphasic and zero-order release formulations with dissolution tests and ATR-FTIR spectroscopic imaging.

    Science.gov (United States)

    Wray, Patrick; Li, Jing; Li, Ling Qiao; Kazarian, Sergei G

    2014-07-01

    In this study of multi-layer tablets, the dissolution of biphasic and zero-order release formulations has been studied primarily using attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopic imaging as well as UV-Vis detection of dissolved drug in the effluent stream and USP dissolution testing. Bilayer tablets, containing the excipients microcrystalline cellulose (MCC) and glucose, were used for biphasic release with nicotinamide and buflomedil as model drugs. ATR-FTIR spectroscopic imaging showed the changing component distributions during dissolution. Further experiments studied monolithic and barrier-layered tablets containing hydroxypropyl methylcellulose, MCC and buflomedil dissolving in a USP I apparatus. These data were compared with UV-Vis dissolution profiles obtained online with the ATR flow-through cell. ATR-FTIR imaging data of the biphasic formulations demonstrated that the drug release was affected by excipient ratios and effects such as interference between tablet sections. Tablets placed in the ATR-FTIR flow-through cell exhibited zero-order UV-Vis dissolution profile data at high flow rates, similar to barrier-layered formulations studied using the USP I apparatus. ATR-FTIR spectroscopic imaging provided information regarding the dissolution mechanisms in multi-layer tablets which could assist formulation development. The ability to relate data from USP dissolution tests with that from the ATR-FTIR flow-through cell could help spectroscopic imaging complement dissolution methods used in the industry.

  5. Distribution of dipyridamole in blood components among post-stroke patients treated with extended release formulation.

    Science.gov (United States)

    Serebruany, Victor; Sabaeva, Elena; Booze, Christopher; Atar, Oliver D; Eisert, Christian; Hanley, Dan

    2009-09-01

    Extended release dipyridamole (ERD) is widely used in patients after ischaemic stroke; however, the ability of this antithrombotic agent to be stored in different blood cells has never been explored in post-stroke patients. We hypothesised that since ERD is known to be highly lipophilic, the drug may be present not only in plasma, but also accumulated in platelets, leukocytes, and erythrocytes. Fifteen patients after documented ischaemic stroke were treated with Aggrenox (ERD and low-dose aspirin combination) BID for 30 days, and 12 of them completed the study. ERD concentrations in blood cells and platelet-poor plasma were measured by spectrofluorimetry at Baseline, Day 14, and Day 30 after the initiation of therapy. The background level of spectrofluorometry readings differs slightly among the blood components (132-211 ng/ml) due to the differences in the preparation of samples and cell isolation techniques. As expected, two weeks of ERD therapy produced steady-state plasma concentration of dipyridamole already at Day 14 (1,680 +/- 542 ng/ ml), followed by a slight not significant decrease at one month (1,619 +/- 408 ng/ml). Two weeks of therapy was sufficient to achieve a consistent dipyridamole accumulation in erythrocytes (361 +/- 43 ng/ml), but not in platelets (244 +/- 78 ng/ml), or leukocytes (275 +/- 49 ng/ml). In fact, white blood cells continued dipyridamole intake beyond 14 days period, and this increase (398 +/- 66 ng/ml) was significant (p = 0.02) at 30 days. Treatment with ERD in post-stroke patients resulted not only in achievement of therapeutic plasma dipyridamole concentrations, but also deposition of the drug in erythrocytes and leukocytes, but not in platelets. If confirmed, these data will affect our better understanding of dipyridamole pleiotropy, and may explain long-term benefit of ERD formulation.

  6. 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

  7. Formulation and evaluation of controlled-release of telmisartan microspheres: In vitro/in vivo study

    Directory of Open Access Journals (Sweden)

    Praveen Kumar Gaur

    2014-12-01

    Full Text Available The aim of this work was to design a controlled-release drug-delivery system for the angiotensin-II receptor antagonist drug telmisartan. Telmisartan was encapsulated with different EUDRAGIT polymers by an emulsion solvent evaporation technique and the physicochemical properties of the formulations were characterized. Using a solvent evaporation method, white spherical microspheres with particle sizes of 629.9–792.1 μm were produced. The in vitro drug release was studied in three different pH media (pH 1.2 for 2 hours, pH 6.8 for 4 hours, and pH 7.4 for 18 hours. The formulations were then evaluated for their pharmacokinetic parameters. The entrapment efficiency of these microspheres was between 58.6% and 90.56%. The obtained microspheres showed good flow properties, which were evaluated in terms of angle of repose (15.29–26.32, bulk and tapped densities (0.37–0.53 and 0.43–0.64, respectively, Carr indices and Hausner ratio (12.94–19.14% and 1.14–1.23, respectively. No drug release was observed in the simulated gastric medium up to 2 hours; however, a change in pH from 1.2 to 6.8 increased the drug release. At pH 7.4, formulations with EUDRAGIT RS 100 showed a steady drug release. The microsphere formulation TMRS-3 (i.e., microspheres containing 2-mg telmisartan gave the highest Cmax value (6.8641 μg/mL at 6 hours, which was three times higher than Cmax for telmisartan oral suspension (TOS. Correspondingly, the area under the curve for TMRS-3 was 8.5 times higher than TOS. Particle size and drug release depended on the nature and content of polymer used. The drug release mechanism of the TMRS-3 formulation can be explained using the Higuchi model. The controlled release of drug from TMRS-3 also provides for higher plasma drug content and improved bioavailability.

  8. A New Environmentally Safe Formulation and of Low Cost for Prolonged Release System of Atrazine and Diuron

    Directory of Open Access Journals (Sweden)

    Gracy karla da Rocha Cortes

    2017-07-01

    Full Text Available Diuron and atrazine were incorporated in new formulations developed with the purpose to improve herbicides action through release systems, as well as to reduce the environmental toxicity. A low cost formulation (ALG/ESC was obtained by combining sodium alginate (ALG with fish scales of the Piau fish (ESC from the Leporinus elongatus species. From the crosslinking of ALG/ESC with CaCl2, the formulation ALG/ESC-CaCl2 was obtained. For ALG/ESC-CaCl2, the results are successful, showing a prolonged release of 3.5 and 4.5 days for atrazine and diuron, respectively. Based on parameters of an empirical equation used to fit the herbicide release data, it appears that the release systems of diuron and atrazine from ALG/ESC-CaCl2 are by diffusion processes due to anomalous transport, which did not follow Fick’s laws of diffusion. DOI: http://dx.doi.org/10.17807/orbital.v9i3.994

  9. Formulation of controlled-release capsules of biopharmaceutical classification system I drugs using niacin as a model.

    Science.gov (United States)

    Chuong, Monica C; Palugan, Luca; Su, Tiffany M; Busano, Claudelle; Lee, Ronald; Di Pretoro, Giustino; Shah, Anee

    2010-12-01

    Vitamin B(3) is made up of niacin (nicotinic acid) and its amide, niacinamide. Both have equivalent vitamin activity, but only niacin (not niacinamide) is effective in lowering elevated low-density lipoprotein cholesterol and triglyceride levels in the blood. Administration of an extended-release (ER) oral tablet would frequently encounter food. If hydrogel is used to formulate the matrix of a biopharmaceutical classification system I drug (high solubility and high permeability), the dosage form absorbs water and swells.. The softened outer layer may be slashed off by food present in the stomach, thus, exposing the core tablet more readily for water absorption and speeding up drug release from its original designed rate. This project aimed to formulate niacin CR pellets made of hydrophobic inert matrix. After niacin was melted with excipients and cooled, the mass was extruded and spheronized into pellets. Size distribution and flowability were determined before pellets were filled into hard gelatin capsule. The USP dissolution study revealed that a candidate formulation of 250 mg in strength released similar amount of niacin as its commercial reference, niacin controlled-release 500 mg tablet, in 6 h (223.9 ± 23.8 mg, n = 4 versus 259.4 ± 2.6 mg, n = 3). The differential scanning calorimetry study of the pellets in capsules stored in 40°C for 4 weeks, and the content assay of capsules in 40°C up to 6 months suggested that niacin was stable within the innovative formulation. In vitro release from this innovative ER capsules stored at 40°C up to 4 weeks were also investigated.

  10. 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.

  11. 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.

  12. Bioavailability of a dexlansoprazole delayed-release orally disintegrating tablet: effects of food and mode of administration

    Science.gov (United States)

    Kukulka, Michael; Nudurupati, Sai; Perez, Maria Claudia

    2017-01-01

    Background Dexlansoprazole is a proton pump inhibitor (PPI) approved for use in dual delayed-release capsule and orally disintegrating tablet (ODT) formulations. Aim To assess effects of food, water, and route of administration on the bioavailability of dexlansoprazole 30-mg ODT. Methods Two separate open-label, phase 1, single-dose crossover studies were conducted in healthy adults. In study 1, pharmacokinetic parameters were analyzed in participants receiving dexlansoprazole ODT in a fed or fasted state with and without water. In study 2, the bioavailability of dexlansoprazole after administration via oral syringe or nasogastric (NG) tube, or after swallowing intact with water was compared to ODT administration in the fasted state, swallowed without water. Blood samples for determining dexlansoprazole plasma concentrations and pharmacokinetic parameter estimates were collected before and after dosing. Results Equivalent values for area under the plasma concentration–time curve (AUC) were observed in the fed and fasted states, but the maximum observed plasma concentration (Cmax) was 38% lower in the fed state; therefore, bioequivalence was not achieved. A water rinse following standard ODT administration decreased dexlansoprazole bioavailability, with lower Cmax and AUC values than when ODT was administered without a water rinse. Bioequivalence was demonstrated when comparing the alternative routes of administration, including via oral syringe or NG tube with standard ODT administration. Unlike with a water rinse, bioequivalence to standard ODT administration (i.e., without water) was demonstrated when swallowing the ODT intact with water. Rates of adverse events were comparable irrespective of administration route in the fasted state (6.7%–9.3%) and were 12% higher in the fed state than in the fasted state. Conclusion The AUC from the dexlansoprazole ODT was equivalent when administered in the fed and fasted states. Equivalent systemic exposure to

  13. 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...

  14. Predicting absorption and pharmacokinetic profile of carbamazepine from controlled-release tablet formulation in humans using rabbit model

    Directory of Open Access Journals (Sweden)

    Homšek Irena

    2011-01-01

    Full Text Available Controlled-release (CR pharmaceutical formulations offer several advantages over the conventional, immediate release dosage forms of the same drug, including reduced dosing frequency, decreased incidence and/or intensity of adverse effects, greater selectivity of pharmacological activity, reduced drug plasma fluctuation, and better compliance. After a drug product has been registered, and is already on market, minor changes in formulation might be needed. At the same time, the product has to remain effective and safe for patients that could be confirmed via plasma drug concentrations and pharmacokinetic characteristics. It is challenging to predict human absorption and pharmacokinetic characteristics of a drug based on the in vitro dissolution test and the animal pharmacokinetic data. Therefore, the objective of this study was to establish correlation of the pharmacokinetic parameters of carbamazepine (CBZ CR tablet formulation between the rabbit and the human model, and to establish in vitro in vivo correlation (IVIVC based on the predicted fractions of absorbed CBZ. Although differences in mean plasma concentration profiles were notified, the data concerning the predicted fraction of drug absorbed were almost superimposable. Accordingly, it can be concluded that rabbits may be representative as an in vivo model for predicting the pharmacokinetics of the CR formulation of CBZ in humans.

  15. Utilization of posaconazole oral suspension or delayed-released tablet salvage treatment for invasive fungal infection.

    Science.gov (United States)

    Kim, Jong Hun; Benefield, Russell J; Ditolla, Kali

    2016-11-01

    Posaconazole may be useful for salvage treatment (ST) for invasive fungal infections (IFIs). The aim of this study was to evaluate the efficacy of posaconazole ST with either posaconazole oral suspension (SUS) or delayed-released tablet (TAB) in patients with IFI. A retrospective review of patients who received posaconazole ST for IFI at the University of Utah Health Sciences Center between December 2007 and March 2014 was conducted. A total of 14 episodes of posaconazole ST for proven (9 episodes) and probable (5 episodes) IFI were identified in 14 patients. The median age was 54 years and the majority of patients (64.3%) had underlying haematological diseases. Posaconazole SUS and TAB were used in 11 episodes and 3 episodes respectively. The duration of posaconazole ST ranged from 28 to 370 days with a median of 65 days. Posaconazole ST with TAB achieved favourable serum posaconazole trough concentrations (median 1.4 μg mL(-1) ) compared to posaconazole SUS (median 1.0 μg mL(-1) ). The overall clinical success rate with posaconazole ST was 71.4% (10 of 14 episodes). One patient died of progression of IFI. Adverse events were noted in two patients. Posaconazole SUS or TAB may be used effectively for IFI ST.

  16. Synthesis and Characteristics of Valeric Acid-Zinc Layered Hydroxide Intercalation Material for Insect Pheromone Controlled Release Formulation

    Directory of Open Access Journals (Sweden)

    Rozita Ahmad

    2016-01-01

    Full Text Available A new intercalation compound of insect pheromone, valeric acid (VA, based on zinc layered hydroxide (ZLH as host release material, was successfully prepared through coprecipitation method. The as-produced organic-inorganic nanolayered material, valerate nanohybrid, VAN, shows the formation of a new peak at lower 2θ angle with basal spacing of 19.8 Å with no ZnO reflections, which indicate that the intercalation of anion between the inorganic ZLH interlamellae was accomplished. The elemental, FTIR, and ATR analyses of the nanohybrid supported the fact that the intercalation with the percentage anion loading was calculated to be 23.0% (w/w. The thermal stability property of the resulting nanohybrid was enhanced compared to the unbound anion. Field emission scanning electron micrograph of the ZnO has a nonuniform granular structure but transforms into flake-like structure with various sizes after the intercalation process. Release kinetics of anion from the interlayer of intercalated compound exhibited a slow release behavior governed by the pseudo-second-order kinetic model at different pHs of aqueous media. The valerate anion was released from VAN with the highest release rate at pH 4. These findings provide the basis to further development of controlled release formulation for insect pheromone based on ZLH intercalation.

  17. Oral controlled release formulation for highly water-soluble drugs: drug--sodium alginate--xanthan gum--zinc acetate matrix.

    Science.gov (United States)

    Zeng, W M

    2004-05-01

    An oral controlled release formulation matrix for highly water-soluble drugs was designed and developed to achieve a 24-hour release profile. Using ranitidine HCl as a model drug, sodium alginate formulation matrices containing xanthan gum or zinc acetate or both were investigated. The caplets for these formulations were prepared by direct compression and the in vitro release tests were carried out in simulated intestinal fluid (SIF, pH 7.5) and simulated gastric fluid (SGF, pH 1.2). The release of the drug in the sodium alginate formulation containing only xanthan gum completed within 12 hours in the SIF, while the drug release in the sodium alginate formulation containing only zinc acetate finished almost within 2 hours in the same medium. Only the sodium alginate formulation containing both xanthan gum and zinc acetate achieved a 24-hour release profile, either in the SIF or in the pH change medium. In the latter case, the caplet released in the SGF for 2 hours was immediately transferred into the SIF to continue the release test. The results showed that the presence of both xanthan gum and zinc acetate in sodium alginate matrix played a key role in controlling the drug release for 24 hours. The helical structure and high viscosity of xanthan gum might prevent zinc ions from diffusing out of the ranitidine HCl--sodium alginate--xanthan gum--zinc acetate matrix so that zinc ions could react with sodium alginate to form zinc alginate precipitate with a cross-linking structure. The cross-linking structure might control a highly water-soluble drug to release for 24 hours. Evaluation of the release data showed the release mechanism for the novel formulation might be attributed to the diffusion of the drug.

  18. A novel experimental design method to optimize hydrophilic matrix formulations with drug release profiles and mechanical properties.

    Science.gov (United States)

    Choi, Du Hyung; Lim, Jun Yeul; Shin, Sangmun; Choi, Won Jun; Jeong, Seong Hoon; Lee, Sangkil

    2014-10-01

    To investigate the effects of hydrophilic polymers on the matrix system, an experimental design method was developed to integrate response surface methodology and the time series modeling. Moreover, the relationships among polymers on the matrix system were studied with the evaluation of physical properties including water uptake, mass loss, diffusion, and gelling index. A mixture simplex lattice design was proposed while considering eight input control factors: Polyethylene glycol 6000 (x1 ), polyethylene oxide (PEO) N-10 (x2 ), PEO 301 (x3 ), PEO coagulant (x4 ), PEO 303 (x5 ), hydroxypropyl methylcellulose (HPMC) 100SR (x6 ), HPMC 4000SR (x7 ), and HPMC 10(5) SR (x8 ). With the modeling, optimal formulations were obtained depending on the four types of targets. The optimal formulations showed the four significant factors (x1 , x2 , x3 , and x8 ) and other four input factors (x4 , x5 , x6 , and x7 ) were not significant based on drug release profiles. Moreover, the optimization results were analyzed with estimated values, targets values, absolute biases, and relative biases based on observed times for the drug release rates with four different targets. The result showed that optimal solutions and target values had consistent patterns with small biases. On the basis of the physical properties of the optimal solutions, the type and ratio of the hydrophilic polymer and the relationships between polymers significantly influenced the physical properties of the system and drug release. This experimental design method is very useful in formulating a matrix system with optimal drug release. Moreover, it can distinctly confirm the relationships between excipients and the effects on the system with extensive and intensive evaluations.

  19. In-vitro/in-vivo correlation of pulsatile drug release from press-coated tablet formulations: a pharmacoscintigraphic study in the beagle dog.

    Science.gov (United States)

    Ghimire, Manish; McInnes, Fiona J; Watson, David G; Mullen, Alexander B; Stevens, Howard N E

    2007-09-01

    The aim of the current study was to investigate the in-vitro and in-vivo performance of a press-coated tablet (PCT) intended for time delayed drug release, consisting of a rapidly disintegrating theophylline core tablet, press-coated with barrier granules containing glyceryl behenate (GB) and low-substituted hydroxypropylcellulose (L-HPC). The PCTs showed pulsatile release with a lag time dependent upon the GB and L-HPC composition of the barrier layer. In-vivo gamma-scintigraphic studies were carried out for PCTs containing GB:L-HPC at 65:35 w/w and 75:25 w/w in the barrier layer in four beagle dogs, in either the fed or fasted state. The in-vivo lag time in both the fed and fasted states did not differ significantly (p>0.05) from the in-vitro lag time. Additionally, no significant difference (p<0.05) between in-vivo fed and fasted disintegration times was observed, demonstrating that in-vivo performance of the PCT was not influenced by the presence or absence of food in the gastrointestinal tract. A distinct lag time was obtained prior to the appearance of drug in plasma and correlated (R2=0.98) with disintegration time observed from scintigraphic images. However, following disintegration, no difference in pharmacokinetic parameters (AUC(0-6 dis), K(el), Cmax) was observed. The current study highlighted the potential use of these formulations for chronopharmaceutical drug delivery.

  20. Efficacy and safety of a once-daily extended-release formulation of pramipexole switched from an immediate-release formulation in patients with advanced Parkinson's disease: results from an open-label study.

    Science.gov (United States)

    Takanashi, M; Shimo, Y; Hatano, T; Oyama, G; Hattori, N

    2013-12-01

    This study aimed to evaluate the efficacy and safety of an extended-release tablet formulation of pramipexole (PPX-ER) given once daily when switched from an immediate-release tablet formulation (PPX-IR) given 3 times daily. This open-label study included 29 patients with idiopathic Parkinson's disease (PD) who were followed for 8 weeks. Primary endpoints were Unified Parkinson's Disease Rating Scale (UPDRS) part III score, a physician evaluation of motor symptoms; nocturnal and early morning symptoms (NEMS) score, based on the results for 4 items in the Parkinson's Disease Sleep Scale and the Movement Disorder Society - sponsored revision of the UPDRS; and patients' formulation preference, determined through questionnaires. Secondary endpoints were nocturnal sleep disturbance, evaluated using the revised version of the Parkinson's Disease Sleep Scale (PDSS-2); quality of life, evaluated using the 39-item Parkinson's Disease Questionnaire (PDQ-39); Clinical Global Impression-Improvement (CGI-I) score; Patient Global Impression-Improvement (PGI-I) score; and caregiver formulation preference. UPDRS part III score (mean ± SD) was significantly decreased after 4 weeks (13.9 ± 7.3; P=0.030) and 8 weeks (12.2 ± 7.3; P<0.001) from baseline (15.3 ± 7.0). However, no significant change was found in NEMS scale, PDSS-2 or PDQ-39 scores. After 8 weeks, the responder rates based on CGI-I and PGI-I scores were 27.6% and 20.7%, respectively. As a result of the questionnaire, 63.0% of patients and 58.8% of their caregivers preferred PPX-ER. A non-serious drug-related adverse event (diarrhea) was observed in one patient. In conclusion, PPX-ER can be considered as a useful treatment option when PPX-IR needs to be switched to other dopamine agonists.This study is registered with UMIN-CTR (UMIN000006521).

  1. PCL films incorporated with paclitaxel/5-fluorouracil: Effects of formulation and spacial architecture on drug release.

    Science.gov (United States)

    Rong, Hao-Jun; Chen, Wei-Luan; Guo, Sheng-Rong; Lei, Lei; Shen, Yuan-Yuan

    2012-05-10

    The bi/tri-layered poly(ɛ-caprolactone) (PCL)-based films co-loaded with 5-fluorouracil (5-FU) and paclitaxel (PTX) are presented for biodegradable film-based stent application. A gradient elution HPLC analytical method was used for simultaneous quantification of 5-FU and PTX. Scanning electron microscopy (SEM) was performed to observe the microscopic architecture and morphologies, and X-ray diffraction (XRD) was employed for analyzing the physical state of the components in the single layer film. Horizontal cells diffusion test results indicated that the multi-layered structure endowed the film with drug release in unidirectional pattern. The in vitro release results showed that drug release was dependent on the drug loading, the ratio of 5-FU/PTX, the composition of surface layer, as well as the addition of hydrophilic PEG. The cytotoxicity results indicated that the PCL-based films co-loaded with 5-FU and PTX could effectively inhibit the proliferation of Eca-109 cells. The in vivo drug release results showed that the in vivo drug release was highly correlative with the in vitro drug releases. This study provided PCL-based films co-loaded with 5-FU and PTX with great potential for anti-tumor stent application, due to their unidirectional and rate-tunable drug release characteristics and dual drug loading capacity.

  2. The release and transdermal penetration of baclofen formulated in a poloxamer lecithin organogel.

    Science.gov (United States)

    Arnold, John J; Asbill, Scott

    2009-01-01

    The purpose of this study was to evaluate the in vitro release and ex vivo penetration of baclofen following incorporation into a 2% poloxamer lecithin organogel. Franz cells were utilized for both the release and penetration studies. Semi-permeable dialysis membranes were used as the model skin for the penetration study. Baclofen release and penetration at predetermined time points were assessed using high-performamce liquid chromatographic analysis. Results demonstrated that baclofen release from the poloxamer lecithin organogel was significantly higher than its penetration through porcine skin. The amount of baclofen released by the poloxamer lecithin organogel was linear up to 12 hours. Approximately 20% of applied drug was released over the duration of the study period. In comparison with drug released, the ex vivo penetration of baclofen through porcine skin was very low with only minute detectable quantities (significantly less than 1%) after the 12-hour study period. These results suggest that the request to include baclofen into a compounded poloxamer lecithin organogel should be approached cautiously by compounding pharmacists.

  3. 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.

  4. Polymeric formulations for drug release prepared by hot melt extrusion : application and characterization

    NARCIS (Netherlands)

    Stanković, Milica; Frijlink, Henderik W; Hinrichs, Wouter L J

    2015-01-01

    Over the past few decades hot melt extrusion (HME) has emerged as a powerful processing technology for the production of pharmaceutical solid dosage forms in which an active pharmaceutical ingredient (API) is dispersed into polymer matrices. It has been shown that formulations using HME can provide

  5. Halitosis in cystinosis patients after administration of immediate-release cysteamine bitartrate compared to delayed-release cysteamine bitartrate

    NARCIS (Netherlands)

    Besouw, Martine; Tangerman, Albert; Cornelissen, Elisabeth; Rioux, Patrice; Levtchenko, Elena

    2012-01-01

    Halitosis due to dimethylsulfide (DMS) generation is a major side effect of cysteamine in the treatment of cystinosis. Recently, an enteric coated formulation of cysteamine bitartrate (RP103) administered twice daily was demonstrated to be non-inferior for lowering WBC cystine levels compared to the

  6. Formulation of unidirectional release buccal patches of carbamazepine and study of permeation through porcine buccal mucosa

    Directory of Open Access Journals (Sweden)

    Parthasarathy Govindasamy

    2013-12-01

    Conclusions: The prepared unidirectional buccal patches of carbamazepine provided a maximum drug release within specified mucoadhesion period and it indicates a potential alternative drug delivery system for systemic delivery of carbamazepine.

  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. Delayed release dexlansoprazole in the treatment of GERD and erosive esophagitis

    Directory of Open Access Journals (Sweden)

    Eric T Wittbrodt

    2009-11-01

    Full Text Available Eric T Wittbrodt1, Charles Baum2, David A Peura31Takeda Pharmaceuticals North America, Inc., 2Takeda Pharmaceuticals International, Inc., Deerfield, IL, USA; 3University of Virginia, School of Medicine, Charlottesville, VA, USAAbstract: Although proton pump inhibitors (PPI have a record of remarkable effectiveness and safety in the management of gastroesophageal reflux disease (GERD, several treatment challenges with PPI have emerged. Dexlansoprazole MR is the (R-enantiomer of lansoprazole contained in a formulation that produces two distinct releases of drug and significantly extends the duration of active plasma concentrations and % time pH > 4 beyond that of conventional singlerelease PPI. Dexlansoprazole MR can be administered without regard to meals or the timing of meals in most patients. Dexlansoprazole MR 60 mg demonstrated similar efficacy for healing of erosive esophagitis at 8 weeks compared with lansoprazole 30 mg, and dexlansoprazole MR 30 mg was superior to placebo for maintenance of healed erosive esophagitis at 6 months with 99% of nights and 96% of days heartburn-free over 6 months in patients taking dexlansoprazole MR 30 mg. Superior relief of heartburn occurred in patients taking dexlansoprazole MR 30 mg (55% heartburn-free 24-hour periods vs placebo (14% for symptomatic nonerosive GERD. The safety profile of dexlansoprazole MR is similar to that of lansoprazole. The extended pharmacodynamic effects, added convenience, and efficacy and safety of dexlansoprazole MR offer a novel approach to gastric pH control in patients with acid-related disorders.Keywords: dexlansoprazole MR, gastroesophageal reflux disease, GERD, erosive esophagitis, TAK-390MR

  9. The design of controlled-release formulations resistant to alcohol-induced dose dumping--a review.

    Science.gov (United States)

    Jedinger, N; Khinast, J; Roblegg, E

    2014-07-01

    The concomitant intake of alcoholic beverages together with oral controlled-release opioid formulations poses a serious safety concern since alcohol has the potential to alter the release rate controlling mechanism of the dosage form which may result in an uncontrolled and immediate drug release. This effect, known as alcohol-induced dose dumping, has drawn attention of the regulatory authorities. Thus, the Food and Drug Administration (FDA) recommends that in vitro drug release studies of controlled-release dosage forms containing drugs with narrow therapeutic range should be conducted in ethanolic media up to 40%. So far, only a limited number of robust dosage forms that withstand the impact of alcohol are available and the development of such dosage forms is still a challenge. This review deals with the physico-chemical key factors which have to be considered for the preparation of alcohol-resistant controlling dosage forms. Furthermore, appropriate matrix systems and promising technological strategies, which are suitable to prevent alcohol-induced dose dumping, are discussed.

  10. Effect of the proton pump inhibitor omeprazole on the pharmacokinetics of extended-release formulations of oxybutynin and tolterodine.

    Science.gov (United States)

    Dmochowski, Roger; Chen, Andrew; Sathyan, Gayatri; MacDiarmid, Scott; Gidwani, Shalini; Gupta, Suneel

    2005-08-01

    This study assessed the effect of the proton pump inhibitor omeprazole on the bioavailability of the extended-release formulations of oxybutynin and tolterodine. Forty-four healthy volunteers received each of 4 treatments in a 4-period crossover design. The treatments consisted of osmotically controlled extended-release oxybutynin chloride tablets at 10 mg/d or extended-release tolterodine tartrate capsules at 4 mg/d, with and without preceding treatment with 20 mg omeprazole daily for 4 days. Blood samples collected predose and at scheduled time points for 36 hours postdose were analyzed for oxybutynin and its active metabolite, N-desethyloxybutynin, or tolterodine and its active 5-hydroxymethyl metabolite, as appropriate. The AUCinfinity ratios for oxybutynin and its metabolite with and without prior omeprazole fell within the 80% to 125% range (accepted as the criterion for bioequivalence), as did those for tolterodine and its active moiety. The peak concentration ratios for oxybutynin and metabolite also conformed to this range; those for tolterodine did not. Increasing gastric pH with omeprazole does not substantially alter the pharmacokinetic properties of extended-release oxybutynin but may alter those of extended-release tolterodine.

  11. 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.

  12. 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.

  13. Polymeric formulations for drug release prepared by hot melt extrusion: application and characterization.

    Science.gov (United States)

    Stanković, Milica; Frijlink, Henderik W; Hinrichs, Wouter L J

    2015-07-01

    Over the past few decades hot melt extrusion (HME) has emerged as a powerful processing technology for the production of pharmaceutical solid dosage forms in which an active pharmaceutical ingredient (API) is dispersed into polymer matrices. It has been shown that formulations using HME can provide time-controlled, sustained and targeted drug delivery, and improved bioavailability of poorly soluble drugs. In this review, the basic principles of the HME process are described together with an overview of some of the most common biodegradable and nonbiodegradable polymers used for the preparation of different formulations using this method. Further, the applications of HME in drug delivery and analytical techniques employed to characterize HME products are addressed.

  14. FORMULATION, CHARACTERIZATION AND IN-VITRO RELEASE STUDY OF SILYMARIN NANOSUSPENSION

    OpenAIRE

    Sumathi .R *, Tamizharasi.S, Gopinath.K, Sivakumar.T

    2017-01-01

    Objective: The main objective of this research was to carry out formulation and evaluation of polymeric nanosuspension for silymarin drug by using suitable surfactants to improve its bioavailability. Methods: The silymarin nanosuspension was prepared and lyophilized for enhancing the dissolution of poorly soluble drug. The high pressure homogenization technique was adapted to produce the silymarin nanosuspension respectively using polymers such as Poloxamer188, Poloxamer 407 and Soya lecithin...

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

    OpenAIRE

    Jarag Ravindra Jagannath; Rathod Akash Maroti; Salunkhe Renuka Madhukar; Mangal Manoj Kumar

    2013-01-01

    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...

  16. 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.

  17. Design, synthesis, characterization and drug release kinetics of PAMAM dendrimer based drug formulations

    Science.gov (United States)

    Kurtoglu, Yunus Emre

    The drug release characteristics of G4-polyamidoamine (PAMAM) dendrimer-ibuprofen conjugates with ester, amide, and peptide linkers were investigated, in addition to a linear PEG-ibuprofen conjugate to understand the effect of architecture and linker on drug release. Ibuprofen was directly conjugated to NH2 -terminated dendrimer by an amide bond and OH-terminated dendrimer by an ester bond. A tetra-peptide linked dendrimer conjugate and a linear mPEG-ibuprofen conjugate were also studied for comparison to direct linked dendrimer conjugates. It is demonstrated that the 3-D nanoscale architecture of PAMAM dendrimer-drug conjugates, along with linking chemistry govern the drug release mechanisms as well as kinetics. Understanding these structural effects on their drug release characteristics is crucial for design of dendrimer conjugates with high efficacy such as poly(amidoamine) dendrimer-N-Acetylcysteine conjugates with disulfide linkages. N-Acetylcysteine (NAC) is an anti-inflammatory agent with significant potential for clinical use in the treatment of neuroinflammation, stroke and cerebral palsy. A poly(amidoamine) dendrimer-NAC conjugate that contains a disulfide linkage was synthesized and evaluated for its release kinetics in the presence of glutathione (GSH), Cysteine (Cys), and bovine serum albumin (BSA) at both physiological and lysosomal pH. FITC-labeled conjugates showed that they enter cells rapidly and localize in the cytoplasm of lipopolysaccharide (LPS)-activated microglial cells. The efficacy of the dendrimer-NAC conjugate was measured in activated microglial cells using reactive oxygen species (ROS) assays. The conjugates showed an order of magnitude increase in anti-oxidant activity compared to free drug. When combined with intrinsic and ligand-based targeting with dendrimers, these types of GSH sensitive nanodevices can lead to improved drug release profiles and in vivo efficacy.

  18. Formulation parameters affecting the performance of coated gelatin capsules with pulsatile release profiles.

    Science.gov (United States)

    Bussemer, T; Bodmeier, R

    2003-11-28

    The objective of this study was to develop and evaluate a rupturable pulsatile drug delivery system based on soft gelatin capsules with or without a swelling layer and an external water-insoluble but -permeable polymer coating, which released the drug after a lag time (rupturing of the external polymer coating). The swelling of the gelatin capsule itself was insufficient to rupture the external polymer coating, an additional swelling layer was applied between the capsule and the polymer coating. Croscarmellose sodium (Ac-Di-Sol) was more effective as a swelling agent than low and high molecular weight hydroxypropylmethyl cellulose (HPMC; E5 or K100M). Brittle polymers, such as ethyl cellulose (EC) and cellulose acetate propionate (CAPr), led to a better rupturing and therefore more complete drug release than the flexible polymer coating, Eudragit RS. The lag time of the release system increased with higher polymer coating levels and decreased with the addition of a hydrophilic pore-former, HPMC E5 and also with an increasing amount of the intermediate swelling layer. The water uptake of the capsules was linear until rupture and was higher with CAPr than with EC. Soft gelatin capsule-based systems showed shorter lag times compared to hard gelatin capsules because of the higher hardness/filling state of the soft gelatin capsules. The swelling pressure was therefore more directed to the external polymer coating with the soft gelatin capsules. Typical pulsatile drug release profiles were obtained at lower polymer coating levels, while the release was slower and incomplete at the higher coating levels. CAPr-coated capsules resulted in a more complete release than EC-coated capsules.

  19. Multicentre study of posaconazole delayed-release tablet serum level and association with hepatotoxicity and QTc prolongation.

    Science.gov (United States)

    Pettit, Natasha N; Miceli, Marisa H; Rivera, Christina G; Narayanan, Prasanna P; Perissinotti, Anthony J; Hsu, Meier; Delacruz, Jennifer; Gedrimaite, Zivile; Han, Zhe; Steinbeck, Jennifer; Pisano, Jennifer; Seo, Susan K; Paskovaty, Alla

    2017-08-01

    The association of posaconazole serum concentrations and toxicity is unclear. An assessment of whether levels obtained with the delayed-release tablet (DRT) formulation are correlated with abnormal liver function test (LFT) results and/or QTc prolongation was undertaken. This was a multicentre, retrospective, observational study of adult patients with cancer between 26 November 2013 and 14 November 2014. Patients were included if they received posaconazole DRT with a posaconazole level obtained between days 5 and 14. Clinical data, including demographics, hepatotoxic medications, posaconazole levels, LFTs and QTc intervals, were obtained. Association of factors with changes in LFTs and QTc prolongation was assessed using linear and logistic regression. One hundred and sixty-six study patients were included. The median posaconazole level was 1250 (range 110-4220) ng/mL and the median time until level was 6 (range 5-14) days. There was a statistically significant increase in AST ( P  <   0.001), ALT ( P  <   0.001), alkaline phosphatase (ALK) ( P  <   0.001), total bilirubin (TBILI) ( P  <   0.001) and QTc ( P  =   0.05) from baseline. Posaconazole levels were not associated with increases in AST [β (SE) = -0.33 (2.2), P  =   0.88], log ALT [β (SE) = -0.02 (0.03), P  =   0.63], ALK [β (SE) = 2.2 (2.9), P  =   0.46] and TBILI [β (SE) = -0.01 (0.04), P  =   0.88]. For each additional hepatotoxic medication, there was a mean change in TBILI of 0.13 mg/dL ( P  =   0.02) and ALK of 7.1 U/L ( P  =   0.09). No statistically significant association between posaconazole level and QTc interval prolongation was found. We did not identify an association between posaconazole serum concentrations and LFT elevations or QTc prolongation. However, some LFTs were found to increase with more hepatotoxic medications administered.

  20. Bioavailability of a dexlansoprazole delayed-release orally disintegrating tablet: effects of food and mode of administration

    Directory of Open Access Journals (Sweden)

    Kukulka M

    2017-02-01

    Full Text Available Michael Kukulka, Sai Nudurupati, Maria Claudia Perez Takeda Development Center Americas, Inc., Deerfield, IL, USA Background: Dexlansoprazole is a proton pump inhibitor (PPI approved for use in dual delayed-release capsule and orally disintegrating tablet (ODT formulations.Aim: To assess effects of food, water, and route of administration on the bioavailability of dexlansoprazole 30-mg ODT. Methods: Two separate open-label, phase 1, single-dose crossover studies were conducted in healthy adults. In study 1, pharmacokinetic parameters were analyzed in participants receiving dexlansoprazole ODT in a fed or fasted state with and without water. In study 2, the bioavailability of dexlansoprazole after administration via oral syringe or nasogastric (NG tube, or after swallowing intact with water was compared to ODT administration in the fasted state, swallowed without water. Blood samples for determining dexlansoprazole plasma concentrations and pharmacokinetic parameter estimates were collected before and after dosing. Results: Equivalent values for area under the plasma concentration–time curve (AUC were observed in the fed and fasted states, but the maximum observed plasma concentration (Cmax was 38% lower in the fed state; therefore, bioequivalence was not achieved. A water rinse following standard ODT administration decreased dexlansoprazole bioavailability, with lower Cmax and AUC values than when ODT was administered without a water rinse. Bioequivalence was demonstrated when comparing the alternative routes of administration, including via oral syringe or NG tube with standard ODT administration. Unlike with a water rinse, bioequivalence to standard ODT administration (i.e., without water was demonstrated when swallowing the ODT intact with water. Rates of adverse events were comparable irrespective of administration route in the fasted state (6.7%–9.3% and were 12% higher in the fed state than in the fasted state. Conclusion: The AUC

  1. Cerebral Rhizomucor Infection Treated by Posaconazole Delayed-Release Tablets in an Allogeneic Stem Cell Transplant Recipient

    Directory of Open Access Journals (Sweden)

    Diego O. Andrey

    2017-02-01

    Full Text Available Mucormycosis (zygomycosis is an emerging fungal disease in allogeneic hematopoietic stem cell transplant (allo-HSCT recipients. A 30-year-old woman diagnosed with acute myelomonocytic leukemia and needing allo-HSCT presented pulmonary and cerebral infection due to Rhizomucor pusillus. This fungal infection was treated with surgical treatment and posaconazole delayed-release tablets. This strategy allowed reaching high drug levels that could not be obtained with the posaconazole solution.

  2. Target delivery and controlled release of the chemopreventive drug sulindac by using an advanced layered double hydroxide nanomatrix formulation system.

    Science.gov (United States)

    Minagawa, Keiji; Berber, Mohamed R; Hafez, Inas H; Mori, Takeshi; Tanaka, Masami

    2012-04-01

    Target delivery and controlled release of the chemopreventive drug sulindac that possesses low water solubility present a great challenge for its pharmaceutical industry. Here, we offered an advanced nanomatrix formulation system of sulindac based on layered double hydroxide materials. The X-ray analysis and infrared spectroscopy confirmed the incorporation of sulindac into the gallery of the layered double hydroxides. The incorporation ratios of sulindac were recorded to be 45, 31 and 20 for coprecipitation, anion-exchange and reconstruction techniques, respectively. The scanning electron microscopy showed a nanomatrix-structure of ~50 nm. The release studies of sulindac-nanomatrix showed a 96% controlled release at the small intestine solution during 3 h(s), indicating an enhancement in the dissolution profile of sulindac after the matrix formation. The layered structure of the matrix supplied sulindac with a well-ordered structure and a relatively hydrophobic microenvironment that controlled the guest hydrolysis and reactivity during the release process. The laminar structure of layered double hydroxides offered a safe preservation for sulindac against photodecarboxylation, and enhanced the drug thermal stability from 190 to 230° C. The ionic electrostatic interaction of sulindac through its acidic group with layered double hydroxides demolished the gastrointestinal ulceration.

  3. Development of sol-gel formulations for slow release of phermones

    Science.gov (United States)

    A new type of dispenser for slow-release of semiochemicals and sex pheromones was developed based on sol-gel polymers that can be useful in monitoring, mass trapping, and mating disruption in integrated pest management (IPM). Sol-gel matrices exhibit glass characteristics and allow control of the de...

  4. Comparison of two hydrogel formulations for drug release in ophthalmic lenses.

    Science.gov (United States)

    Paradiso, P; Galante, R; Santos, L; Alves de Matos, A P; Colaço, R; Serro, A P; Saramago, B

    2014-08-01

    In the present work two types of polymers were investigated as drug releasing contact lens materials: a poly-hydroxyethylmethacrylate (pHEMA) based hydrogel and a silicone hydrogel. The silicone hydrogel resulted from the addition of TRIS, a hydrophobic monomer containing silicon (3-tris(trimethylsilyloxy)silylpropyl 2-methylprop-2-enoate), to pHEMA. Both hydrogels were loaded with an antibiotic (levofloxacin) and an antiseptic (chlorhexidine) by soaking in the drug solutions. The hydrogel properties were determined to be within the range demanded for lens materials. The release profiles of both drugs from the hydrogels were obtained and eventual drug/polymer interactions were assessed with the help of Raman spectra. A mathematical model, developed to mimic the eye conditions, was applied to the experimental results in order to predict the in vivo efficacy of the studied systems. The release profiles were compared with those resulting from the application of commercial eyedrops. The pHEMA based hydrogel demonstrated to be the best material to achieve a controlled release of levofloxacin. In the case of chlorhexidine, the silicone hydrogel seems to lead to better results. In both cases, our results suggest that these materials are adequate for the preparation of daily disposable therapeutic contact lenses.

  5. In vitro solubility, dissolution and permeability studies combined with semi-mechanistic modeling to investigate the intestinal absorption of desvenlafaxine from an immediate- and extended release formulation.

    Science.gov (United States)

    Franek, F; Jarlfors, A; Larsen, F; Holm, P; Steffansen, B

    2015-09-18

    Desvenlafaxine is a biopharmaceutics classification system (BCS) class 1 (high solubility, high permeability) and biopharmaceutical drug disposition classification system (BDDCS) class 3, (high solubility, poor metabolism; implying low permeability) compound. Thus the rate-limiting step for desvenlafaxine absorption (i.e. intestinal dissolution or permeation) is not fully clarified. The aim of this study was to investigate whether dissolution and/or intestinal permeability rate-limit desvenlafaxine absorption from an immediate-release formulation (IRF) and Pristiq(®), an extended release formulation (ERF). Semi-mechanistic models of desvenlafaxine were built (using SimCyp(®)) by combining in vitro data on dissolution and permeation (mechanistic part of model) with clinical data (obtained from literature) on distribution and clearance (non-mechanistic part of model). The model predictions of desvenlafaxine pharmacokinetics after IRF and ERF administration were compared with published clinical data from 14 trials. Desvenlafaxine in vivo dissolution from the IRF and ERF was predicted from in vitro solubility studies and biorelevant dissolution studies (using the USP3 dissolution apparatus), respectively. Desvenlafaxine apparent permeability (Papp) at varying apical pH was investigated using the Caco-2 cell line and extrapolated to effective intestinal permeability (Peff) in human duodenum, jejunum, ileum and colon. Desvenlafaxine pKa-values and octanol-water partition coefficients (Do:w) were determined experimentally. Due to predicted rapid dissolution after IRF administration, desvenlafaxine was predicted to be available for permeation in the duodenum. Desvenlafaxine Do:w and Papp increased approximately 13-fold when increasing apical pH from 5.5 to 7.4. Desvenlafaxine Peff thus increased with pH down the small intestine. Consequently, desvenlafaxine absorption from an IRF appears rate-limited by low Peff in the upper small intestine, which "delays" the predicted

  6. Physicochemical properties, in vitro release and skin permeation studies of a topical formulation of standardized pomegranate rind extract.

    Science.gov (United States)

    Mo, Jiao; Kaewnopparat, Nattha; Songkro, Sarunyoo; Panichayupakaranant, Pharkphoom; Reanmongkol, Wantana

    2015-01-01

    The aim of the present study was to develop a stable formulation containing standardized pomegranate rind extracts (SPRE) for topical use in the treatment of dermal diseases. Ellagic acid (EA) as the major active constituent of SPRE (not less than 13%) was quantified by HPLC as an indicator for studies on the stability, in vitro drug release, and skin penetration/retention. The formulation prepared with polyethylene glycols (PEG 400 and PEG 4000) containing 5% SPRE has been found to be stable and provide a release rate of 36.6741±5.0072 μg/cm(2)/h that was best fitted to the zero-order kinetic model. EA from SPRE did not penetrate the full-thickness rat skin but the skin retention of EA was determined to be 2.22±0.16 μg/cm(2) with a total recovery of 95.14±5.51%. The results indicated that this 5% SPRE PEG ointment was of satisfactory physicochemical properties and worth further in vivo investigations.

  7. Piroxicam immediate release formulations: A fasting randomized open-label crossover bioequivalence study in healthy volunteers.

    Science.gov (United States)

    Helmy, Sally A; El-Bedaiwy, Heba M

    2014-11-01

    Piroxicam is a NSAID with analgesic and antipyretic properties, used for the treatment of rheumatoid diseases. The aim of this study was to evaluate the bioequivalence of two brands of piroxicam capsules (20 mg) in 24 Egyptian volunteers. The in vivo study was established according to a single-center, randomized, single-dose, laboratory-blinded, 2-period, 2-sequence, crossover study with a washout period of 3 weeks. Under fasting conditions, 24 healthy male volunteers were randomly selected to receive a single oral dose of one capsule (20 mg) of either test or reference product. Plasma samples were obtained over a 144-hour interval and analyzed for piroxicam by HPLC with UV detection. The pharmacokinetic parameters Cmax , tmax , AUC0-t , AUC0-∞ , Vd /F, Cl/F, and t1/2 were determined from plasma concentration-time profiles. The 90% confidence intervals for the ratio of log transformed values of Cmax , AUC0-t , and AUC0-∞ of the two treatments were within the acceptable range (0.8-1.25) for bioequivalence. From PK perspectives, the two piroxicam formulations were considered bioequivalent, based on the rate and extent of absorption. No adverse events occurred or were reported after a single 20-mg piroxicam and both formulations were well-tolerated.

  8. Novel Controlled Release Polymer-Lipid Formulations Processed by Hot Melt Extrusion.

    Science.gov (United States)

    Maniruzzaman, Mohammed; Islam, Muhammad T; Halsey, Sheelagh; Amin, Devyani; Douroumis, Dennis

    2016-02-01

    The aim of the study was to investigate the effect of novel polymer/lipid formulations on the dissolution rates of the water insoluble indomethacin (INM), co-processed by hot melt extrusion (HME). Formulations consisted of the hydrophilic hydroxypropyl methyl cellulose polymer (HPMCAS) and stearoyl macrogol-32 glycerides-Gelucire 50/13 (GLC) were processed with a twin screw extruder to produce solid dispersions. The extrudates characterized by X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC) and hot stage microscopy (HSM) indicated the presence of amorphous INM within the polymer/lipid matrices. In-line monitoring via near-infrared (NIR) spectroscopy revealed significant peak shifts indicating possible interactions and H-bonding formation between the drug and the polymer/lipid carriers. Furthermore, in vitro dissolution studies showed a synergistic effect of the polymer/lipid carrier with 2-h lag time in acidic media followed by enhanced INM dissolution rates at pH > 5.5.

  9. Influence of β-Cyclodextrin Complexation on Ketoprofen Release from Matrix Formulation

    OpenAIRE

    Shukla Vikesh; Masareddy Rajashree; Anghore Ashok; Manvi Fakkirappa.V.

    2009-01-01

    The main objective of this study was to improve the inclusion formation between Ketoprofen and β-cyclodextrin and thus enhance dissolution profile and bioavailability of the ketoprofen. Solubility studies demonstrated the formation of the ketoprofen-β-cyclodextrin inclusion complex with 1:1 stoichiometry. Equimolecular ketoprofen-β-cyclodextrin solid systems were prepared and characterized by DSC, FTIR and hot stage microscopy. Modification of the release of a ketoprofen from the hydrophilic ...

  10. Hierarchical Theoretical Methods for Understanding and Predicting Anisotropic Thermal Transport Release in Rocket Propellant Formulations

    Science.gov (United States)

    2016-12-08

    solid curve) and continuous indentation (purple curve for loading and green curve for unloading from 30 Å). The Hertzian prediction is shown as the...by the flash method," Report No. UCRL-52565, Lawrence Livermore Laboratory, October 1978. DISTRIBUTION A: Distribution approved for public release...Mass fraction: liquid RDX(blue), intermediate( red), gas phase( green ) In this case we tested the concept of using mass fractions, defined by binning

  11. Influence of operational variables in multi-particulate delayed release systems for colon-targeted drug delivery of celecoxib using extrusion spheronization

    Directory of Open Access Journals (Sweden)

    Sinha V

    2010-01-01

    Full Text Available The present research was aimed to formulate and evaluate pH and time-dependent multiparticulate systems for colon-targeted drug delivery of celecoxib (CXB with maximum drug absorption, reduced peak plasma fluctuations, and minimum potential side effects. Multiple unit delayed release systems of the drug in MCC (Avicel® PH-102 grade were prepared using polymethacrylate polymers (Eudragit® L-100 and RSPO as a granulating binder by the extrusion-spheronization technique and characterized for their shape, size, size distribution, friability, density, and moisture content. In vitro release studies were performed in 0.1N HCl, for first 2 h then further performed in phosphate buffer (pH 6.8 for 24 h. The resulting pellets were prepared by extrusion spheronization using different grades of polymethacrylate polymers as a granulating binder, showing a substantial decrease in drug release in initial 5 h (16.28-16.7% and releasing most of the drug in 12-24 h. The geometric and arithmetic mean diameter ranged from (490 to 780 ΅m and (636 to 734 μm, respectively. The minimum to maximum range for circularity, elongation and rectangle were found to be (0.847±0.009 to 0.965±0.078, (1.036±0.057 to 1.185±0.023, and (0.724±0.041 to 0.791±0.047 respectively showing the proper shape and size of the pellets. The content of CXB in the prepared pellets was observed between 98.70 and 99.47% justifying the uniform drug distribution. The in vitro dissolution studies showed that the retardant effect in initial 5 h and most of the drug release in 24 h depended on the ratio and concentration of different grades of methacrylate polymers used in the formulation. CXB-loaded MUPS prepared by the extrusion-spheronization technique using polymethacrylate polymers showed immense potential for colon-specific drug delivery of the drug.

  12. Development of ligustrazine hydrochloride carboxymethyl chitosan and collagen microspheres: Formulation optimization, characterization, and vitro release.

    Science.gov (United States)

    Lin, Qiang; Huo, Qing; Qin, Yingzhe; Zhao, Zhuo; Tao, Fengyun

    2017-01-02

    This study investigates the preparation of ligustrazine hydrochloride carboxymethyl chitosan and collagen microspheres. This experiment investigates effects of the ratio of carboxymethyl chitosan and collagen blend, water to oil ratio, stirring speed, and other factors on the microsphere properties. The experiment had the following conditions: a 1:2 proportion of carboxymethyl chitosan and collagen, a 1:2 proportion of drugs and materials, a 5:1 proportion of oil phase and water phase, 0.5% of span80, a 600r/min stirring speed, 3 ml of a cross-linking agent, 3 h of cross-linking curing, 1.25 ± 0.05 mm diameter LTH microcapsules, a 54.08% envelop rate, and a 14.16% carrier rate. The microspheres release rate reached 66% within 1 h, then steadily released within 5 h in vitro. The experimental results showed that the ligustrazine hydrochloride microsphere production process was stable and exhibited a good release effect compared with other ligustrazine hydrochloride tablets and pills.

  13. Nanoparticles Containing High Loads of Paclitaxel-Silicate Prodrugs: Formulation, Drug Release, and Anticancer Efficacy.

    Science.gov (United States)

    Han, Jing; Michel, Andrew R; Lee, Han Seung; Kalscheuer, Stephen; Wohl, Adam; Hoye, Thomas R; McCormick, Alon V; Panyam, Jayanth; Macosko, Christopher W

    2015-12-07

    We have investigated particle size, interior structure, drug release kinetics, and anticancer efficacy of PEG-b-PLGA-based nanoparticles loaded with a series of paclitaxel (PTX)-silicate prodrugs [PTX-Si(OR)3]. Silicate derivatization enabled us to adjust the hydrophobicity and hydrolytic lability of the prodrugs by the choice of the alkyl group (R) in the silicate derivatives. The greater hydrophobicity of these prodrugs allows for the preparation of nanoparticles that are stable in aqueous dispersion even when loaded with up to ca. 75 wt % of the prodrug. The hydrolytic lability of silicates allows for facile conversion of prodrugs back to the parent drug, PTX. A suite of eight PTX-silicate prodrugs was investigated; nanoparticles were made by flash nanoprecipitation (FNP) using a confined impingement jet mixer with a dilution step (CIJ-D). The resulting nanoparticles were 80-150 nm in size with a loading level of 47-74 wt % (wt %) of a PTX-silicate, which corresponds to 36-59 effective wt % of free PTX. Cryogenic transmission electron microscopy images show that particles are typically spherical with a core-shell structure. Prodrug/drug release profiles were measured. Release tended to be slower for prodrugs having greater hydrophobicity and slower hydrolysis rate. Nanoparticles loaded with PTX-silicate prodrugs that hydrolyze most rapidly showed in vitro cytotoxicity similar to that of the parent PTX. Nanoparticles loaded with more labile silicates also tended to show greater in vivo efficacy.

  14. A simple and sensitive high-performance liquid chromatography method for determination of ciprofloxacin in bioavailability studies of conventional and gastroretentive prolonged-release formulations

    Directory of Open Access Journals (Sweden)

    Jaber Emami

    2016-01-01

    Conclusion: This validated HPLC method was successfully used for the determination of ciprofloxacin in human plasma following oral administration of controlled release formulation, conventional immediate-release tablets and when administered concomitantly with divalent and trivalent cations such as aluminum-, magnesium-, or calcium-containing products under which the bioavailability of ciprofloxacin is significantly reduced.

  15. 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.

  16. Effect of thermal and chemical modifications on the mechanical and release properties of paracetamol tablet formulations containing corn, cassava and sweet potato starches as filler-binders

    Institute of Scientific and Technical Information of China (English)

    Mariam; Vbamiunomhene; Lawal; Michael; Ayodele; Odeniyi; Oludele; Adelanwa; Itiola

    2015-01-01

    Objective: To investigate the effects of acetylation and pregelatinization of cassava and sweet potato starches on the mechanical and release properties of directly compressed paracetamol tablet formulations in comparison with official corn starch.Methods: The native starches were modified by acetylation and pregelatinization. The tablets were assessed using friability(Fr), crushing strength(Cs), disintegration time(Dt) and dissolution parameters. Results: Starch acetylation produced paracetamol tablets that were stronger and had the best balance of mechanical and disintegration properties, while pregelatinization produced tablets that were more friable but had a better overall strength in relation to disintegration than formulations made from natural starches. Correlations mainly existed between Dt and the dissolution parameters t80, t2 and k1 in the formulations. Conclusions: Modification of the experimental starches improved the mechanical and release properties of directly compressed paracetamol tablet formulations. Thus, they can be developed for use as pharmaceutical excipients in specific formulations.

  17. Effect of thermal and chemical modiifcations on the mechanical and release properties of paracetamol tablet formulations containing corn, cassava and sweet potato starches as ifller-binders

    Institute of Scientific and Technical Information of China (English)

    Mariam Vbamiunomhene Lawal; Michael Ayodele Odeniyi; Oludele Adelanwa Itiola

    2015-01-01

    Objective:To investigate the effects of acetylation and pregelatinization of cassava and sweet potato starches on the mechanical and release properties of directly compressed paracetamol tablet formulations in comparison with official corn starch. Methods: The native starches were modified by acetylation and pregelatinization. The tablets were assessed using friability (Fr), crushing strength (Cs), disintegration time (Dt) and dissolution parameters. Results: Starch acetylation produced paracetamol tablets that were stronger and had the best balance of mechanical and disintegration properties, while pregelatinization produced tablets that were more friable but had a better overall strength in relation to disintegration than formulations made from natural starches. Correlations mainly existed between Dt and the dissolution parameters t80, t2 and k1 in the formulations. Conclusions:Modification of the experimental starches improved the mechanical and release properties of directly compressed paracetamol tablet formulations. Thus, they can be developed for use as pharmaceutical excipients in specific formulations.

  18. Phenolic excipients of insulin formulations induce cell death, pro-inflammatory signaling and MCP-1 release

    Directory of Open Access Journals (Sweden)

    Claudia Weber

    2015-01-01

    Insulin solutions displayed cytotoxic and pro-inflammatory potential caused by phenol or m-cresol. We speculate that during insulin pump therapy phenol and m-cresol might induce cell death and inflammatory reactions at the infusion site in vivo. Inflammation is perpetuated by release of MCP-1 by activated monocytic cells leading to enhanced recruitment of inflammatory cells. To minimize acute skin complications caused by phenol/m-cresol accumulation, a frequent change of infusion sets and rotation of the infusion site is recommended.

  19. Controlled-release formulation of antihistamine based on cetirizine zinc-layered hydroxide nanocomposites and its effect on histamine release from basophilic leukemia (RBL-2H3 cells

    Directory of Open Access Journals (Sweden)

    Hussein Al Ali SH

    2012-07-01

    Full Text Available Samer Hasan Hussein Al Ali,1 Mothanna Al-Qubaisi,2 Mohd Zobir Hussein,1,3 Maznah Ismail,2,4 Zulkarnain Zainal,1 Muhammad Nazrul Hakim51Department of Chemistry, Faculty of Science, 2Laboratory of Molecular Biomedicine, Institute of Bioscience, 3Advanced Materials and Nanotechnology Laboratory, Institute of Advanced Technology (ITMA, 4Department of Nutrition and Dietetics, Faculty of Medicine and Health Science, Universiti Putra, Malaysia; 5Department of Biomedical Science, Faculty of Medicine and Health Science, Universiti Putra Malaysia, Selangor, MalaysiaAbstract: A controlled-release formulation of an antihistamine, cetirizine, was synthesized using zinc-layered hydroxide as the host and cetirizine as the guest. The resulting well-ordered nanolayered structure, a cetirizine nanocomposite "CETN," had a basal spacing of 33.9 Å, averaged from six harmonics observed from X-ray diffraction. The guest, cetirizine, was arranged in a horizontal bilayer between the zinc-layered hydroxide (ZLH inorganic interlayers. Fourier transform infrared spectroscopy studies indicated that the intercalation takes place without major change in the structure of the guest and that the thermal stability of the guest in the nanocomposites is markedly enhanced. The loading of the guest in the nanocomposites was estimated to be about 49.4% (w/w. The release study showed that about 96% of the guest could be released in 80 hours by phosphate buffer solution at pH 7.4 compared with about 97% in 73 hours at pH 4.8. It was found that release was governed by pseudo-second order kinetics. Release of histamine from rat basophilic leukemia cells was found to be more sensitive to the intercalated cetirizine in the CETN compared with its free counterpart, with inhibition of 56% and 29%, respectively, at 62.5 ng/mL. The cytotoxicity assay toward Chang liver cells line show the IC50 for CETN and ZLH are 617 and 670 µg/mL, respectively.Keywords: cetirizine hydrochloric acid

  20. Therapeutically optimized rates of drug release can be achieved by varying the drug-to-lipid ratio in liposomal vincristine formulations.

    Science.gov (United States)

    Johnston, Michael J W; Semple, Sean C; Klimuk, Sandra K; Edwards, Katarina; Eisenhardt, Merete L; Leng, Esther C; Karlsson, Göran; Yanko, Daniel; Cullis, Pieter R

    2006-01-01

    The anti-tumor efficacy of liposomal formulations of cell cycle dependent anticancer drugs is critically dependent on the rates at which the drugs are released from the liposomes. Previous work on liposomal formulations of vincristine have shown increasing efficacy for formulations with progressively slower release rates. Recent work has also shown that liposomal formulations of vincristine with higher drug-to-lipid (D/L) ratios exhibit reduced release rates. In this work, the effects of very high D/L ratios on vincristine release rates are investigated, and the antitumor efficacy of these formulations characterized in human xenograft tumor models. It is shown that the half-times (T(1/2)) for vincristine release from egg sphingomyelin/cholesterol liposomes in vivo can be adjusted from T(1/2) = 6.1 h for a formulation with a D/L of 0.025 (wt/wt) to T(1/2) = 117 h (extrapolated) for a formulation with a D/L ratio of 0.6 (wt/wt). The increase in drug retention at the higher D/L ratios appears to be related to the presence of drug precipitates in the liposomes. Variations in the D/L ratio did not affect the circulation lifetimes of the liposomal vincristine formulations. The relationship between drug release rates and anti-tumor efficacy was evaluated using a MX-1 human mammary tumor model. It was found that the antitumor activity of the liposomal vincristine formulations increased as D/L ratio increased from 0.025 to 0.1 (wt/wt) (T(1/2) = 6.1-15.6 h respectively) but decreased at higher D/L ratios (D/L = 0.6, wt/wt) (T(1/2) = 117 h). Free vincristine exhibited the lowest activity of all formulations examined. These results demonstrate that varying the D/L ratio provides a powerful method for regulating drug release and allows the generation of liposomal formulations of vincristine with therapeutically optimized drug release rates.

  1. Aerosol-Assisted Fast Formulating Uniform Pharmaceutical Polymer Microparticles with Variable Properties toward pH-Sensitive Controlled Drug Release

    Directory of Open Access Journals (Sweden)

    Hong Lei

    2016-05-01

    Full Text Available Microencapsulation is highly attractive for oral drug delivery. Microparticles are a common form of drug carrier for this purpose. There is still a high demand on efficient methods to fabricate microparticles with uniform sizes and well-controlled particle properties. In this paper, uniform hydroxypropyl methylcellulose phthalate (HPMCP-based pharmaceutical microparticles loaded with either hydrophobic or hydrophilic model drugs have been directly formulated by using a unique aerosol technique, i.e., the microfluidic spray drying technology. A series of microparticles of controllable particle sizes, shapes, and structures are fabricated by tuning the solvent composition and drying temperature. It is found that a more volatile solvent and a higher drying temperature can result in fast evaporation rates to form microparticles of larger lateral size, more irregular shape, and denser matrix. The nature of the model drugs also plays an important role in determining particle properties. The drug release behaviors of the pharmaceutical microparticles are dependent on their structural properties and the nature of a specific drug, as well as sensitive to the pH value of the release medium. Most importantly, drugs in the microparticles obtained by using a more volatile solvent or a higher drying temperature can be well protected from degradation in harsh simulated gastric fluids due to the dense structures of the microparticles, while they can be fast-released in simulated intestinal fluids through particle dissolution. These pharmaceutical microparticles are potentially useful for site-specific (enteric delivery of orally-administered drugs.

  2. Development of a new single dose extended release formulation of cefpodoxime proxetil

    Institute of Scientific and Technical Information of China (English)

    Deepa Karthikeyan; Karthikeyan M

    2010-01-01

    Objective:To develop floating microspheres of cefpodoxime proxetil (CP) in order to achieve an extended retention in the upper GIT for 12 hour.Methods: The microspheres were prepared by non aqueous solvent evaporation method using different ratios of cefpodoxime proxetil, hydroxyl propyl methyl cellulose (HPMC K4M ) and ethyl cellulose (1:1:1, 1:1:2, 1:1:3, 1:1:4, 1:1:5 & 1:1:6), in the mixture of dichloromethane and ethanol at ratio of (1:1),with tween80 as the surfactant.Results: The floating microspheres was extended over 10-12 hours and were characterized by particle size analysis (75-600毺m), buoyancy percentage (68.1%-85.4%), drug entrapment efficiency (67.5%-88.8%), % yield (50.50%-77.31%) andin vitro drug release was studied for 12 hours.Conclusions: The floating microspheres show better result and it may be use full for prolong the drug release in stomach and improve the bioavailability.

  3. Comparator pH study to evaluate the single-dose pharmacodynamics of dual delayed-release dexlansoprazole 60 mg and delayed-release esomeprazole 40 mg

    Directory of Open Access Journals (Sweden)

    Kukulka M

    2011-09-01

    Full Text Available Michael Kukulka1, Corey Eisenberg2, Sai Nudurupati31Clinical Pharmacology, 2Clinical Science, 3Statistics, Takeda Global Research & Development Center Inc, Deerfield, IL, USABackground: This paper describes a Phase 1, single-center, randomized, open-label, two-period crossover study which compared the pharmacodynamic effects of single doses of dexlansoprazole modified-release 60 mg and esomeprazole 40 mg on 24-hour intragastric pH in healthy adult subjects.Methods: Forty-four subjects aged 20–54 years were randomized in a 1:1 ratio to two sequence groups defining the order in which they received dexlansoprazole and esomeprazole in periods 1 and 2. Primary pharmacodynamic end points over 24 hours postdose were percentage of time with intragastric pH > 4 and mean pH, and secondary pharmacodynamic end points were percentage of time intragastric pH > 4, and mean pH at 0–12 hours, and at >12–24 hours postdose. Each drug was given after an overnight fast and one hour before breakfast. Continuous pH recording began immediately before dosing through to 24 hours postdose.Results: At 0–24 hours postdose, the mean percentage of time with pH > 4 for dexlansoprazole and esomeprazole was 58% and 48%, respectively; the difference was statistically significant (P = 0.003. The average of mean pH values at 0–24 hours postdose for dexlansoprazole and esomeprazole were 4.3 and 3.7, respectively; the difference was statistically significant (P < 0.001. At >12–24 hours postdose, mean percentage of time with pH > 4 and average of mean pH were greater for dexlansoprazole (60% and 4.5, respectively compared with esomeprazole (42% and 3.5, respectively; the difference was statistically significant (P < 0.001 for both intervals. At 0–12 hours postdose, the difference in dexlansoprazole and esomeprazole values for the pharmacodynamic end points was not statistically significant.Conclusion: For the entire 24-hour postdose period, predominantly resulting from

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

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    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.

  5. In vitro release and antiinflammatory activity of topical formulations of ketoprofen.

    Science.gov (United States)

    Moretti, M D; Gavini, E; Peana, A T

    2000-01-01

    Ketoprofen (KP) is a potent nonsteroidal anti-inflammatory drug (NSAID) widely used in clinical practice for the control of acute and chronic pain of soft tissues and skeletal muscle system. The importance of KP in the therapeutic field, has stimulated the development of topical dosage forms to improve its percutaneous absorption through the application site. Moreover they could provide relatively consistent drug levels for prolonged periods and avoid gastric irritation, typical side effect of NSAID oral administration. Since the topical formulation efficiency depends on vehicle characteristics, some different ointments, at 1% and 5% concentrations of KP, were evaluated by in vitro and in vivo studies. Among tested ointments, 1% Carbopol cream and 5% Carbopol gel showed the best fluxes of drug through regenerated cellulose membrane. The in vivo percutaneous absorption of KP, evaluated by carrageenan-induced paw edema in rats, showed a good correlation with the in vitro results about considered creams, but the gels in vivo activity was not in according to their in vitro behaviour. The extemporaneous Carbopol cream was able to produce a better edema inhibition than the commercial one, taken as a reference and widely utilized as a topical therapeutic item. About gels, the obtained results were nearly the maximum response considered possible for a topical antiinflammatory drug.

  6. 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.

  7. Antibody array-generated profiles of cytokine release from THP-1 leukemic monocytes exposed to different amphotericin B formulations.

    Science.gov (United States)

    Turtinen, Lloyd W; Prall, David N; Bremer, Lindsay A; Nauss, Rachel E; Hartsel, Scott C

    2004-02-01

    Cytokine antibody arrays were used to establish the profiles of cytokine release from THP-1 monocytes exposed to different amphotericin B (AMB) drug delivery systems. Fungizone (FZ) and Amphotec (ABCD) caused the release of significantly more inflammatory molecules and the release of inflammatory molecules at higher levels than either AmBisome (L-AMB) or Abelcet (ABLC) after 6 h of treatment. Specifically, tumor necrosis factor alpha (TNF-alpha), interleukin-8 (IL-8), GRO-(alphabetagamma), monocyte chemoattractant protein-1 (MCP-1), RANTES, IL-10, and IL-6 were detected and semiquantified with a chemiluminscence imaging system. TNF-alpha, IL-8, and MCP-1 were the most predominant; however, little if any TNF-alpha was present in ABLC- or L-AMB-treated cultures. The TNF- alpha and IL-8 levels determined by quantitative enzyme-linked immunosorbent assay correlated with the relative cytokine levels measured by using the antibody arrays. Although the viabilities of THP-l monocytes in all AMB-treated cultures were similar by trypan blue exclusion, the amount of lactic dehydrogenase released was significantly larger in FZ- and ABCD-treated cultures than in L-AMB- and ABLC-treated cultures, indicating more membrane perturbations with those formulations. Membrane cation channel formation was also measured in model cholesterol-containing large unilamellar vesicles to directly assess the ion channel formation ability of the system. Only FZ and ABCD induced significant ion currents at concentrations less than 1.5 x 10(-5) M. These results may help provide rationales for the immediate cytokine-mediated side effects observed with FZ and ABCD and the reduced side effects observed with L-AMB and ABLC.

  8. Sustained reduction of diversion and abuse after introduction of an abuse deterrent formulation of extended release oxycodone.

    Science.gov (United States)

    Severtson, Stevan Geoffrey; Ellis, Matthew S; Kurtz, Steven P; Rosenblum, Andrew; Cicero, Theodore J; Parrino, Mark W; Gilbert, Michael K; Buttram, Mance E; Dasgupta, Nabarun; BucherBartelson, Becki; Green, Jody L; Dart, Richard C

    2016-11-01

    The development of abuse deterrent formulations is one strategy for reducing prescription opioid misuse and abuse. A putative abuse deterrent formulation of oxycodone extended release (OxyContin(®)) was introduced in 2010. Early reports demonstrated reduced abuse and diversion, however, an analysis of social media found 32 feasible methods to circumvent the abuse deterrent mechanism. We measured trends of diversion, abuse and street price of OxyContin to assess the durability of the initial reduction in abuse. Data from the Poison Center Program, Drug Diversion Program, Opioid Treatment Program, Survey of Key Informant Patients Program and StreetRx program of the Researched Abuse, Diversion, and Addiction-Related Surveillance (RADARS(®)) System were used. The average quarterly rates of abuse and diversion for OxyContin were compared from before reformulation to the rate in second quarter 2015. Rates were adjusted for population using US Census data and drug availability. OxyContin abuse and diversion declined significantly each quarter after reformulation and persisted for 5 years. The rate of abuse of other opioid analgesics increased initially and then decreased, but to lesser extent than OxyContin. Abuse through both oral and non-oral routes of self-administration declined following the reformulation. The geometric mean difference in the street price of reformulated OxyContin was 36% lower than the reformulated product in the year after reformulation. Despite methods to circumvent the abuse deterrent mechanism, abuse and diversion of OxyContin decreased promptly following the introduction of a crush- and solubility- resistant formulation and continued to decrease over the subsequent 5 years. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  9. Current and future development of extended-release, abuse-deterrent opioid formulations in the United States.

    Science.gov (United States)

    Webster, Lynn R; Markman, John; Cone, Edward J; Niebler, Gwendolyn

    2017-01-01

    Prescription opioid misuse and abuse in the United States (US) is epidemic and is a major burden on health-care resources and costs to society. The need to significantly reduce the risks of prescription opioid misuse and abuse must be balanced with the important needs of patients with chronic pain who may benefit from treatment with opioids. The use of abuse-deterrent formulations (ADFs) of prescription opioids is one approach that could reduce the risk of prescription opioid abuse and misuse while maintaining access to opioids. ADF opioids have properties that make their abuse more difficult, less attractive, or less rewarding. In 2015, the US Food and Drug Administration issued final guidance to industry for the development of ADF opioids that recommended specific studies be conducted to demonstrate the abuse-deterrent properties of new opioid formulations. The technologies and the preclinical and clinical development of ADF opioids are rapidly evolving. This review provides an overview of the required testing for product labeling that includes language about the abuse-deterrent features of an ADF opioid. The objective of this review is to inform and help health-care providers understand the unique development of extended-release ADF opioids and their place in the treatment of patients with pain.

  10. Comparison of single-dose and multiple-dose pharmacokinetics between two formulations of hydrocodone bitartrate/acetaminophen: immediate-release versus biphasic immediate- release/extended release

    Directory of Open Access Journals (Sweden)

    Devarakonda K

    2015-09-01

    Full Text Available Krishna Devarakonda,1 Kenneth Kostenbader,2 Michael J Giuliani,3 Jim L Young4 1Department of Clinical Pharmacology, Mallinckrodt Pharmaceuticals, Hazelwood, MO, USA; 2Independent Pharmaceuticals Professional, Mallinckrodt Pharmaceuticals, Hazelwood, MO, USA; 3Research and Development, 4Clinical Affairs and Program Management, Mallinckrodt Pharmaceuticals, Hazelwood, MO, USA Objective: This study aimed to compare the single-dose and steady-state pharmacokinetics (PK of biphasic immediate-release (IR/extended-release (ER hydrocodone bitartrate (HB/acetaminophen (APAP and IR HB/APAP. Setting: The study was conducted in a contract research center. Participants: The study included healthy adults. Interventions: In a three-way crossover study, Study 1, participants received the following treatments: (A1 a single dose of IR/ER HB/APAP 7.5/325 mg one tablet, followed by one tablet every 12 hours (q12h; (B1 a single dose of IR/ER HB/APAP 7.5/325 mg two tablets, followed by two tablets q12h; (C1 a single dose of IR HB/APAP 7.5/325 mg two tablets (one tablet at hours 0 and 6, followed by one tablet q6h. In a two-way crossover study, Study 2, participants received the following treatments: (A2 an initial dose of IR/ER HB/APAP 7.5/325 mg three tablets, followed by two tablets q12h; (B2 three doses of IR HB/APAP 7.5/325 mg one tablet q4h, followed by one tablet q6h. Main outcome measures: PK values were compared, and adverse events were assessed. Results: Single-dose and steady-state area under the concentration–time curves for hydrocodone and APAP were similar for IR/ER and IR HB/APAP; the steady-state peak plasma concentrations (Cmax at steady state were also similar, but single-dose Cmax for hydrocodone was lower for IR/ER HB/APAP. For most PK parameters, 90% confidence intervals for geometric least squares mean ratios were not meaningfully different (80%–125%. Steady state was achieved in 2-3 days for IR/ER HB/APAP and in 2 days for IR HB/APAP. Median

  11. Effect of PVA on the gel temperature of MC and release kinetics of KT from MC based ophthalmic formulations.

    Science.gov (United States)

    Bain, Mrinal Kanti; Bhowmick, Biplab; Maity, Dipanwita; Mondal, Dibyendu; Mollick, Md Masud Rahaman; Paul, Bijan Kumar; Bhowmik, Manas; Rana, Dipak; Chattopadhyay, Dipankar

    2012-04-01

    The effect of molecular weight of poly(vinyl alcohol) (PVA) and sodium chloride on the gelation temperature of methylcellulose (MC) was studied with the objective to develop a MC based formulation for sustained delivery of ketorolac tromethamine a model ophthalmic drug. Pure MC showed sol-gel transition at 61.2 °C. In order to reduce the gelation temperature of MC and to increase the drug release time, PVA was used. Different techniques such as test tube tilting method, UV-vis spectroscopy, viscometry and rheometry were used to measure gelation temperature of all the binary combinations of MC and PVA. It was observed that the gelation temperature of MC was reduced with the addition of 4% PVA and also the extent of reduction of the gelation temperature of MC was dependent on the molecular weight of PVA. The strong interactions between MC and PVA molecules were established using Fourier transform infrared spectroscopy. To study the in vitro drug release properties of the MC-PVA binary combinations, 6% sodium chloride was used to reduce the gelation temperature further up to physiological temperature. It was observed that the drug release time increased from 5 to 8h with the increase of molecular weight of PVA from 9×10(3) to 1.3×10(5) and this was due to the higher viscosity, better gel strength and greater interactions between the drug and PVA molecules in case of PVA (1.3×10(5)) compared to PVA (9×10(3)). In order to have an idea about the nature of interactions between the functional moieties of the drug and the polymer unit of PVA, a theoretical study was carried out.

  12. Quality of Life is Improved and Kidney Function Preserved in Patients with Nephropathic Cystinosis Treated for 2 Years with Delayed-Release Cysteamine Bitartrate

    NARCIS (Netherlands)

    Langman, C.B.; Greenbaum, L.A.; Grimm, P.; Sarwal, M.; Niaudet, P.; Deschenes, G.; Cornelissen, E.A.M.; Morin, D.; Cochat, P.; Elenberg, E.; Hanna, C.; Gaillard, S.; Bagger, M.J.; Rioux, P.

    2014-01-01

    OBJECTIVES: To determine the long-term effects of delayed-release cysteamine bitartrate (DR-CYS) based on our previous work that established the short-term noninferiority of DR-CYS every 12 hours compared with immediate-release cysteamine bitartrate every 6 hours. STUDY DESIGN: We conducted a prospe

  13. Development of controlled release formulations of carbofuran and imidacloprid and their bioefficacy evaluation against aphid, Aphis gossypii and leafhopper, Amrasca biguttula biguttula Ishida on potato crop.

    Science.gov (United States)

    Kumar, Jitendra; Shakil, N A; Khan, M A; Malik, Kamlesh; Walia, Suresh

    2011-01-01

    Controlled release (CR) formulations of carbofuran and imidacloprid were prepared employing polyvinyl chloride and carboxymethyl cellulose (CMC) and their bioefficacy was evaluated against the aphid, Aphis gossypii and leafhopper, Amrasca biguttula biguttula Ishida on potato crop. The CR formulations of carbofuran and imidacloprid provided better or equal control of the pests than commercial formulations. CMC-based formulation provided a superior control of both the pests. The Imida-CMC, which showed the lowest population of leaf hopper (10.50 leafhopper/100 cl), provided significantly superior control among all treatments after 35 days after germination (DAG). The residue of carbofuran and imidacloprid in potato tuber and soils were not detectable at the time of harvesting in any one of the formulations.

  14. Development and validation of an in vitro–in vivo correlation (IVIVC model for propranolol hydrochloride extended-release matrix formulations

    Directory of Open Access Journals (Sweden)

    Chinhwa Cheng

    2014-06-01

    Full Text Available The objective of this study was to develop an in vitro–in vivo correlation (IVIVC model for hydrophilic matrix extended-release (ER propranolol dosage formulations. The in vitro release characteristics of the drug were determined using USP apparatus I at 100 rpm, in a medium of varying pH (from pH 1.2 to pH 6.8. In vivo plasma concentrations and pharmacokinetic parameters in male beagle dogs were obtained after administering oral, ER formulations and immediate-release (IR commercial products. The similarity factor f2 was used to compare the dissolution data. The IVIVC model was developed using pooled fraction dissolved and fraction absorbed of propranolol ER formulations, ER-F and ER-S, with different release rates. An additional formulation ER-V, with a different release rate of propranolol, was prepared for evaluating the external predictability. The results showed that the percentage prediction error (%PE values of Cmax and AUC0–∞ were 0.86% and 5.95%, respectively, for the external validation study. The observed low prediction errors for Cmax and AUC0–∞ demonstrated that the propranolol IVIVC model was valid.

  15. Colorectal distention induces acute and delayed visceral hypersensitivity: role of peripheral corticotropin-releasing factor and interleukin-1 in rats.

    Science.gov (United States)

    Nozu, Tsukasa; Kumei, Shima; Miyagishi, Saori; Takakusaki, Kaoru; Okumura, Toshikatsu

    2015-12-01

    Most studies evaluating visceral sensation measure visceromotor response (VMR) to colorectal distention (CRD). However, CRD itself induces visceral sensitization, and little is known about the detailed characteristics of this response. The present study tried to clarify this question. VMR was determined by measuring abdominal muscle contractions as a response to CRD in rats. The CRD set consisted of two isobaric distentions (60 mmHg for 10 min twice, with a 30-min rest), and the CRD set was performed on two separate days, i.e., days 1 and 3, 8. On day 1, VMR to the second CRD was increased as compared with that to the first CRD, which is the acute sensitization. VMR to the first CRD on day 3 returned to the same level as that to the first CRD on day 1, and total VMR, i.e., the whole response to the CRD set, was not different between day 1 and day 3. However, total VMR was significantly increased on day 8 as compared with that on day 1, suggesting CRD induced the delayed sensitization. Intraperitoneally administered astressin (200 µg/kg), a corticotropin-releasing factor receptor antagonist, at the end of the first CRD blocked the acute sensitization, but anakinra (20 mg/kg, intraperitoneally), an interleukin-1 receptor antagonist, did not modify it. Astressin (200 µg/kg, twice before CRD on day 8) did not alter the delayed sensitization, but anakinra (20 mg/kg, twice) abolished it. CRD induced both acute sensitization and delayed sensitization, which were mediated through peripheral corticotropin-releasing factor and interleukin-1 pathways, respectively.

  16. The delayed-release combination of doxylamine and pyridoxine (Diclegis®/Diclectin ®) for the treatment of nausea and vomiting of pregnancy.

    Science.gov (United States)

    Madjunkova, Svetlana; Maltepe, Caroline; Koren, Gideon

    2014-06-01

    Nausea and vomiting of pregnancy (NVP) affects up to 85 % of all pregnancies. Effective treatment can greatly improve a woman's quality of life, reduce the risk for maternal and fetal complications, and reduce healthcare costs. Unfortunately, many women receive either no pharmacological treatment or are recommended therapies for which fetal safety and efficacy have not been established. First-line treatment of NVP, as recommended by several leading healthcare and professional organizations, is the combination of doxylamine and pyridoxine. This combination, formulated as a 10 mg/10 mg delayed-release tablet, was approved by the US Food and Drug Administration (FDA) for the treatment of NVP in April 2013 under the brand name Diclegis(®), and has been on the Canadian market since 1979, currently under the brand name Diclectin(®). The efficacy of Diclegis(®)/Diclectin(®) has been demonstrated in several clinical trials, and, more importantly, studies on more than 200,000 women exposed to doxylamine and pyridoxine in the first trimester of pregnancy have demonstrated no increased fetal risk for congenital malformations and other adverse pregnancy outcomes. The present review aims to present the scientific evidence on the effectiveness and fetal safety of Diclegis(®)/Diclectin(®) for the treatment of NVP to justify its use as first-line treatment for NVP.

  17. Are Branded and Generic Extended-Release Ropinirole Formulations Equally Efficacious? A Rater-Blinded, Switch-Over, Multicenter Study

    Directory of Open Access Journals (Sweden)

    Edit Bosnyák

    2014-01-01

    Full Text Available The aim of this study was to compare the efficacy of the branded and a generic extended-release ropinirole formulation in the treatment of advanced Parkinson’s disease (PD. Of 22 enrolled patients 21 completed the study. A rater blinded to treatment evaluated Unified Parkinson’s Disease Rating Scale, Fahn-Tolosa-Marin Tremor Rating Scale, Nonmotor Symptoms Assessment Scale, and a structured questionnaire on ropinirole side effects. Besides, the patients self-administered EQ-5D, Parkinson’s Disease Sleep Scale (PDSS-2, and Beck Depression Inventories. Branded and generic ropinirole treatment achieved similar scores on all tests measuring severity of motor symptoms (primary endpoint, UPDRS-III: 27.0 versus 28.0 points, P=0.505. Based on patient diaries, the lengths of “good time periods” were comparable (10.5 and 10.0 hours for branded and generic ropinirole, resp., P=0.670. However, generic ropinirole therapy achieved almost 3.0 hours shorter on time without dyskinesia (6.5 versus. 9.5 hours, P<0.05 and 2.5 hours longer on time with slight dyskinesia (3.5 versus. 1.0 hours, P<0.05 than the branded ropinirole did. Except for gastrointestinal problems, nonmotor symptoms were similarly controlled. Patients did not prefer either formulation. Although this study has to be interpreted with limitations, it demonstrated that both generic and branded ropinirole administration can achieve similar control on most symptoms of PD.

  18. Role of Gonadotropin-releasing Hormone Stimulation Test in Diagnosing Gonadotropin Deficiency in Both Males and Females with Delayed Puberty

    Institute of Scientific and Technical Information of China (English)

    Qi-Hong Sun; Yu Zheng; Xiao-Lin Zhang; Yi-Ming Mu

    2015-01-01

    Background:Delayed puberty can result either from constitutional delay of growth and puberty (CDP) or idiopathic hypogonadotropic hypogonadism (IHH).Gonadotropin-releasing hormone (GnRH) stimulation test has been generally accepted as a current method for diagnosing delayed puberty.The objective of this research was to assess the cut-off values and the efficacy of GnRH stimulation test in the diagnosis of delayed puberty in both males and females.Methods:A study of 91 IHH,27 CDP patients,6 prepubertal children,and 20 pubertal adults was undertaken.Blood samples were obtained at 0,30,60,and 120 min after GnRH administration and the levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were measured.For each parameter,the sensitivities and specificities were estimated,and the receiver operating characteristic (ROC) curves were constructed.Results:The ROC curves indicated that a serum basal LH <0.6 IU/L or peak LH <9.74 IU/L resulted in moderate sensitivity (73.8% or 80.0%) and specificity (90.9% or 86.4%) in the diagnosis of HH in males.Serum basal LH <0.85 IU/L or basal FSH <2.43 IU/L resulted in moderate sensitivity (80.0% or 100.0%) and specificity (75.0% or 50.0%) in the diagnosis of HH in females.Conclusions:Our data suggest that isolated use of the gonadorelin stimulation test is almost sufficient to discriminate between HH and CDP in males,but unnecessary in females.The most useful predictor is serum basal or peak LH to differentiate these two disorders in males,but serum basal LH or FSH in females.

  19. Fabricating a Shell-Core Delayed Release Tablet Using Dual FDM 3D Printing for Patient-Centred Therapy.

    Science.gov (United States)

    Okwuosa, Tochukwu C; Pereira, Beatriz C; Arafat, Basel; Cieszynska, Milena; Isreb, Abdullah; Alhnan, Mohamed A

    2017-02-01

    Individualizing gastric-resistant tablets is associated with major challenges for clinical staff in hospitals and healthcare centres. This work aims to fabricate gastric-resistant 3D printed tablets using dual FDM 3D printing. The gastric-resistant tablets were engineered by employing a range of shell-core designs using polyvinylpyrrolidone (PVP) and methacrylic acid co-polymer for core and shell structures respectively. Filaments for both core and shell were compounded using a twin-screw hot-melt extruder (HME). CAD software was utilized to design a capsule-shaped core with a complementary shell of increasing thicknesses (0.17, 0.35, 0.52, 0.70 or 0.87 mm). The physical form of the drug and its integrity following an FDM 3D printing were assessed using x-ray powder diffractometry (XRPD), thermal analysis and HPLC. A shell thickness ≥0.52 mm was deemed necessary in order to achieve sufficient core protection in the acid medium. The technology proved viable for incorporating different drug candidates; theophylline, budesonide and diclofenac sodium. XRPD indicated the presence of theophylline crystals whilst budesonide and diclofenac sodium remained amorphous in the PVP matrix of the filaments and 3D printed tablets. Fabricated tablets demonstrated gastric resistant properties and a pH responsive drug release pattern in both phosphate and bicarbonate buffers. Despite its relatively limited resolution, FDM 3D printing proved to be a suitable platform for a single-process fabrication of delayed release tablets. This work reveals the potential of dual FDM 3D printing as a unique platform for personalising delayed release tablets to suit an individual patient's needs.

  20. 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

  1. Delayed release pancrelipase for treatment of pancreatic exocrine insufficiency associated with chronic pancreatitis

    Directory of Open Access Journals (Sweden)

    Devi Mukkai Krishnamurty

    2009-07-01

    Full Text Available Devi Mukkai Krishnamurty,1 Atoosa Rabiee,2 Sanjay B Jagannath,1 Dana K Andersen2Johns Hopkins University School of Medicine; 1Department of Medicine; 2Department of Surgery, Johns Hopkins Hospital, Baltimore, MD, USA; 2Johns Hopkins University School of Medicine, Johns Hopkins Bayview Medical Center, Baltimore, MD, USAAbstract: Pancreatic enzyme supplements (PES are used in chronic pancreatitis (CP for correction of pancreatic exocrine insufficiency (PEI as well as pain and malnutrition. The use of porcine pancreatic enzymes for the correction of exocrine insufficiency is governed by the pathophysiology of the disease as well as pharmacologic properties of PES. Variability in bioequivalence of PES has been noted on in vitro and in vivo testing and has been attributed to the differences in enteric coating and the degree of micro-encapsulation. As a step towards standardizing pancreatic enzyme preparations, the Food and Drug Administration now requires the manufacturers of PES to obtain approval of marketed formulations by April 2010. In patients with treatment failure, apart from evaluating drug and dietary interactions and compliance, physicians should keep in mind that patients may benefit from switching to a different formulation. The choice of PES (enteric coated versus non-enteric coated and the need for acid suppression should be individualized. There is no current standard test for evaluating adequacy of therapy in CP patients and studies have shown that optimization of therapy based on symptoms may be inadequate. Goals of therapy based on overall patient presentation and specific laboratory tests rather than mere correction of steatorrhea are needed.Keywords: pancreatic exocrine insufficiency, chronic pancreatitis, pancreatic enzyme supplement

  2. Development of a CO2 releasing co-formulation 1 based on starch, Saccharomyces cerevisiae and Beauveria bassiana attractive towards western corn rootworm larvae

    Science.gov (United States)

    CO2 is known as an attractant for many soil-dwelling pests. To implement an attract-and-kill strategy for soil pest control, CO2 emitting formulations need to be developed. This work aimed at the development of a slow release bead system in order to bridge the gap between application and hatching of...

  3. 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

  4. 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.

  5. 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.

  6. Sublethal effect of pyriproxyfen released from a fumigant formulation on fecundity, fertility, and ovicidal action in Aedes aegypti (Diptera: Culicidae).

    Science.gov (United States)

    Harburguer, Laura; Zerba, Eduardo; Licastro, Susana

    2014-03-01

    Dengue and dengue hemorrhagic fever are mosquito-borne viral diseases that coincide with the distribution of Aedes aegypti (L.), the primary vector in the tropical and semitropical world. With no available vaccine, controlling the dengue vector is essential to prevent epidemics. The effects of the insect growth regulator pyriproxyfen on Ae. aegypti adults that survived a treatment with a sublethal dose were investigated in the laboratory, including effects on their reproductive potential. Pyriproxyfen was released from a fumigant formulation at a dose causing 20 or 40% emergence inhibition (%EI). Females were dissected before and after blood feeding and the basal follicle number was counted. There were no differences between the control and treated group on the basal follicle number for both doses used. Fertility and fecundity were reduced at a concentration of EI40 but no at EI20. There was no ovicidal effect of pyriproxyfen by immersion of eggs in treated water neither when the females laid their eggs on a pyriproxyfen-treated surface. This work shows that sublethal doses of pyriproxyfen can have effects on fertility and fecundity ofAe. aegypti females, which together with its larvicidal activity could contribute to an overall decrease in a given population.

  7. Eco-friendly PEG-based controlled release nano-formulations of Mancozeb: Synthesis and bioefficacy evaluation against phytopathogenic fungi Alternaria solani and Sclerotium rolfsii.

    Science.gov (United States)

    Majumder, Sujan; Shakil, Najam A; Kumar, Jitendra; Banerjee, Tirthankar; Sinha, Parimal; Singh, Braj B; Garg, Parul

    2016-12-01

    Controlled release (CR) nano-formulations of Mancozeb (manganese-zinc double salt of N,N-bisdithiocarbamic acid), a protective fungicide, have been prepared using laboratory-synthesized poly(ethylene glycols) (PEGs)-based functionalized amphiphilic copolymers without using any surfactants or external additives. The release kinetics of the developed Mancozeb CR formulations were studied and compared with that of commercially available 42% suspension concentrate and 75% wettable powder. Maximum amount of Mancozeb was released on 42nd day for PEG-600 and octyl chain, PEG-1000 and octyl chain, and PEG-600 and hexadecyl chain, on 35th day for PEG-1000 and hexadecyl chain, on 28th day for PEG-1500 and octyl chain, PEG-2000 and octyl chain, PEG-1500 and hexadecyl chain, and PEG-2000 and hexadecyl chain in comparison to both commercial formulations (15th day). The diffusion exponent (n value) of Mancozeb in water ranged from 0.42 to 0.62 in tested formulations. The half-release (t1/2) values ranged from 17.35 to 35.14 days, and the period of optimum availability of Mancozeb ranged from 18.54 to 35.42 days. Further, the in vitro bioefficacy evaluation of developed formulations was done against plant pathogenic fungi Alternaria solani and Sclerotium rolfsii by poison food technique. Effective dose for 50% inhibition in mgL(-1) (ED50) values of developed formulations varied from 1.31 to 2.79 mg L(-1) for A. solani, and 1.60 to 3.14 mg L(-1) for S. rolfsii. The present methodology is simple, economical, and eco-friendly for the development of environment-friendly CR formulations of Mancozeb. These formulations can be used to optimize the release of Mancozeb to achieve disease control for the desired period depending upon the matrix of the polymer used. Importantly, the maximum amount of active ingredient remains available for a reasonable period after application. In addition, the developed CR formulations were found to be suitable for fungicidal applications, allowing use

  8. Formulation of a modified release metformin. HCl matrix tablet: influence of some hydrophilic polymers on release rate and in-vitro evaluation

    Directory of Open Access Journals (Sweden)

    John Rojas

    2011-09-01

    Full Text Available Metformin hydrochloride is an antidiabetic agent which improves glucose tolerance in patients with type 2 diabetes and reduces basal plasma levels of glucose. In this study, a simplex centroid experimental design with 69 runs was used to select the best combination of some hydrophilic polymers that rendered a 24 h in-vitro release profile of metformin.HCl. The Korsmeyer-Peppas model was used to model the dissolution profiles since it presented the best fit to the experimental data. Further, a cubic model predicted the best formulation of metformin.HCl containing polyvinyl pyrrolidone, ethyl cellulose, hydroxypropyl methyl cellulose, carrageenan, sodium alginate, and gum arabic at 6.26, 68.7, 6.26, 6.26, 6.26 and 6.26 % levels, respectively. The validation runs confirmed the accuracy of the cubic model with six components for predicting the best set of components which rendered a once-a-day modified release hydrophilic matrix tablet in compliance with the USP specifications.O cloridrato de metformina é um agente antidiabético que melhora a tolerância à glicose em pacientes com diabetes tipo 2 e reduz os níveis plasmáticos basais de glicose. Neste estudo, um projeto experimental do tipo "centróide simplex" com 69 tomadas foi usado para selecionar a melhor combinação de alguns polímeros hidrofílicos que gerou um perfil de liberação da metformina.HCl de 24 horas. O modelo Korsmeyer-Peppas foi usado para modelar os perfis de dissolução, uma vez que apresentou os melhores ajustes aos dados experimentais. Além disso, um modelo cúbico previu a melhor formulação de metformina.HCl sendo aquela contendo polivinilpirrolidona, etilcelulose, hidroxipropilmetil celulose, carragena, alginato de sódio e goma arábica nos níveis 6.26, 68.7, 6.26, 6.26, 6.26 e 6.26 %, respectivamente. As corridas de validação confirmaram a precisão do modelo cúbico com os seis componentes para prever o melhor conjunto de componentes que originou uma

  9. Preliminary Formulation of Finite Element Solution for the 1-D, 1-G Time Dependent Neutron Diffusion Equation without Consideration about Delay Neutron

    Energy Technology Data Exchange (ETDEWEB)

    Ryu, Eun Hyun; Song, Yong Mann; Park, Joo Hwan [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2013-05-15

    If time-dependent equation is solved with the FEM, the limitation of the input geometry will disappear. It has often been pointed out that the numerical methods implemented in the RFSP code are not state-of-the-art. Although an acceleration method such as the Coarse Mesh Finite Difference (CMFD) for Finite Difference Method (FDM) does not exist for the FEM, one should keep in mind that the number of time steps for the transient simulation is not large. The rigorous formulation in this study will richen the theoretical basis of the FEM and lead to an extension of the dynamics code to deal with a more complicated problem. In this study, the formulation for the 1-D, 1-G Time Dependent Neutron Diffusion Equation (TDNDE) without consideration of the delay neutron will first be done. A problem including one multiplying medium will be solved. Also several conclusions from a comparison between the numerical and analytic solutions, a comparison between solutions with various element orders, and a comparison between solutions with different time differencing will be made to be certain about the formulation and FEM solution. By investigating various cases with different values of albedo, theta, and the order of elements, it can be concluded that the finite element solution is agree well with the analytic solution. The higher the element order used, the higher the accuracy improvements are obtained.

  10. Winter warming delays dormancy release, advances budburst, alters carbohydrate metabolism and reduces yield in a temperate shrub

    DEFF Research Database (Denmark)

    Pagter, Majken; Andersen, Uffe Brandt; Andersen, Lillie

    2015-01-01

    winter warming modifies phenological traits in a woody perennial known to have a large chilling requirement and to be sensitive to spring frost. Warming delayed dormancy release more in the cultivar ‘Narve Viking’ than in the cultivar ‘Titania’, but advanced budburst and flowering predominantly...... in ‘Titania’. Since ‘Narve Viking’ has a higher chilling requirement than ‘Titania’, this indicates that, in high-chillingrequiring genotypes, dormancy responses may temper the effect of warming on spring phenology. Winter Warming significantly reduced fruit yield the following summer in both cultivars...... at elevated temperature showed decreased levels of sucrose in stems of both cultivars and flower buds of ‘Narve Viking’, which, in buds, was associated with increased concentrations of glucose and fructose. Hence, winter warming influences carbohydrate metabolism, but it remains to be elucidated whether...

  11. The role of lipid-based nano delivery systems on oral bioavailability enhancement of fenofibrate, a BCS II drug: comparison with fast-release formulations.

    Science.gov (United States)

    Weng, Tengfei; Qi, Jianping; Lu, Yi; Wang, Kai; Tian, Zhiqiang; Hu, Kaili; Yin, Zongning; Wu, Wei

    2014-09-24

    The aim of this study was to compare various formulations solid dispersion pellets (SDP), nanostructured lipid carriers (NLCs) and a self-microemulsifying drug delivery system (SMEDDS) generally accepted to be the most efficient drug delivery systems for BCS II drugs using fenofibrate (FNB) as a model drug. The size and morphology of NLCs and SMEDDS was characterized by dynamic light scattering (DLS) and transmission electron microscopy (TEM). Their release behaviors were investigated in medium with or without pancreatic lipase. The oral bioavailability of the various formulations was compared in beagle dogs using commercial Lipanthyl® capsules (micronized formulation) as a reference. The release of FNB from SDP was much faster than that from NLCs and SMEDDS in medium without lipase, whereas the release rate from NLCs and SMEDDS was increased after adding pancreatic lipase into the release medium. However, NLCs and SMEDDS increased the bioavailability of FNB to 705.11% and 809.10%, respectively, in comparison with Lipanthyl® capsules, although the relative bioavailability of FNB was only 366.05% after administration of SDPs. Thus, lipid-based drug delivery systems (such as NLCs and SMEDDS) may have more advantages than immediate release systems (such as SDPs and Lipanthyl® capsules).

  12. A combination of chondroitinase ABC, glial cell line-derived neurotrophic factor, and Nogo A antibody delayed-release microspheres for the treatment of spinal cord injury

    Institute of Scientific and Technical Information of China (English)

    Yu Zhang; Yueming Song

    2011-01-01

    The purpose of this study was to evaluate the effect of poly(lactide-co-glycolic acid) delayed-release microspheres, which were prepared using glial cell line-derived neurotrophic factor (GDNF), on the delayed-release, controllability, and protection of GDNF activity. The present study is the first to combine chondroitinase ABC, GDNF, and Nogo A antibody delayed-release microspheres for the treatment of spinal cord injury. Results show that the combined therapy of chondroitinase ABC,GDNF, and Nogo A antibody microspheres can increase the immunoreaction of neurofilament 200in the injured spinal cord, and this therapeutic effect was better than chondroitinase ABC, GDNF, or Nogo A antibody microspheres administered singularly.

  13. Liver targeting and the delayed drug release of the nanoparticles of adriamycin polybutylcyanoacrylate in mice

    Institute of Scientific and Technical Information of China (English)

    SHEN Liang-fang; ZHANG Yang-de; SHEN Hai-ju; ZENG Shan; WANG Xin; WANG Cheng; LE Yuan; SHEN Hong

    2006-01-01

    Background Liver targeting drug delivery systems can improve the curative effects and relieve the cytotoxicityof the chemotherapy drugs in the treatment of liver diseases. Nanoparticles carrying therapeutic drugs arecurrently under hot investigation with great clinical significance. This study was aimed to investigate thedifferent tissue distribution of the adriamycin polybutylcyanoacrylate nanoparticle (ADM-PBCA-NP) in the micebody after an injection via lateral tail vein, and to study the liver targeting effects of ADM-PBCA-NP in differentdiameters on normal mice liver.Methods One hundred and eighty Kunming mice were randomly divided into 6 groups with 30 mice in eachgroup (5 treatment groups of ADM-PBCA-NP in the different diameter ranges, non-conjugated free adriamycininjection was employed as the control group). A single dose of either conjugated or free adriamycin equaled2 mg/kg of body weight was delivered via the tail vein. Five mice in each trail were sacrificed at 5, 15, 30minutes, 1, 5 and 12 hours postinjection, respectively. The adriamycin concentrations in the respectivelycollected liver, kidney, spleen, heart, lung and plasma were demonstrated using a high performance liquidchromatography with fluorescence detector.Results Compared with the control group, adriamycin was hardly detected in the heart muscle of the treatmentgroups (P<0.05). The nanoparticle-conjugated adriamycin was cleaned up quickly from the kidney tissue. Theadriamycin concentrations of the mice liver and spleen in the experimental groups were significantly higher thanthat in the control group, except for the group with the nanoparticles diameters of (22.3±6.2) nm (P<0.05). TheADM-PBCA-NP in (101.0±20.3) nm diameter had the highest liver distribution, and the second highestadriamycin distribution in liver was the group of (143.0±23.5) nm diameter (P<0.05). Moreover, adriamycinwas released slowly in the liver during the detection period in the experimental groups. ADM

  14. The Physicochemical Evaluation and Applicability of Landolphia owariensis latex as a Release Modulating Agent in its Admixture with Carbosil® in Ibuprofen-loaded Self-Emulsifying Oil Formulations

    Directory of Open Access Journals (Sweden)

    N C Obitte

    2009-12-01

    Full Text Available Summary: The need to address the problematic gastric irritation side effects and inconsistent bioavailability of most poorly soluble drugs has drawn the attention of researchers to self emulsifying drug delivery system as one of the possible solutions to these problems. Secondly self emulsifying oil formulations good as they may be could be associated with leakage from their hard gelatin capsules. This further motivated the introduction of gelling agents to address this problem. The objective of this work was to investigate some preliminary properties of Landolphia owariensis latex, including its applicability as a release modulating agent when admixed with Carbosil®, a gelling agent in Ibuprofen-loaded Palm Kernel oil (PKO-based self-emulsifying oil formulations (SEOFs. Purification and precipitation were carried out on the oil and the latex respectively. Some physicochemical properties of the latex were also determined. SEOFs were formulated using varying concentrations of PKO, Tween 80 and Span 85 and thereafter tested for isotropicity. Drug-loaded SEOFs with or without Landolphia owariensis latex (LOL and Carbosil-LOL admixture respectively were evaluated for stability, emulsification time, drug release, aqueous dilution, freeze thaw and drug precipitation tests. Results showed that LOL contained some phytocostituents, had a reasonable adhesive strength, and could retard aqueous permeation. Three out of nine batches of the SEOFs passed the isotropicity test, witnessed no phase separation when emulsified and diluted, and could resist drug precipitation after dilution. LOL did not at all delay drug release from SEOFs unlike LOL-Carbosil admixture. LOL-Carbosil admixture significantly (p<0.05 reduced emulsification time. There was no consistent trend in the dynamic viscosity result. Stability of the SEOFs was maintained at refrigeration temperature of 20C. The above results indicated that LOL, an oil-soluble latex possesses excipient

  15. A randomized, crossover pharmacodynamic study of immediate-release omeprazole/sodium bicarbonate and delayed-release lansoprazole in healthy adult volunteers.

    Science.gov (United States)

    Pratha, Vijayalakshmi S; McGraw, Thomas; Tobin, William

    2016-06-01

    Proton pump inhibitors (PPIs) effectively block gastric acid secretion and are the treatment of choice for heartburn. PPIs differ, however, in onset of action and bioavailability. In this single-center, open-label, three-way crossover study, onset of action of immediate-release omeprazole 20 mg/sodium bicarbonate 1100 mg (IR-OME) and delayed-release (DR) lansoprazole 15 mg was evaluated in 63 healthy fasting adults. Subjects were randomized to once daily IR-OME, or DR-lansoprazole, or no treatment for 7 days. The primary efficacy endpoint was the earliest time where a statistically significant difference was observed between IR-OME and DR-lansoprazole in median intragastric pH scores for three consecutive 5-min intervals on day 7. Secondary endpoints compared effects of active treatments on days 1 and 7 (e.g., time to sustained inhibition, percentage of time with pH >4). A significant difference in median intragastric pH favoring IR-OME was observed on day 7 starting at the 10- to 15-min interval postdosing (P = 0.024) and sustaining through the 115- to 120-min interval (P = 0.017). On day 1, IR-OME achieved sustained inhibition of intragastric acidity significantly faster than DR-lansoprazole. IR-OME maintained pH >4 significantly longer than DR-lansoprazole over a 24-h period (P = 0.007) on day 7. Overall, results of this study demonstrate IR-OME is safe and well tolerated and that treatment with IR-OME results in significantly faster onset of action and better gastric acid suppression at steady state than DR-lansoprazole.

  16. Assessment of pharmacokinetics and pharmacodynamic effects related to abuse potential of a unique oral osmotic-controlled extended-release methylphenidate formulation in humans.

    Science.gov (United States)

    Parasrampuria, Dolly A; Schoedel, Kerri A; Schuller, Reinhard; Gu, Joan; Ciccone, Patrick; Silber, Steven A; Sellers, Edward M

    2007-12-01

    This was a double-blind, placebo-controlled, randomized, 5-period crossover study in 49 healthy subjects with a history of light (occasional) recreational stimulant use, to evaluate the abuse-related subjective effects of oral osmotic-controlled extended-release methylphenidate with comparable doses of immediate-release methylphenidate. Healthy subjects with a history of light recreational stimulant use were enrolled in the study if they demonstrated a positive response to a 20-mg dose of d-amphetamine and a negative placebo response. Enrolled subjects received single doses of placebo, 54 and 108 mg osmotic-controlled extended-release methylphenidate, and 50 and 90 mg immediate-release methylphenidate. For each treatment, pharmacokinetics, pharmacodynamics, and safety were assessed for 24 hours. Subjective data were collected through standard questionnaires and visual analog scales for positive, stimulant, negative, and other effects. Immediate-release and osmotic-controlled extended-release methylphenidate produced expected plasma concentration-time profiles of d-methylphenidate. Both doses of immediate-release methylphenidate (50 and 90 mg) produced statistically significantly higher subjective effects (eg, positive, stimulant) with respect to placebo for all measures. The higher osmotic-controlled extended-release methylphenidate dose of 108 mg also produced statistically significant differences from placebo for most measures. However, the most commonly prescribed therapeutic dose of osmotic-controlled extended-release methylphenidate (54 mg) did not produce significant differences from placebo for most measures. In addition, for comparable dose levels, osmotic-controlled extended-release methylphenidate produced lower positive and stimulant subjective effects than immediate-release methylphenidate, and low-dose immediate-release methylphenidate (50 mg) produced greater subjective effects than high-dose osmotic-controlled extended-release methylphenidate, with

  17. THE STUDY ON THE EFFECT OF FORMULATION VARIABLES ON IN VITRO FLOATING TIME AND THE RELEASE PROPERTIES OF A FLOATING DRUG DELIVERY SYSTEM BY A STATISTICAL OPTIMIZATION TECHNIQUE

    Directory of Open Access Journals (Sweden)

    C. NARENDRA

    2008-03-01

    Full Text Available The present investigation concerns the evaluation of the effect of formulation variables on in vitro floating time and the release properties in developing a floating drug delivery system (FDDS containing a highly water soluble drug metoprolol tartrate (MT in the presence of a gas generating agent. A 32 full factorial design was employed in formulating the FDDS containing hydroxyl propylmethylcellulose (HPMC K4M and sodium carboxymethylcellulose (NaCMC as swellable polymers. Drug-to-polymer ratio and polymer-to-polymer ratio were included as independent variables. The main effect and the interaction terms were quantitatively evaluated by a quadratic model to predict formulations with the floating time desired, and the release properties. It was found that only drug-to-polymer ratio and its quadratic term were found to be significantly affective for all the response variables. Non-Fickian transport was confirmed as a release mechanism from the optimized formulations. The desirability function was used to optimize the response variables, each having a different target, and the observed responses were highly agreed with experimental values. The results demonstrate the feasibility of the model in the development of FDDS containing a highly water-soluble drug MT.

  18. Influence of Molecular Weight of Carriers and Processing Parameters on the Extrudability, Drug Release, and Stability of Fenofibrate Formulations Processed by Hot-Melt Extrusion.

    Science.gov (United States)

    Alsulays, Bader B; Park, Jun-Bom; Alshehri, Sultan M; Morott, Joseph T; Alshahrani, Saad M; Tiwari, Roshan V; Alshetaili, Abdullah S; Majumdar, Soumyajit; Langley, Nigel; Kolter, Karl; Gryczke, Andreas; Repka, Michael A

    2015-10-01

    The objective of this study was to investigate the extrudability, drug release, and stability of fenofibrate (FF) formulations utilizing various hot-melt extrusion processing parameters and polyvinylpyrrolidone (PVP) polymers of various molecular weights. The different PVP grades selected for this study were Kollidon(®) 12 PF (K12), Kollidon(®) 30 (K30), and Kollidon(®) 90 F (K90). FF was extruded with these polymers at three drug loadings (15%, 25%, and 35% w/w). Additionally, for FF combined with each of the successfully extruded PVP grades (K12 and K30), the effects of two levels of processing parameters for screw design, screw speed, and barrel temperature were assessed. It was found that the FF with (K90) was not extrudable up to 35% drug loading. With low drug loading, the polymer viscosity significantly influenced the release of FF. The crystallinity remaining was vital in the highest drug-loaded formulation dissolution profile, and the glass transition temperature of the polymer significantly affected its stability. Modifying the screw configuration resulted in more than 95% post-extrusion drug content of the FF-K30 formulations. In contrast to FF-K30 formulations, FF release and stability with K12 were significantly influenced by the extrusion temperature and screw speed.

  19. Review of levetiracetam, with a focus on the extended release formulation, as adjuvant therapy in controlling partial-onset seizures

    Directory of Open Access Journals (Sweden)

    Carol M Ulloa

    2009-09-01

    Full Text Available Carol M Ulloa, Allen Towfigh, Joseph SafdiehDepartment of Neurology and Neuroscience, Weill Medical College of Cornell University, New York, NY, USAAbstract: Levetiracetam is a second-generation antiepileptic drug (AED with a unique chemical structure and mechanism of action. The extended release formulation of levetiracetam (Keppra XR™; UCB Pharma was recently approved by the Food and Drug Administration for adjunctive therapy in the treatment of partial-onset seizures in patients 16 years of age and older with epilepsy. This approval is based on a double-blind, randomized, placebo-controlled, multicenter, multinational trial. Levetiracetam XR allows for once-daily dosing, which may increase compliance and, given the relatively constant plasma concentrations, may minimize concentration-related adverse effects. Levetiracetam’s mode of action is not fully elucidated, but it has been found to target high-voltage, N-type calcium channels as well as the synaptic vesicle protein 2A (SV2A. Levetiracetam has nearly ideal pharmacokinetics. It is rapidly and almost completely absorbed after oral ingestion, is ‹10% protein-bound, demonstrates linear kinetics, is minimally metabolized through a pathway independent of the cytochrome P450 system, has no significant drug–drug interactions, and has a wide therapeutic index. The most common reported adverse events with levetiracetam XR were somnolence, irritability, dizziness, nausea, influenza, and nasopharyngitis. Levetiracetam XR provides an efficacious and well-tolerated treatment option for adjunctive therapy in the treatment of partial-onset seizures.Keywords: levetiracetam, partial-onset seizures, antiepileptic drugs

  20. Efficacy and tolerability of a prolonged release ferrous sulphate formulation in iron deficiency anaemia: a non-inferiority controlled trial.

    Science.gov (United States)

    Zaim, Mohammed; Piselli, Leonardo; Fioravanti, Pino; Kanony-Truc, Claire

    2012-03-01

    Iron deficiency anaemia (IDA) is the last stage of iron deficiency, consecutive to an imbalance between iron supply through food intake and iron loss through physiological or pathological processes. As well as by haemoglobin levels, IDA is diagnosed by measuring biomarkers of iron stores. Women are most affected by IDA since their teenage years, as menstruation constitutes a chronic iron loss. Oral supplementation with ferrous sulphate is an effective therapy, but gastrointestinal side effects may impair treatment compliance. The present multicentric randomised controlled trial was designed to assess the non-inferiority of a ferrous sulphate prolonged release formulation called V0355 with the referential ferrous sulphate Ferrograd® in a population of Italian women aged 18-50 years diagnosed for IDA. Three hundred and ninety-nine patients were randomised to receive V0355 (80 mg Fe/day) or Ferrograd® (105 mg Fe/day). After 12 weeks of treatment, the difference in the mean haemoglobin level between the two groups was 0.081 g/dL ([-2.986;1.361], p = 0.54), which confirmed the hypothesis of non-inferiority. All the other biochemical parameters (serum iron, serum ferritin, transferrin, and soluble transferrin receptor) and haematological parameters (erythrocytes count, reticulocytes count, haematocrit, and mean corpuscular volume), as well as patient's anaemia-related symptoms, were not different between treatment groups throughout the study. Furthermore, the incidence of gastrointestinal adverse events of moderate and severe intensity was significantly lower (p = 0.007) in the V0355 group (5.6%) than in the Ferrograd® group (13.9%). V0355 was as efficient as Ferrograd® in the treatment of anaemia and exhibited a better gastrointestinal tolerance profile.

  1. Monitoring the hydrolyzation of aspirin during the dissolution testing for aspirin delayed-release tablets with a fiber-optic dissolution system

    Institute of Scientific and Technical Information of China (English)

    Yan Wang; Ping-Ping Xu; Xin-Xia Li; Kun Nie; Ming-Fu Tuo; Bin Kong; Jian Chen

    2012-01-01

    The purpose of this study was to investigate the hydrolyzation of aspirin during the process of dissolution testing for aspirin delayed-release tablets. Hydrolysis product of salicylic acid can result in adverse effects and affect the determination of dissolution rate assaying. In this study, the technique of differential spectra was employed, which made it possible to monitor the dissolution testing in situ. The results showed that the hydrolyzation of aspirin made the percentage of salicylic acid exceed the limit of free salicylic acid (4.0), and the hydrolyzation may affect the quality detection of aspirin delayed-release tablets.

  2. Adsorption-desorption behavior of 2,4-D on NCP-modified bentonite and zeolite: implications for slow-release herbicide formulations.

    Science.gov (United States)

    Bakhtiary, Somayeh; Shirvani, Mehran; Shariatmadari, Hossein

    2013-01-01

    Clay minerals have obtained considerable attention for slow-release formulation of herbicides to increase weed control efficacy and reduce leaching potential and environmental pollution. This study deals with preparing, characterizing and examining the potentials of modified bentonite and zeoilite in adsorption and release of 2,4-dichlorophenoxyacetic acid (2,4-D) herbicide. 2,4-D sorption of the N-cetylpyridinium (NCP)-modified bentonites and zeolites were much higher than those of unmodified substrates. The 2,4-D adsorption capacity of the organo-minerals increased with increasing surfactant loading. Desorption isotherms of 2,4-D did not coincide their corresponding sorption isotherms showing hysteresis. The proportion of 2,4-D released from the organo-minerals after seven desorption cycles varied between 29% and 50% of the total retained herbicide. The sorbed 2,4-D on the adsorbents showed gradual release pattern with time. The release pattern of 2,4-D from NCP-modified bentonite and zeolite, make these synthetic organo-minerals suitable candidate for slow release formulation of 2,4-D.

  3. Oral pulsatile delivery: rationale and chronopharmaceutical formulations.

    Science.gov (United States)

    Maroni, Alessandra; Zema, Lucia; Del Curto, Maria Dorly; Loreti, Giulia; Gazzaniga, Andrea

    2010-10-15

    Oral pulsatile/delayed delivery systems are designed to elicit programmable lag phases preceding a prompt and quantitative, repeated or prolonged release of drugs. Accordingly, they draw increasing interest because of the inherent suitability for accomplishing chronotherapeutic goals, which have recently been highlighted in connection with a number of widespread chronic diseases with typical night or early-morning recurrence of symptoms (e.g. bronchial asthma, cardiovascular disease, rheumatoid arthritis, early-morning awakening). In addition, time-based colonic release can be attained when pulsatile delivery systems are properly adapted to overcome unpredictable gastric emptying and provide delay phases that would approximately match the small intestinal transit time. Oral pulsatile delivery is pursued by means of a variety of release platforms, namely reservoir, capsular and osmotic devices. The aim of the present review is to outline the rationale and main formulation strategies behind delayed-release dosage forms intended for the pharmacological treatment of chronopathologies.

  4. Development of in vitro-in vivo correlation for extended-release niacin after administration of hypromellose-based matrix formulations to healthy volunteers.

    Science.gov (United States)

    Kesisoglou, Filippos; Rossenu, Stefaan; Farrell, Colm; Van Den Heuvel, Michiel; Prohn, Marita; Fitzpatrick, Shaun; De Kam, Pieter-Jan; Vargo, Ryan

    2014-11-01

    Development of in vitro-in vivo correlations (IVIVCs) for extended-release (ER) products is commonly pursued during pharmaceutical development to increase product understanding, set release specifications, and support biowaivers. This manuscript details the development of Level C and Level A IVIVCs for ER formulations of niacin, a highly variable and extensively metabolized compound. Three ER formulations were screened in a cross-over study against immediate-release niacin. A Multiple Level C IVIVC was established for both niacin and its primary metabolite nicotinuric acid (NUA) as well as total niacin metabolites urinary excretion. For NUA, but not for niacin, Level A IVIVC models with acceptable prediction errors were achievable via a modified IVIVC rather than a traditional deconvolution/convolution approach. Hence, this is in contradiction with current regulatory guidelines that suggest that when a Multiple Level C IVIVC is established, Level A models should also be readily achievable. We demonstrate that for a highly variable, highly metabolized compound such as niacin, development of a Level A IVIVC model fully validated according to agency guidelines may be challenging. However, Multiple Level C models are achievable and could be used to guide release specifications and formulation/manufacturing changes.

  5. Influence of some formulation variables on the optimization of pH-dependent, colon-targeted, sustained-release mesalamine microspheres.

    Science.gov (United States)

    El-Bary, Ahmed Abd; Aboelwafa, Ahmed A; Al Sharabi, Ibrahim M

    2012-03-01

    The aim of this work was to understand the influence of different formulation variables on the optimization of pH-dependent, colon-targeted, sustained-release mesalamine microspheres prepared by O/O emulsion solvent evaporation method, employing pH-dependent Eudragit S and hydrophobic pH-independent ethylcellulose polymers. Formulation variables studied included concentration of Eudragit S in the internal phase and the ratios between; internal to external phase, drug to Eudragit S and Eudragit S to ethylcellulose to mesalamine. Prepared microspheres were evaluated by carrying out in vitro release studies and determination of particle size, production yield, and encapsulation efficiency. In addition, morphology of microspheres was examined using optical and scanning electron microscopy. Emulsion solvent evaporation method was found to be sensitive to the studied formulation variables. Particle size and encapsulation efficiency increased by increasing Eudragit S concentration in the internal phase, ratio of internal to external phase, and ratio of Eudragit S to the drug. Employing Eudragit S alone in preparation of the microspheres is only successful in forming acid-resistant microspheres with pulsatile release pattern at high pH. Eudragit S and ethylcellulose blend microspheres were able to control release under acidic condition and to extend drug release at high pH. The stability studies carried out at 40°C/75% RH for 6 months proved the stability of the optimized formulation. From the results of this investigation, microencapsulation of mesalamine in microspheres using blend of Eudragit S and ethylcellulose could constitute a promising approach for site-specific and controlled delivery of drug in colon.

  6. The influence of hydrophylic polymers on the release rate of calcium dobesilate in hydrogel formulation assessed in vitro using porcine ear skin

    Directory of Open Access Journals (Sweden)

    Wojcik-Pastuszka Dorota

    2015-12-01

    Full Text Available A shortage of available experimental data exists in the available bibliography on the release rate of calcium dobesilate (CD from hydrogel formulations. Thus, the aim of the study was to evaluate the effect of selected hydrophilic nonionic polymers and anionic polymers on the release rate of CD from formulation provided for dermal application, as compared to the reference product in the market. The work utilized excised pork skin, while, Methylcellulose (MC, hydroxypropyl methylcellulose (HPMC, and anionic polymers (copolymers of acrylic acid were used as CD carriers. The release study was executed by the pharmacopoeial paddle method, with extraction cells and fresh excised porcine skin as a membrane. CD in aqueous acceptor fluid was quantified by UV-VIS spectrometry at 300 nm. Subsequently, the kinetic curves were fitted to a zero-order kinetics model, a first-order kinetics model, a second-order kinetics model, as well as to the Higuchi model. The work saw that porcine ear skin influences the release pattern of the CD, compared to the artificial membrane. In the study, the evaluated formulations with MC, polyacrylic acid (PA and polyacrylate crosspolymer 11 (PC-11 deliver over 60% of the active component (AC, within 250 min, through the excised porcine ear skin, to the acceptor compartment. Moreover, the release observed via porcine ear skin to the aqueous acceptor compartment is congenial to zero-order or first-order kinetics. In addition, the formulations prepared on the basis of MC and PA appear to control AC delivery, independently of actual concentration of AC.

  7. Controlled-release of Bacillus thurigiensis formulations encapsulated in light-resistant colloidosomal microcapsules for the management of lepidopteran pests of Brassica crops

    Science.gov (United States)

    Bashir, Oumar; Lemoyne, Pierre

    2016-01-01

    Bacillus thuringiensis (B. t.) based formulations have been widely used to control lepidopteran pests in agriculture and forestry. One of their weaknesses is their short residual activity when sprayed in the field. Using Pickering emulsions, mixtures of spores and crystals from three B. t. serovars were successfully encapsulated in colloïdosomal microparticles (50 μm) using innocuous chemicals (acrylic particles, sunflower oil, iron oxide nanoparticles, ethanol and water). A pH trigger mechanism was incorporated within the particles so that B. t. release occurred only at pH > 8.5 which corresponds to the midgut pH of the target pests. Laboratory assays performed on Trichoplusia ni (T. ni) larvae demonstrated that the microencapsulation process did not impair B. t. bioactivity. The best formulations were field-tested on three key lepidopteran pests that attack Brassica crops, i.e., the imported cabbageworm, the cabbage looper and the diamondback moth. After 12 days, the mean number of larvae was significantly lower in microencapsulated formulations than in a commercial B. t. formulation, and the effect of microencapsulated formulations was comparable to a chemical pesticide (lambda-cyhalothrin). Therefore, colloïdosomal microcapsule formulations successfully extend the bioactivity of B. t. for the management of lepidopteran pests of Brassica crops. PMID:27761325

  8. Controlled-release of Bacillus thurigiensis formulations encapsulated in light-resistant colloidosomal microcapsules for the management of lepidopteran pests of Brassica crops

    Directory of Open Access Journals (Sweden)

    Oumar Bashir

    2016-10-01

    Full Text Available Bacillus thuringiensis (B. t. based formulations have been widely used to control lepidopteran pests in agriculture and forestry. One of their weaknesses is their short residual activity when sprayed in the field. Using Pickering emulsions, mixtures of spores and crystals from three B. t. serovars were successfully encapsulated in colloïdosomal microparticles (50 μm using innocuous chemicals (acrylic particles, sunflower oil, iron oxide nanoparticles, ethanol and water. A pH trigger mechanism was incorporated within the particles so that B. t. release occurred only at pH > 8.5 which corresponds to the midgut pH of the target pests. Laboratory assays performed on Trichoplusia ni (T. ni larvae demonstrated that the microencapsulation process did not impair B. t. bioactivity. The best formulations were field-tested on three key lepidopteran pests that attack Brassica crops, i.e., the imported cabbageworm, the cabbage looper and the diamondback moth. After 12 days, the mean number of larvae was significantly lower in microencapsulated formulations than in a commercial B. t. formulation, and the effect of microencapsulated formulations was comparable to a chemical pesticide (lambda-cyhalothrin. Therefore, colloïdosomal microcapsule formulations successfully extend the bioactivity of B. t. for the management of lepidopteran pests of Brassica crops.

  9. Acid Inhibitory Effect of a Combination of Omeprazole and Sodium Bicarbonate (CDFR0209) Compared With Delayed-Release Omeprazole 40 mg Alone in Healthy Adult Male Subjects.

    Science.gov (United States)

    Kim, Kyu-Nam; Yang, Sung-Won; Kim, Hyunil; Kwak, Seong Shin; Kim, Young-Sang; Cho, Doo-Yeoun

    2017-01-23

    CDFR0209, a combination of an immediate-release formulation of omeprazole 40 mg and sodium bicarbonate 1100 mg, has been developed to treat acid-related disorders. We compared the acid inhibitory effects of CDFR0209 and delayed-release omeprazole (omeprazole-DR, Losec 40 mg) after repeated dosing in Helicobacter pylori-negative healthy adult male subjects. In this 2-period crossover study, 30 subjects were randomized to CDFR0209 or omeprazole-DR daily for 7 days. An ambulatory continuous 24-hour intragastric pH recording was performed at baseline and on days 1 and 7 of each administration period. Integrated gastric acidity was calculated from time-weighted average hydrogen ion concentrations at each hour of the 24-hour record. An analysis of variance model was used to test the pharmacodynamic equivalence of CDFR0209 and omeprazole-DR, using the natural logarithmic transformation of the percent decrease from baseline in integrated gastric acidity for the 24-hour interval after the seventh dose of each omeprazole formulation. The geometric least-squares mean ratios (CDFR0209/omeprazole-DR) of the percent decrease from baseline in integrated gastric acidity was 0.98 (90%CI, 0.93-1.07). Both CDFR0209 and omeprazole-DR are equally effective in decreasing integrated gastric acidity at steady state.

  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. Bioequivalence of two lansoprazole delayed release capsules 30 mg in healthy male volunteers under fasting, fed and fasting-applesauce conditions: a partial replicate crossover study design to estimate the pharmacokinetics of highly variable drugs.

    Science.gov (United States)

    Thota, S; Khan, S M; Tippabhotla, S K; Battula, R; Gadiko, C; Vobalaboina, V

    2013-11-01

    An open-label, 2-treatment, 3-sequence, 3-period, single-dose, partial replicate crossover studies under fasting (n=48), fed (n=60) and fasting-applesauce (n=48) (sprinkled on one table spoonful of applesauce) modalities were conducted in healthy adult male volunteers to evaluate bioequivalence between 2 formulations of lansoprazole delayed release capsules 30 mg. In all the 3 studies, as per randomization, either test or reference formulations were administered in a crossover manner with a required washout period of at least 7 days. Blood samples were collected adequately (0-24 h) to determine lansoprazole plasma concentrations using a validated LC-MS/MS analytical method. To characterize the pharmacokinetic parameters (Cmax, AUC0-t, AUC0-∞, Tmax, Kel and T1/2) of lansoprazole, non-compartmental analysis and ANOVA was applied on ln-transformed values. The bioequivalence was tested based on within-subject variability of the reference formulation. In fasting and fed studies (within-subject variability>30%) bioequivalence was evaluated with scaled average bioequivalence, hence for the pharmacokinetic parameters Cmax, AUC0-t and AUC0-∞, the 95% upper confidence bound for (μT-μR)2-θσ2 WR was ≤0, and the point estimates (test-to-reference ratio) were within the regulatory acceptance limit 80.00-125.00%. In fasting-applesauce study (within-subject variability<30%) bioequivalence was evaluated with average bioequivalence, the 90% CI of ln-transformed data of Cmax, AUC0-t and AUC0-∞ were within the regulatory acceptance limit 80.00-125.00%. Based on these aforesaid statistical inferences, it was concluded that the test formulation is bioequivalent to reference formulation.

  12. Formulation design and evaluation of Cefuroxime axetil 125 mg immediate release tablets using different concentration of sodium lauryl sulphate as solubility enhancer

    Directory of Open Access Journals (Sweden)

    Fozia Israr

    2014-12-01

    Full Text Available Cefuroxime axetil immediate release tablets were formulated by direct compression method with different percentages of sodium lauryl sulphate (SLS such as 0.5, 1.0, 1.5 and also without SLS. Resulting batches of tablets were evaluated by both pharmacopeial and non-pharmacopeial methods to ascertain the physico-mechanical properties. Dissolution test were carried out in different medium like 0.07 M HCl, distilled water, 0.1M HCl of pH 1.2 and phosphate buffers at pH 4.5 and 6.8 to observe the drug release against the respective concentration of SLS used. Later, test formulations were compared by f1(dissimilarity and f2(similarity factors using a reference brand of cefuroxime axetil. Significant differences (p<0.05 in dissolution rate were recorded with the change in concentration of SLS in different media. Test formulation T3 containing 1% SLS was found to be best optimized formulation based on assay, disintegration, dissolution and similarity and dissimilarity factors.

  13. Development and validation of stability indicating method for the quantitative determination of venlafaxine hydrochloride in extended release formulation using high performance liquid chromatography

    Directory of Open Access Journals (Sweden)

    Jaspreet Kaur

    2010-01-01

    Full Text Available Objective : Venlafaxine,hydrochloride is a structurally novel phenethyl bicyclic antidepressant, and is usually categorized as a serotonin-norepinephrine reuptake inhibitor (SNRI but it has been referred to as a serotonin-norepinephrine-dopamine reuptake inhibitor. It inhibits the reuptake of dopamine. Venlafaxine HCL is widely prescribed in the form of sustained release formulations. In the current article we are reporting the development and validation of a fast and simple stability indicating, isocratic high performance liquid chromatographic (HPLC method for the determination of venlafaxine hydrochloride in sustained release formulations. Materials and Methods : The quantitative determination of venlafaxine hydrochloride was performed on a Kromasil C18 analytical column (250 x 4.6 mm i.d., 5 μm particle size with 0.01 M phosphate buffer (pH 4.5: methanol (40: 60 as a mobile phase, at a flow rate of 1.0 ml/min. For HPLC methods, UV detection was made at 225 nm. Results : During method validation, parameters such as precision, linearity, accuracy, stability, limit of quantification and detection and specificity were evaluated, which remained within acceptable limits. Conclusions : The method has been successfully applied for the quantification and dissolution profiling of Venlafaxine HCL in sustained release formulation. The method presents a simple and reliable solution for the routine quantitative analysis of Venlafaxine HCL.

  14. Extended release promethazine HCl using acrylic polymers by freeze-drying and spray-drying techniques: formulation considerations

    Directory of Open Access Journals (Sweden)

    Ruchi Tiwari

    2009-12-01

    Full Text Available The present study investigated a novel extended release system of promethazine hydrochloride (PHC with acrylic polymers Eudragit RL100 and Eudragit S100 in different weight ratios (1:1 and 1: 5, and in combination (0.5+1.5, using freeze-drying and spray-drying techniques. Solid dispersions were characterized by Fourier-transformed infrared spectroscopy (FT-IR, differential scanning calorimetry (DSC, Powder X-ray diffractometry (PXRD, Nuclear magnetic resonance (NMR, Scanning electron microscopy (SEM, as well as solubility and in vitro dissolution studies in 0.1 N HCl (pH 1.2, double-distilled water and phosphate buffer (pH 7.4. Adsorption tests from drug solution to solid polymers were also performed. A selected solid dispersion system was developed into capsule dosage form and evaluated for in vitro dissolution studies. The progressive disappearance of drug peaks in thermotropic profiles of spray-dried dispersions were related to increasing amount of polymers, while SEM studies suggested homogenous dispersion of drug in polymer. Eudragit RL100 had a greater adsorptive capacity than Eudragit S100, and thus its combination in (0.5+1.5 for S100 and RL 100 exhibited a higher dissolution rate with 97.14% drug release for twelve hours. Among different formulations, capsules prepared by combination of acrylic polymers using spray-drying (1:0.5 + 1.5 displayed extended release of drug for twelve hours with 96.87% release followed by zero order kinetics (r²= 0.9986.O presente trabalho compreendeu estudo de um novo sistema de liberação prolongada de cloridrato de prometazina (PHC com polímeros acrílicos Eudragit RL100 e Eudragit S100 em diferentes proporções em massa (1:1 e 1:5 e em combinação (0,5+1,5, utilizando técnicas de liofilização e de secagem por aspersão As dispersões sólidas foram caracterizadas por espectrofotometria no infravermelho por transformada de Fourier (FT-IR, calorimetria diferencial de varredura (DSC, difratometria

  15. Population pharmacokinetic modelling of tramadol using inverse Gaussian function for the assessment of drug absorption from prolonged and immediate release formulations.

    Science.gov (United States)

    Brvar, Nina; Mateović-Rojnik, Tatjana; Grabnar, Iztok

    2014-10-01

    This study aimed to develop a population pharmacokinetic model for tramadol that combines different input rates with disposition characteristics. Data used for the analysis were pooled from two phase I bioavailability studies with immediate (IR) and prolonged release (PR) formulations in healthy volunteers. Tramadol plasma concentration-time data were described by an inverse Gaussian function to model the complete input process linked to a two-compartment disposition model with first-order elimination. Although polymorphic CYP2D6 appears to be a major enzyme involved in the metabolism of tramadol, application of a mixture model to test the assumption of two and three subpopulations did not reveal any improvement of the model. The final model estimated parameters with reasonable precision and was able to estimate the interindividual variability of all parameters except for the relative bioavailability of PR vs. IR formulation. Validity of the model was further tested using the nonparametric bootstrap approach. Finally, the model was applied to assess absorption kinetics of tramadol and predict steady-state pharmacokinetics following administration of both types of formulations. For both formulations, the final model yielded a stable estimate of the absorption time profiles. Steady-state simulation supports switching of patients from IR to PR formulation.

  16. Antibody Array-Generated Profiles of Cytokine Release from THP-1 Leukemic Monocytes Exposed to Different Amphotericin B Formulations

    OpenAIRE

    Turtinen, Lloyd W.; Prall, David N.; Bremer, Lindsay A.; Nauss, Rachel E.; Hartsel, Scott C.

    2004-01-01

    Cytokine antibody arrays were used to establish the profiles of cytokine release from THP-1 monocytes exposed to different amphotericin B (AMB) drug delivery systems. Fungizone (FZ) and Amphotec (ABCD) caused the release of significantly more inflammatory molecules and the release of inflammatory molecules at higher levels than either AmBisome (L-AMB) or Abelcet (ABLC) after 6 h of treatment. Specifically, tumor necrosis factor alpha (TNF-α), interleukin-8 (IL-8), GRO-(αβγ), monocyte chemoatt...

  17. Use of Placket-Burman statistical design to study effect of formulation variables on the release of drug from hot melt sustained release extrudates.

    Science.gov (United States)

    Jain, Satishkumar P; Singh, Pirthi Pal; Javeer, Sharad; Amin, Purnima D

    2010-06-01

    The present paper was focused on exploiting Plackett-Burman design to screen the effect of nine factors--poly (ethylene oxide) molecular weight (X(1)), poly (ethylene oxide) amount (X(2)), ethylcellulose amount (X(4)), drug solubility (X(5)), drug amount (X(6)), sodium chloride amount (X(7)), citric acid amount (X(8)), polyethylene glycol amount (X(9)), and glycerin amount (X(11)) on the release of drugs from the extended release extrudates, i.e., release rate and release mechanism. The experiments were carried out according to a nine-factor 12-run statistical model and subjected to an 8-h dissolution study in phosphate buffer pH 6.8. The significance of the model was indicated by the ANOVA and the residual analysis. Poly (ethylene oxide) amount, ethylcellulose amount and drug solubility had significant effect on the T90 values whereas poly (ethylene oxide) amount and ethylcellulose amount had significant effect on the n value.

  18. Bentonite and anthracite in alginate-based controlled release formulations to reduce leaching of chloridazon and metribuzin in a calcareous soil.

    Science.gov (United States)

    Flores Céspedes, F; Pérez García, S; Villafranca Sánchez, M; Fernández Pérez, M

    2013-08-01

    The leaching of herbicides through soil can be minimized using controlled release formulations (CRFs). In this research, bentonite and anthracite have been used as modifying agents in alginate-based CRFs prepared with chloridazon and metribuzin. These CRFs have been evaluated in a calcareous soil. The Kf and Koc values obtained from sorption experiments in soil have demonstrated a high leaching potential for both herbicides, mainly for metribuzin. Release kinetics in soil have showed that the control of release rate of chloridazon and metribuzin was possible by using bentonite and anthracite in CRFs, being this effect greater when we use anthracite as modifying sorbent. Using an empirical equation, the time taken for 50% of the active ingredient to be released (T50(soil)) was calculated. T50 values ranged between 2.88 d for metribuzin-bentonite alginate-based granules and 14.37 d for chloridazon-anthracite alginate-based granules, being the release rate higher in metribuzin CRFs than in those prepared with chloridazon, which has lower water solubility. Besides, a linear correlation between T50 values in water and soil was obtained. Mobility experiments carried out in a calcareous soil have shown that the use of CRFs reduces the presence of herbicides in the leachate compared to technical products, mainly for chloridazon. We found that one could design a right profile in the release rate of active ingredients from CRFs in each agro-environmental situation, and thus prevent the environmental pollution derived from the use of chloridazon and metribuzin.

  19. 1,25-Dihydroxyvitamin D3-glycoside of herbal origin exhibits delayed release pharmacokinetics when compared to its synthetic counterpart.

    Science.gov (United States)

    Bachmann, Heinrich; Offord-Cavin, Elizabeth; Phothirath, Phoukham; Horcajada, Marie-Noelle; Romeis, Peter; Mathis, Georg A

    2013-07-01

    Vitamin D requires two metabolic steps to become biologically active. In a first step 25-hydroxyvitamin D3 is formed, which acts as storage form. After a tightly controlled step in kidney the active metabolite 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) is formed. Because kidney is the relevant metabolic organ for this conversion, 1,25(OH)2D3 needs to be supplemented in patients with kidney malfunction or kidney failure. Synthetic 1,25(OH)2D3 (calcitriol) has been available as a drug for decades. Due to its high potency and its kinetic profile (fast absorption and rapid elimination) its therapeutic windows has proven to be relatively narrow. A natural form of the active metabolite was identified in a few plants, such as Solanum glaucophyllum (SG) and suggested as alternative for animal and human health. An extract of a SG variety bred for high and uniform level of glycosylated 1,25(OH)2D3 was chemically characterized. Among the typical pharmaceutically inactive plant components (carbohydrates 54.3%, protein 24.9%, minerals 17.1% and water 4.1%) high levels of 1,25(OH)2D3 and a unique flavonoid content was found (1.11mg total quercetin/g extract) consisting exclusively of the quercetin glycosides hyperoside, isoquercetin, rutin and apinosylrutin. The molecular distribution of glycosyl moieties in 1,25(OH)2D3 extracted from SG as determined by gel permeation chromatography was found to be 1-10 hexose units per aglycone. 1,25(OH)2D3-1-β-glucopyranoside was identified in the SG extract, while a di- and triglycoside have been identified in SG by other groups. The pharmacokinetic properties of synthetic 1,25(OH)2D3 and glycosylated 1,25(OH)2D3 extracted from SG were compared in male rats. When compared to synthetic 1,25(OH)2D3, SG-derived 1,25(OH)2D3 exhibited delayed absorption and elimination characteristics, resulting in delayed Tmax (6-12h vs. 1h) and increased T½ (approximately 30h vs. 23h). This putative modified release pattern may be attributed to the glycosylation

  20. Bioefficacy evaluation of controlled release formulations based on amphiphilic nano-polymer of carbofuran against Meloidogyne incognita infecting tomato.

    Science.gov (United States)

    Pankaj; Shakil, Najam Akhtar; Kumar, Jitendra; Singh, M K; Singh, Khajan

    2012-01-01

    In the present investigation, the bioefficacy of developed carbofuran formulations, with PEG-600 (7a, CP1) & PEG-900 (7b, CP2) @ 5, 10 and 20 ppm, along with commercial formulation of carbofuran 3G (CP0) were evaluated against the root-knot nematode, Meloidogyne incognita infecting tomato (cv. Pusa Ruby) in pot and field conditions. The bioefficacy data indicated that the formulations developed by utilizing polymers having PEG - 900 (7b) as hydrophilic segment were effective even at 14 days post inoculation (dpi) as evident from shoot and root length. Also, the reduction in penetration was found to be maximum with CP2 (3.6 - 4.6 J2s) at all concentrations compared to CP1 (6.6-16.4 J2s) and CP0 (29.3-32.6 J2s). Overall, CP2 was more effective in reducing the number of nematodes up to 14 days, compared to CP1 and CP0. Both the CR formulations (CP1 and CP2) in general significantly reduced the number of galls, when compared to CP0. However, under field conditions, lower concentrations (5, and 10 ppm) of CP2, were less effective in controlling the gall formation whereas, CP2 at 20 ppm, was most effective than other treatments. The study revealed that the developed CR formulations of carbofuran have the potential for effective management of M. incognita in tomato under field conditions.

  1. FORMULATION AND EVALUATION OF CONTROLLED POROSITY OSMOTIC TABLETS OF LORNOXICAM

    Directory of Open Access Journals (Sweden)

    A. Uma Maheswari*, K. Elango, Daisy Chellakumari, K. Saravanan and Anglina Jeniffer Samy

    2012-06-01

    Full Text Available The aim of the present study is to formulate and evaluate controlled release formulation of lornoxicam based on osmotic technology. Lornoxicam, a potent non-steroidal anti-inflammatory drug (NSAID with shorter half life, makes the development of sustained release (SR dosage forms extremely advantageous. However, due to its weak acidic nature, its release from SR delivery system is limited to the lower GIT which consequently leads to a delayed onset of its analgesic action. Basic pH modifier tromethamine and wicking agent SLS were incorporated into the core tablet to create basic environmental pH inside the tablets, which provide complete drug release that starts in the stomach to rapidly alleviate the painful symptoms and continue in the intestine to maintain protracted analgesic effect. The effect of different formulation variables namely level of osmogen (mannitol in the core tablet and level of pore former (sorbitol in the coating membrane on in-vitro release was studied. Lornoxicam release from controlled porosity osmotic pump was directly proportional to the pore former (sorbitol and level of osmogen (mannitol. Drug release from the developed formulations was independent of pH and agitational intensity and was dependent on osmotic pressure of the release media. Results of SEM studies showed the formation of pores in the membrane from where the drug release occurred. The optimized formulation was found to release the drug in zero order and found to be stable upon stability studies.

  2. Pharmacokinetic Studies in Healthy Subjects for the Development of an Extended-Release Tablet Formulation of Guaifenesin: A 505(b)(2) New Drug Application Approval.

    Science.gov (United States)

    Vilson, Lineau; Owen, Joel S

    2013-01-01

    Guaifenesin is an expectorant used to improve mucociliary clearance (MCC) and relieve chest congestion from upper respiratory tract infections. Immediate-release (IR) guaifenesin requires dosing every 4 hours to maintain efficacy because of the drug's short half-life. Extended-release (ER) guaifenesin has been developed to prolong efficacy and reduce dosing frequency. As part of the 505(b)(2) new drug application (NDA), the pharmacokinetics (PK) of an ER bi-layer tablet formulation of guaifenesin (Mucinex®) and bioequivalence to an over-the-counter (OTC) monograph IR formulation were evaluated in healthy subjects. In one study, subjects received 1,200 mg ER guaifenesin every 12 hours or 400 mg IR guaifenesin every 4 hours for 6 days. Steady-state exposures were equivalent between the two products, as demonstrated by AUC and Cmax . In another study, subjects received a single dose of 600 mg (fasted) or 1,200 mg (fasted or fed) ER bi-layer tablet formulations. AUC and Cmax were equivalent between both states for the 1,200 mg ER dose. However, Tmax of 1,200 mg ER guaifenesin was later in the fed than the fasted state. ER guaifenesin is bioequivalent to corresponding OTC monograph doses of IR guaifenesin. ER guaifenesin offers a convenient 12-hour dosing alternative to 4-hour dosing of IR guaifenesin. © The Author(s) 2013.

  3. Management of gastroesophageal reflux disease and erosive esophagitis in pediatric patients: Focus on delayed-release esomeprazole

    Directory of Open Access Journals (Sweden)

    Elizabet V Guimarães

    2010-10-01

    Full Text Available Elizabet V Guimarães, Paula VP Guerra, Francisco J PennaDepartment of Pediatrics, Medical School, Universidade Federal de Minas Gerais, Belo Horizonte, BrazilObjective: To review the literature on the treatment of gastroesophageal reflux disease (GERD with emphasis on proton pump inhibitors (PPIs, particularly on delayed-release esomeprazole, and to identify properties and adverse effects of PPIs observed in the treatment of GERD in children and adolescents.Sources: Electronic search of PubMed/Medline and Cochrane Collaboration databases, and of abstracts on DDW, NASPGHAN, and ESPGHAN. We focused on controlled and randomized studies published since 2000 and identified reviews that presented a consensual position, and directives published within the last 10 years.Main results: PPIs are considered better antisecretory agents than H2-receptor antagonists. Although all PPIs are similar, they are not identical in their pharmacologic properties. For example, the acid-suppressive effect of esomeprazole, the S-isomer of omeprazole, persists for more than 16 hours after administration of the morning dose. Therefore, it can control acidity after night meals better than a single dose of omeprazole. Moreover, the onset of the suppressive effect of esomeprazole is faster. It achieves acid inhibition faster than other PPIs.Conclusion: Currently, the mainstream treatment for GERD in children is a PPI. Although PPIs are safe drugs, effective in healing erosive esophagitis, and in relieving symptoms, studies with esomeprazole have shown that this drug has as powerful an ability to inhibit acid secretion as omeprazole. It also seems that some pharmacologic properties of esomeprazole are actually better for the treatment of GERD.Keywords: gastroesophageal reflux, therapy, child, adolescent.

  4. DEET microencapsulation: a slow-release formulation enhancing the residual efficacy of bed nets against malaria vectors

    NARCIS (Netherlands)

    N'Guessan, R.; Knols, B.G.J.; Pennetier, C.; Rowland, M.

    2008-01-01

    Textile materials treated with synthetic repellents have the potential to provide protection against insect disease vectors but lack the residual activity necessary to achieve a prolonged effect or to be cost-effective. DEET MC is a formulation of DEET (N,N diethyl-m-toluamide) in which the

  5. DEET microencapsulation: a slow-release formulation enhancing the residual efficacy of bed nets against malaria vectors

    NARCIS (Netherlands)

    N'Guessan, R.; Knols, B.G.J.; Pennetier, C.; Rowland, M.

    2008-01-01

    Textile materials treated with synthetic repellents have the potential to provide protection against insect disease vectors but lack the residual activity necessary to achieve a prolonged effect or to be cost-effective. DEET MC is a formulation of DEET (N,N diethyl-m-toluamide) in which the repellen

  6. Novel electrospun nanofibrous matrices prepared from poly(lactic acid)/poly(butylene adipate) blends for controlled release formulations of an anti-rheumatoid agent.

    Science.gov (United States)

    Siafaka, Panoraia I; Barmbalexis, Panagiotis; Bikiaris, Dimitrios N

    2016-06-10

    In the present work, a series of novel formulations consisting of poly(lactic acid)/poly(butylene adipate) (PLA/PBAd) electrospun blends was examined as controlled release matrices for Leflunomide's active metabolite, Teriflunomide (TFL). The mixtures were prepared using different ratios of PLA and PBAd in order to produce nanofibrous matrices with different characteristics. Miscibility studies of the blended polymeric fibers were performed through differential scanning calorimetry (DSC) and X-ray diffractometry (XRD). Hydrolytic degradation in the prepared fibers was evaluated at 37°C using a phosphate buffered saline solution. Different concentrations of (TFL) (5, 10, 15wt.%) were incorporated into nanofibers for examining the drug release behavior in simulated body fluids (SBF), at 37°C. The drug-loaded nanofibrous formulations were further characterized by Fourier Transform Infrared Spectroscopy (FTIR) spectroscopy, DSC and XRD. Gel permeation chromatography (GPC) analysis was used to evaluate the mechanism of TFL release. Artificial neural networks (ANN) and multi-linear-regression (MLR) models were used to evaluate the effect of % content of PBAd (X1) and TFL (X2) on an initial burst effect and a dissolution behavior. It was found that PLA/PBAd nanofibers have different diameters depending on the ratio of used polyesters and added drug. TFL was incorporated in an amorphous form inside the polymeric nanofibers. In vitro release studies reveal that a drug release behavior is correlated with the size of the nanofibers, drug loading and matrix degradation after a specific time. ANN dissolution modeling showed increased correlation efficacy compared to MLR.

  7. Sucrose ester stabilized solid lipid nanoparticles and nanostructured lipid carriers: I. Effect of formulation variables on the physicochemical properties, drug release and stability of clotrimazole-loaded nanoparticles

    Science.gov (United States)

    Das, Surajit; Kiong Ng, Wai; Tan, Reginald B. H.

    2014-03-01

    The objective of this study was to develop and evaluate solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) utilizing sucrose ester as a stabilizer/emulsifier for the controlled release of drug/active. Both SLNs and NLCs were prepared using different sugar esters to screen out the most suitable stabilizer. Clotrimazole was used as a model active/drug. The effect of different formulation variables on the particle size, polydispersity index and drug encapsulation efficiency of SLNs and NLCs was evaluated and compared. SLNs and NLCs were physicochemically characterized and compared using Cryo-SEM, DSC and XRD. Furthermore, a drug release study of SLNs and NLCs was conducted. Finally, physicochemical stability (size, PI, ZP, EE) of the SLNs and NLCs was checked at 25 ± 2 °C and at 2-8 °C. Among the sucrose esters, D-1216 was found to be most suitable for both SLNs and NLCs. Formulation variables exhibited a significant impact on size, PI and EE of the nanoparticles. SLNs with ˜120 nm size, ˜0.23 PI, ˜I26I mV ZP, ˜87% EE and NLCs with ˜160 nm size, 0.15 PI, ˜I26I mV ZP, ˜88% EE were produced. Cryo-SEM revealed spherical particles with a smooth surface but did not exhibit any difference in surface morphology between SLNs and NLCs. DSC and XRD results demonstrated the disappearance of clotrimazole peak(s) in drug-loaded SLNs and NLCs. Faster drug release was observed from SLNs than NLCs. NLCs were found to be more stable than SLNs in terms of size, PI, EE and drug release. The results indicated that both SLNs and NLCs stabilized with sucrose ester D-1216 can be used as controlled release carriers although NLCs have an edge over SLNs.

  8. Formulation of two-drug controlled release non-biodegradable microparticles for potential treatment of muscles pain and spasm and their simultaneous spectrophotometeric estimation.

    Science.gov (United States)

    Khan, Shujaat A; Ahmad, Mahmood; Murtaza, Ghulam; Aamir, Muhammad N; Akhtar, Naveed; Kousar, Rozina

    2010-01-01

    The objective of this study was to formulate stable and controlled release microparticles for simultaneous delivery and UV spectrophotometric detection in combined dosage of an non-steroidal anti-inflammatory drug (NSAID) (nimesulide, NMS) and a spasmolytic agent (tizanidine, TZN) to maintain plasma concentration that may increase patients compliance, improved therapeutic efficacy, The aim was also to reduce severity of upper GI side effects of NMS because of alteration in delivery pattern via slow release of drug from microparticles and to increase the benefits of spasticity and disability for spastic patients by administering TZN in a modified release formulation as these two drugs are often prescribed in combination for the management of pain associated with muscles spasm. Ethyl cellulose was used as a retardant polymer. Drug-polymer and drug-drug compatibility study were conducted by different analytical tests. Microparticles were prepared by coacervation thermal change method. The prepared microparticles were characterized for their micromeritics and drug loading. The prepared microparticles were light yellow, free flowing and spherical in shape. The drug-loaded microparticles showed 87% and 91% entrapment efficiency of NMS and TZN, respectively, and release was extended up to 10 h. The infrared spectra, differential scanning calorimetry thermograms and XRD spectra showed the stable character of both the drugs in the drug-loaded microparticles. The in vitro release study of microparticles was performed in phosphate buffer pH 6.8. Linearity was observed in the concentration range of 5.0-30.0 microg/mL of NMS and 0.5-3.0 microg/mL of TZN. The microparticles have a potential for the prolongation and simultaneous delivery of the NIM and TIZ. The proposed UV method for simultaneous detection can be used for routine analysis of combined dosage form.

  9. The efficacy and safety of a controlled release formulation of salbutamol in the management of patients with asthma in Nairobi, Kenya.

    Science.gov (United States)

    Gathua, S N; Aluoch, J A

    1990-12-01

    The treatment of asthma in Africa is influenced by cultural and environmental factors as well as the availability of drugs. Poor compliance with regard to long-term maintenance treatment of chronic asthma is also a problem in Africa. The present study reports on 45 patients from 2 centres in Nairobi treated with 8 mg twice daily of an oral controlled release formulation of salbutamol ("Volmax"). The treatment produced a significant improvement in lung function measured by the PEFR compared with baseline data on previous therapy. Controlled release salbutamol was rated as effective or very effective by 84.2% of patients and for 81.6% of patients their physicians preferred this preparation to the therapy used before the study. Side effects were infrequent and usually occurred during the first few days of treatment. The study which is the first report in Africa to assess this novel formulation of salbutamol in a group of African patients, demonstrates that controlled release salbutamol 8 mg administered twice daily is safe and effective, offering benefits over current therapies in the treatment of asthma.

  10. Formulation development of fast releasing oral thin films of levocetrizine dihydrochloride with Eudragit® Epo and optimization through Taguchi orthogonal experimental design

    Directory of Open Access Journals (Sweden)

    P K Lakshmi

    2011-01-01

    Full Text Available The aim of this study was to develop a fast releasing oral polymeric film, prepared using the solvent casting method, with good mechanical properties, instant disintegration and dissolution, an acceptable taste in the oral cavity. Levocetirizine dihydrochloride, an antihistamine, was incorporated to relieve the symptoms of allergic rhinitis. Four batches of films with drug were prepared using different combinations of polymers and plasticizers Eudragit; EPO, HPMC E 5 LV, and PVA were the selected polymers. Glycerin, dibutyl phthalate, propylene glycol, and PEG 400 were the selected plasticizers. The resultant films were evaluated for weight variation, assay, content uniformity, folding endurance, thickness, tensile strength, percent elongation, surface pH, in vitro disintegration and in vitro dissolution. The formulations from the preliminary trial were analyzed using Taguchi OA experimental design, which was applied to optimize the type of polymers, concentration of polymers, plasticizer, and sweetener based on their disintegration data at three different levels. The optimized films disintegrated in less than 30s, releasing 70-90% of drug within 2 mins. The percentage release varied with the type of polymer and concentration of polymer. The films made with EPO released 96% of drug in 2 mins, which was the best release among all.

  11. Development and application of a delayed-release anthelmintic intra-ruminal bolus system for experimental manipulation of nematode worm burdens.

    Science.gov (United States)

    Carlsson, Anja M; Wilson, Kenneth; Irvine, R Justin

    2012-07-01

    In order to quantify the impact of parasites on host population dynamics, experimental manipulations that perturb the parasite-host relationship are needed but, logistically, this is difficult for wild hosts. Here, we describe the use of a delayed-release anthelmintic delivery system that can be administered when the hosts can be captured and its activity delayed until a more appropriate period in the host-parasite cycle. Our model system is Svalbard reindeer infected with a nematode parasite, Marshallagia marshalli, which appears to accumulate during the Arctic winter. To determine the extent to which this occurs and the effect on host fitness, reindeer need to be treated with anthelmintics in late autumn but they can only be caught and handled in April. To solve this problem, we devised an intra-ruminal capsule that releases the anthelmintic from up to 6 months after being administered. The capsule was trialed in cannulated sheep and red deer to determine optimum capsule orifice size and release rates. Capsules were estimated to release placebo for 100-153 days followed by abamectin for 22-34 days. To test the efficacy of treatment in reindeer, capsules were administered in April and retrieved in October. All capsules had fully released the anthelmintic and treated reindeer had significantly lower worm burdens than controls. Thus, success of this system allows repeated treatment over several years to test the effect of winter parasitism on host fitness.

  12. Evaluation of a 12-Hour Sustained-Release Acetaminophen (Paracetamol) Formulation: A Randomized, 3-Way Crossover Pharmacokinetic and Safety Study in Healthy Volunteers.

    Science.gov (United States)

    Yue, Yong; Collaku, Agron; Liu, Dongzhou J

    2017-08-16

    Acetaminophen (paracetamol) is a first-line treatment for mild and moderate pain. A twice-daily sustained-release (SR) formulation may be more convenient for chronic users than standard immediate-release (IR) acetaminophen. This randomized, 3-way crossover study evaluated pharmacokinetics and safety of single-dose 1500- and 2000-mg SR acetaminophen formulations and 2 doses of IR acetaminophen 1000 mg given 6 hours apart in healthy adults (n = 14). Primary outcome was time that plasma acetaminophen concentration was ≥4 μg/mL (TC≥4μg/mL ). Key secondary outcomes were area under the plasma concentration-time curve (AUC) from time 0 to time t, when plasma acetaminophen was detectable (AUC0-t ), AUC from 0 to infinity (AUC0-inf ), and maximum plasma acetaminophen concentration (Cmax ). TC≥4μg/mL from 2000-mg SR acetaminophen was similar to that from 2 doses of IR acetaminophen, whereas TC≥4μg/mL for 1500-mg SR acetaminophen was significantly shorter than that for IR acetaminophen (P = .004). The extent of acetaminophen absorption from 2000-mg SR and 2 doses of the IR formulation was similar and within bioequivalence limits with regard to AUC0-12 , AUC0-t , and AUC0-inf . The extent of acetaminophen absorption from 1500-mg SR was significantly lower than that from IR acetaminophen. The 2000-mg SR represents a potential candidate formulation for 12-hour dosing with acetaminophen. © 2017, The American College of Clinical Pharmacology.

  13. Extent of use of immediate-release formulations of calcium channel blockers as antihypertensive monotherapy by primary care physicians: multicentric study from Bahrain.

    Directory of Open Access Journals (Sweden)

    Sequeira R

    2002-07-01

    Full Text Available BACKGROUND: The issue of cardiovascular safety of calcium channel blockers (CCBs has been widely debated in view of reflex increase in sympathetic activity induced by immediate release (IR / short acting formulations. It is generally agreed that such CCBs should not be used alone in the management of hypertension. AIMS: We have determined the extent to which primary care physicians prescribe CCBs as monotherapy, especially the immediate release formulations, in the management of uncomplicated hypertension and diabetic hypertension - with an emphasis upon the age of the patients. SETTING, DESIGN AND METHODS: A retrospective prescription-based study was carried out in seven out of 18 Health Centres in Bahrain. The study involved a registered population of 229,300 representing 46% of registered individuals, and 35 physicians representing 43% of all primary care physicians. The data was collected between November 1998 and January 1999 using chronic dispensing cards. RESULTS: In all categories CCBs were the third commonly prescribed antihypertensive as monotherapy, with a prescription rate of 11.1% in uncomplicated hypertension, 18% in diabetic hypertension and 20.1% in elderly patients above 65 years of age. Nifedipine formulations were the most extensively prescribed CCBs. Almost half of the CCB-treated patients were on IR-nifedipine, whereas IR-diltiazem and IR-verapamil, and amlodipine were infrequently prescribed. CONCLUSION: Prescription of IR-formulations of CCBs as monotherapy by primary care physicians does not conform with recommended guidelines. In view of concerns about the safety of such practice, measures to change the prescribing pattern are required.

  14. Estudio de bioequivalencia de dos formulaciones de tabletas de carbamazepina de liberación retardada Study of bioequivalence of two carbamazepine retard-release tablet formulations

    Directory of Open Access Journals (Sweden)

    2000-03-01

    Full Text Available En 12 voluntarios sanos se efectuó un estudio de bioequivalencia de dos preparados comerciales de carbamazepina en tabletas de liberación retardada. Este estudio permitió comparar la biodisponibilidad de la formulación de referencia Tegretol® Retard de Ciba Geigy elaborado en Colombia por Novartis, y la formulación de prueba Carbamazepina MK Retard, de Tecnoquímicas. Para evaluar la bioequivalencia se determinaron las curvas de concentración plasmática vs tiempo de las dos formulaciones y se calcularon las áreas bajo la curva (AUC y las concentraciones máximas (Cmáx. Para la formulación de prueba el intervalo de confianza del 90% para el AUC estuvo entre 95.7 y 100.7% y para el C(máx entre el 88.6 y el 106.1%. Para ambas determinaciones el rango de aceptación, según normas internacionales, está entre 80 y 125% de la formulación de referencia. Esto demuestra la bioequivalencia de las dos formulaciones. A study of the bioequivalence of two comercial carbamazepine retard-release formulations was carried out in 12 healthy volunteers. Studies of bioequivalence allow to compare the bioavailability of the innovator formulation with generic, alternative or branch formulations. In order to evaluate the bioequivalence, plasma carbamazepine concentration/time curves were obtained for the Tegretol® Retard Tablets –reference formulationand for the test formulation; the area under each curve and the maximum concentration were calculated. After the calculation, statistical analysis of data for the area under the curve of the Carbamazepine Retard Tablets –test formulation, was between 95.7% and 100.7 % and the maximum concentration of the test formulation was between 88.6% and 106.1%; both parameters with the 90% confidence interval. Since the acceptance range was determined to be between 80.0% and 125.0% of the reference formulation, we concluded from this study that the two formulations are bioequivalent.

  15. 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.

  16. Effect of permeation enhancers on the release and permeation kinetics of Lincomycin hydrochloride gel formulations through mouse skin

    Directory of Open Access Journals (Sweden)

    Panigrahi L

    2006-01-01

    Full Text Available Lincomycin hydrochloride is a systemic antibiotic, which is active against most common gram positive bacteria. It has proved to be excellent for infectious diseases like acne, anthrax, pneumonia, and also for the treatment of furunculosis, carbuncles, impetigo, burns and wounds, carrying to gram positive bacteria. Gels were prepared using carbopol 940 as gelling agent, and isopropyl myristate and dimethyl sulfoxide as permeation enhancer. The formulations were evaluated for drug content, viscosity, pH, extrudability, homogeneity, skin irritation test, spreadability, and gel strength. A formulation containing 1.5% carbopol with 10% isopropyl myristate, showed better in vitro skin permeation through abdominal mouse skin, and was found to be the best.

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

    Directory of Open Access Journals (Sweden)

    K Pawan Gaur

    2012-01-01

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

  18. Pharmacokinetic comparison of sustained- and immediate-release formulations of cilostazol after multiple oral doses in fed healthy male Korean volunteers

    Directory of Open Access Journals (Sweden)

    Kim YH

    2015-07-01

    Full Text Available Yo Han Kim,1 Jong-Lyul Ghim,2 Jin Ah Jung,2 Sang-Heon Cho,3 Sangmin Choe,4 Hee Youn Choi,1 Kyun-Seop Bae,1 Hyeong-Seok Lim1 1Department of Clinical Pharmacology and Therapeutics, College of Medicine, University of Ulsan, Asan Medical Center, Seoul, 2Department of Clinical Pharmacology, Inje University, Busan Paik Hospital, Busan, 3Department of Clinical Pharmacology, Inha University Hospital, Inha University School of Medicine, Incheon, 4Clinical Trials Center, Pusan National University Hospital, Busan, Republic of Korea Background: A new extended-release form of cilostazol has recently been developed. This study was conducted to compare the pharmacokinetic characteristics of sustained-release (SR and immediate-release (IR formulations of cilostazol after multiple oral doses in healthy male Korean volunteers.Methods: This was an open-label, randomized, multiple-dose, crossover study conducted in 30 healthy Korean subjects. In each treatment period, subjects received oral doses of 200 mg SR formulation every 24 hours or 100 mg IR formulation every 12 hours for 5 consecutive days in a fed state, with a washout period of 9 days. The plasma concentrations of cilostazol and its metabolites were determined using a validated liquid chromatography-tandem mass spectrometry method. The area under the plasma concentration–time curve within a dosing interval (AUCT, the measured peak plasma concentration at steady state (Cmax,ss, and the time to reach Cmax,ss (tmax,ss were analyzed using a noncompartmental method. Results: A total of 24 healthy male subjects completed the study. The mean (standard deviation [SD] AUCT (96–120 hours values for SR and IR were 27,378.0 (10,301.6 ng·h/mL and 27,860.3 (7,152.3 ng·h/mL, respectively. The mean (SD Cmax,ss values were 2,741.4 (836.0 ng/mL and 2,051.0 (433.2 ng/mL, respectively. The median tmax,ss values were 8.0 hours and 4.0 hours, respectively. The geometric mean ratios (90% confidence intervals of

  19. Formulation Development and Evaluation of Drug Release Kinetics from Colon-Targeted Ibuprofen Tablets Based on Eudragit RL 100-Chitosan Interpolyelectrolyte Complexes.

    Science.gov (United States)

    Ofokansi, Kenneth Chibuzor; Kenechukwu, Franklin Chimaobi

    2013-01-01

    Colon-targeted drug delivery systems (CTDDSs) could be useful for local treatment of inflammatory bowel diseases (IBDs). In this study, various interpolyelectrolyte complexes (IPECs), formed between Eudragit RL100 (EL) and chitosan (CS), by nonstoichiometric method, and tablets based on the IPECs, prepared by wet granulation, were evaluated as potential oral CTDDSs for ibuprofen (IBF). Results obtained showed that the tablets conformed to compendial requirements for acceptance and that CS and EL formed IPECs that showed pH-dependent swelling properties and prolonged the in vitro release of IBF from the tablets in the following descending order: 3 : 2 > 2 : 3 > 1 : 1 ratios of CS and EL. An electrostatic interaction between the carbonyl (-CO-) group of EL and amino (-NH3 (+)) group of CS of the tablets formulated with the IPECs was capable of preventing drug release in the stomach and small intestine and helped in delivering the drug to the colon. Kinetic analysis of drug release profiles showed that the systems predominantly released IBF in a zero-order manner. IPECs based on CS and EL could be exploited successfully for colon-targeted delivery of IBF in the treatment of IBDs.

  20. Floating matrix tablets based on low density foam powder: effects of formulation and processing parameters on drug release.

    Science.gov (United States)

    Streubel, A; Siepmann, J; Bodmeier, R

    2003-01-01

    The aim of this study was to develop and physicochemically characterize single unit, floating controlled drug delivery systems consisting of (i). polypropylene foam powder, (ii). matrix-forming polymer(s), (iii). drug, and (iv). filler (optional). The highly porous foam powder provided low density and, thus, excellent in vitro floating behavior of the tablets. All foam powder-containing tablets remained floating for at least 8 h in 0.1 N HCl at 37 degrees C. Different types of matrix-forming polymers were studied: hydroxypropyl methylcellulose (HPMC), polyacrylates, sodium alginate, corn starch, carrageenan, gum guar and gum arabic. The tablets eroded upon contact with the release medium, and the relative importance of drug diffusion, polymer swelling and tablet erosion for the resulting release patterns varied significantly with the type of matrix former. The release rate could effectively be modified by varying the "matrix-forming polymer/foam powder" ratio, the initial drug loading, the tablet geometry (radius and height), the type of matrix-forming polymer, the use of polymer blends and the addition of water-soluble or water-insoluble fillers (such as lactose or microcrystalline cellulose). The floating behavior of the low density drug delivery systems could successfully be combined with accurate control of the drug release patterns.

  1. Calmodulin modulates the delay period between release of calcium from internal stores and activation of calcium influx via endogenous TRP1 channels.

    Science.gov (United States)

    Vaca, Luis; Sampieri, Alicia

    2002-11-01

    In the present study we have explored the role of calmodulin (CaM) and inositol 1,4,5-trisphosphate receptor (IP(3)R) in the communication process activated after the release of calcium from the endoplasmic reticulum (ER) and the activation of calcium influx via endogenous TRP1 channels from Chinese hamster ovary cells. Experiments using combined rapid confocal calcium and electrophysiology measurements uncovered a consistent delay of around 900 ms between the first detectable calcium released from the ER and the activation of the calcium current. This delay was evident with two different methods used to release calcium from the ER: either the blockade of the microsomal calcium ATPase with thapsigargin or activation of bradykinin receptors linked to the IP(3) cascade. Direct application of IP(3) or a peptide from the NH(2)-terminal region of the IP(3)R activated store operated calcium, reducing the delay period. Introduction of CaM into the cell via the patch pipette increased the delay period from 900 +/- 100 ms to 10 +/- 2.1 s (n = 18). Furthermore, the use of selective CaM antagonists W7 and trifluoperazine maleate resulted in a substantial reduction of the delay period to 200 +/- 100 ms with 5 microm trifluoperazine maleate (n = 16) and 150 +/- 50 ms with 500 nm W7 (n = 22). CaM reduced also the current density activated by thapsigargin or brandykinin to about 60% from control. The CaM antagonists did not affect significantly the current density. The results presented here are consistent with an antagonistic effect of IP(3)R and CaM for the activation of store operated calcium after depletion of the ER. The functional competition between the activating effect of IP(3)R and the inhibiting effect of CaM may modulate the delay period between the release of calcium from the ER and the activation of calcium influx observed in different cells, as well as the amount of current activated after depletion of the ER.

  2. FORMULATION OF FLOATING TABLETS OF MEFENAMIC ACID WITH DIFFERENT GRADES OF HYDROXY PROPYL METHYL CELLULOSE POLYMER AND STUDYING THE RELEASE PROFILES

    Directory of Open Access Journals (Sweden)

    Ramanathan.G, Kavitha.K

    2010-09-01

    Full Text Available Hydrodynamically balanced system (HBS or Floating tablets has gained importance in recent days to improve absorption of drugs especially those that are absorbed from stomach and small intestine. In the present study, an attempt was made to fabricate and evaluate an HBS dosage form of Mefenamic Acid tablet The different viscosity grades of Hydroxypropylmethyl cellulose polymer like HPMC K100, HPMC K4M, HPMC KV600, HPMC K50 was incorpated as hydrophilic swellable polymers for preparing matrix-floating tablets. Sodium bicarbonate was incorporated as a gas-generating agent. The prepared floating tablets were evaluated for the physical parameters like thickness, hardness, friability, drug content, floating lag time, floating time and Invitro dissolution studies. The mechanism of drug release was anomalous type and depends upon the viscosity of polymers, which was mainly concluded as the major controlling factor for the drug release. The results showed that the formulation containing Drug: Hpmc kv600 in the ratio of 1:0.5 is suitable for the formulation of gastroretentive floating tablets of mefenamic acid

  3. In vitro solubility, dissolution and permeability studies combined with semi-mechanistic modeling to investigate the intestinal absorption of desvenlafaxine from an immediate- and extended release formulation

    DEFF Research Database (Denmark)

    Franek, F; Jarlfors, A; Larsen, F.

    2015-01-01

    Desvenlafaxine is a biopharmaceutics classification system (BCS) class 1 (high solubility, high permeability) and biopharmaceutical drug disposition classification system (BDDCS) class 3, (high solubility, poor metabolism; implying low permeability) compound. Thus the rate-limiting step for desve......Desvenlafaxine is a biopharmaceutics classification system (BCS) class 1 (high solubility, high permeability) and biopharmaceutical drug disposition classification system (BDDCS) class 3, (high solubility, poor metabolism; implying low permeability) compound. Thus the rate-limiting step...... for desvenlafaxine absorption (i.e. intestinal dissolution or permeation) is not fully clarified. The aim of this study was to investigate whether dissolution and/or intestinal permeability rate-limit desvenlafaxine absorption from an immediate-release formulation (IRF) and Pristiq®, an extended release formulation...... (ERF). Semi-mechanistic models of desvenlafaxine were built (using SimCyp®) by combining in vitro data on dissolution and permeation (mechanistic part of model) with clinical data (obtained from literature) on distribution and clearance (non-mechanistic part of model). The model predictions...

  4. Formulation and evaluation of gelatin micropellets of aceclofenac: Effect of process variables on encapsulation efficiency, particle size and drug release

    Directory of Open Access Journals (Sweden)

    Sahoo S

    2008-01-01

    Full Text Available In the present study aceclofenac-gelatin micropellets were prepared by the cross linking technique using gluteraldehyde as cross linking agent and characterized by X-ray diffractometry, differential scanning calorimetry and scanning electron microscopy. The effect of drug: polymer ratio, temperature of oil phase, amount of gluteraldehyde and stirring time was studied with respect to entrapment efficiency, micropellet size and drug release characteristics. Spherical micropellets having an entrapment efficiency of 57% to 97% were obtained. Differential scanning calorimetric analysis confirmed the absence of any drug-polymer interaction. The micromeritic studies of micropellets show improved flow property. The entrapment efficiency, micropellet size and drug release profile was altered significantly by changing various processing parameters.

  5. FORMULATION AND EVALUATION OF EFFERVESCENT GASTRO-RETENTIVE FLOATING TABLETS FOR CONTROLLED RELEASE OF AN ANTI-ULCER COMPOUND

    Directory of Open Access Journals (Sweden)

    Aleksandar Aleksovski

    2013-02-01

    Full Text Available Effervescent floating gastro-retentive matrix tablets present novel and promising approach towards targeted and controlled drug delivery in the stomach and in the upper part of the small intestine. This kind of dosage form could be obtained by combining in a suitable ratio effervescent compounds and hydrophilic/hydrophobic polymer/s. The aim of our investigation was to develop controlled release effervescent matrix tablet which will float over the gastric media for longer than 8 hours and will release the active compound in a continuous manner over 8 hours period. We used ranitidine HCl as a model drug which has narrow absorption window in the upper small intestine, and is a good candidate for this type of dosage forms. We employed sodium bicarbonate and citric acid as effervescent compounds and two different types of hydroxypropyl methylcellulose (HPMC K4M and HPMC K15M as a controlled release hydrophilic polymer. Three batches of tablets were produced (one containing HPMC K4M, other containing HPMC K15M, and the third containing 1:1 mixture of these two polymers and every batch was compressed with two different forces 5.5 kN and 4.7 kN, so completely six probes of tablets were made. All six probes complied the pharmacopoeial requirements concerning mass uniformity, content, friability and hardness. All six probes tended to float fast to the surface of the medium and tend to hydrate and swell fast enough which actions provided controlled release of the compound over period of 8 hours. No significant differences in the dissolution profiles of all six probes were noticed during the investigation.

  6. Formulation of porous poly(lactic-co-glycolic acid) microparticles by electrospray deposition method for controlled drug release

    Energy Technology Data Exchange (ETDEWEB)

    Hao, Shilei; Wang, Yazhou; Wang, Bochu, E-mail: wangbc2000@126.com; Deng, Jia; Zhu, Liancai; Cao, Yang

    2014-06-01

    In the present study, the electrospray deposition was successfully applied to prepare the porous poly(lactic-co-glycolic acid) (PLGA) microparticles by one-step processing. Metronidazole was selected as the model drug. The porous PLGA microparticles had high drug loading and low density, and the porous structure can be observed by scanning electron microscope (SEM) and transmission electron microscopy (TEM). The production time has been shortened considerably compared with that of the traditional multi-emulsion method. In addition, no chemical reaction occurred between the drug and polymer in the preparation of porous microparticles, and the crystal structure of drug did not change after entrapment into the porous microparticles. The porous microparticles showed a sustained release in the simulated gastric fluid, and the release followed non-Fickian or case II transport. Furthermore, porous microparticles showed a slight cytotoxicity in vitro. The results indicated that electrospray deposition is a good technique for preparation of porous microparticles, and the low-density porous PLGA microparticles has a potential for the development of gastroretentive systems or for pulmonary drug delivery. - Highlights: • The porous PLGA microparticles were successfully prepared by the electrospray deposition method at one step. • The porous microparticles had high loading capacity and low density. • The microparticle showed a sustained release in the simulated gastric liquid. • The microparticles showed a slight cytotoxicity in vitro.

  7. Fast-track vs. delayed insertion of the levonorgestrel-releasing intrauterine system after early medical abortion - a randomized trial.

    Science.gov (United States)

    Korjamo, Riina; Mentula, Maarit; Heikinheimo, Oskari

    2017-08-05

    To compare levonorgestrel (LNG) 52-mg intrauterine system (IUS) expulsion rates with fast-track (≤3 days) or delayed (2-4 weeks) insertion following mifepristone and misoprostol medical abortion. In this pilot trial, we randomized 108 women at ≤63 days' gestation to fast-track (n=55) or delayed (n=53) insertion. Follow-up visits occurred at 2-4 weeks, 3 months and 1 year. We assessed total and partial expulsion at 3 months and 1 year, adverse effects and bleeding profiles. We had follow-up data at 3 months and 1 year for 41 (74.5%) and 37 (69.8%) women in the fast-track group and 31 (56.4%) and 28 (52.8%) women in the delayed group. By 3 months, expulsion occurred in six (12.5%) women after fast-track and one (2.3%) woman after delayed insertion [risk ratio (RR) 5.50, 95% confidence interval (CI) 0.69-43.90]; most (n=5) of these were partial expulsions in the fast-track group. By 1 year, expulsion had occurred in seven (14.6%) and five (11.5%) women in the fast-track and delayed groups, respectively (RR 1.28, 95% CI 0.44-3.75). We found no differences in rates of vacuum aspiration, residual tissue, infection and bleeding or bleeding patterns within 3 months of insertion. Fast-track insertion of the LNG 52-mg IUS after medical abortion is feasible but may result in higher expulsion rates compared to delayed insertion. Due to lack of statistical power and high lost-to-follow-up rates, we were unable to fully address this question. Fast-tract initiation of LNG 52-mg IUS contraception after medical abortion is feasible. It results in higher expulsion rates than delayed insertion but may improve postabortal intrauterine contraception uptake. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Effect of a controlled-release drug delivery system made of oleanolic acid formulated into multivesicular liposomes on hepatocellular carcinoma in vitro and in vivo

    Directory of Open Access Journals (Sweden)

    Luo YL

    2016-07-01

    Full Text Available Yuling Luo, Zhongbing Liu, Xiaoqin Zhang, Juan Huang, Xin Yu, Jinwei Li, Dan Xiong, Xiaoduan Sun, Zhirong Zhong Department of Pharmaceutical Sciences, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan,People’s Republic of ChinaAbstract: The aim of the present study was to develop a novel dosage form of multivesicular liposomes for oleanolic acid (OA to overcome its poor solubility, prolong therapeutic drug levels in the blood, and enhance the antitumor effect on hepatocellular carcinoma. OA-encapsulated multivesicular liposomes (OA-MVLs were prepared by a double-emulsion method, and the formulation was optimized by the central composite design. The morphology, particle size, and drug-loading efficiency of OA-MVLs were investigated. Furthermore, OA-MVLs were also characterized both in vitro and in vivo. The results showed that OA-MVLs were spherical particles with an average particle size of 11.57 µm and an encapsulation efficiency of 82.3%±0.61%. OA-MVLs exhibited a sustained-release pattern in vitro, which was fitted to Ritger–Peppas equation. OA-MVLs inhibited the growth of human HepG2 cells which was confirmed by the MTT assay and fluorescence microscopy detection. The in vivo release of OA from OA-MVLs exhibited a sustained manner, indicating a longer circulation time compared to OA solution. The in vivo toxicity study indicated that medium-dose OA-MVLs exerted no toxic effect on the hosts. Importantly, OA-MVLs suppressed the growth of murine H22 hepatoma and prolonged the survival of tumor-bearing mice. In conclusion, the poorly soluble OA could be encapsulated into MVLs to form a novel controlled-release drug delivery system. The present study may hold promise for OA-MVLs as a new dosage form for sustained-release drug delivery in cancer therapy.Keywords: oleanolic acid, multivesicular liposomes, murine hepatocellular carcinoma, controlled release, cancer therapy

  9. Immediate versus delayed initiation of the levonorgestrel-releasing intrauterine system following medical termination of pregnancy - 1 year continuation rates: a randomised controlled trial.

    Science.gov (United States)

    Korjamo, R; Mentula, M; Heikinheimo, O

    2017-06-26

    To assess the 1-year continuation rates and new pregnancies following immediate versus delayed insertion of the levonorgestrel-releasing intrauterine system (LNG-IUS) after medical termination of pregnancy (MTOP) up to 20 weeks of gestation. A randomised controlled trial. Helsinki University Hospital, Finland, January 2013 to December 2014. A total of 267 women requesting MTOP and planning LNG-IUS for post-MTOP contraception. Insertion of LNG-IUS occurred immediately (0-3 days) or after a delay (2-4 weeks) following MTOP. Follow-up visits were at 3 months and 1 year after MTOP. LNG-IUS use at 1 year after MTOP. Women were randomised to immediate (n = 134) or delayed (n = 133) insertion of the LNG-IUS, and 133 and 131 were analysed; 127 (95.5%) women received immediate insertion and 111 (84.7%) women had delayed insertion of the LNG-IUS (risk ratio [RR] 1.13, 95% CI 1.04-1.22). The verified numbers of women continuing the LNG-IUS use at 1 year were 83 (62.4%) and 52 (39.7%) (RR 1.57, 95% CI 1.23-2.02). The numbers of new pregnancies were 6 (4.5%) and 16 (12.2%) (RR 0.37, 95% CI 0.15-0.91), and numbers of subsequent TOPs were 4 (3.0%) and 5 (3.8%) (RR 0.79, 95% CI 0.22-2.87). Immediate insertion of the LNG-IUS following MTOP resulted in higher 1-year continuation rates compared with delayed insertion. In addition, those receiving immediate insertion demonstrated a decreased new pregnancy rate, but no difference in the numbers of another TOP. Immediate LNG-IUS insertion after MTOP results in a higher 1-year continuation compared with delayed insertion. © 2017 Royal College of Obstetricians and Gynaecologists.

  10. Design and evaluation of an extended-release matrix tablet formulation; the combination of hypromellose acetate succinate and hydroxypropylcellulose

    Directory of Open Access Journals (Sweden)

    Sachiko Fukui

    2017-03-01

    Full Text Available The purpose of this study was to develop an extended-release (ER matrix tablet that shows robust dissolution properties able to account for the variability of pH and mechanical stress in the GI tract using a combination of enteric polymer and hydrophilic polymer. Hypromellose acetate succinate (HPMCAS and hydroxypropylcellulose (HPC were selected as ER polymers for the ER matrix tablet (HPMCAS/HPC ER matrix tablet. Oxycodone hydrochloride was employed as a model drug. Dissolution properties of the HPMCAS/HPC ER matrix tablets were evaluated and were not affected by the pH of the test medium or paddle rotating speed. In a USP apparatus 3 (bio-relevant dissolution method, dissolution profiles of the HPMCAS/HPC ER matrix tablets containing oxycodone hydrochloride were similar to that of the reference product (OxyContin. Moreover, in vivo performance after oral administration of the HPMCAS/HPC ER matrix tablets to humans was simulated by GastroPlus based on dissolution profiles from the USP apparatus 3. The plasma concentration-time profile simulated was similar to that of the reference product. These results suggest that the combination of HPMCAS and HPC shows a robust dissolution profile against pH and paddle rotating speed and indicates the appropriate extended-release profile in humans.

  11. Improved Release of Celecoxib from High Drug Loading Amorphous Solid Dispersions Formulated with Polyacrylic Acid and Cellulose Derivatives.

    Science.gov (United States)

    Xie, Tian; Taylor, Lynne S

    2016-03-07

    Amorphous solid dispersions (ASDs) have been extensively exploited as a strategy for improving the dissolution performance of poorly water-soluble drugs. However, factors underpinning the observed dissolution profiles are not clearly understood, and the choice of polymeric carriers is largely empirical. In the current study, the dissolution performance of a high drug loading ASD containing the poorly water-soluble, anti-inflammatory agent, celecoxib, was optimized by using binary polymers combinations. Polyacrylic acid (PAA), a highly water-soluble polymer, was used to substantially increase the dissolution rate of the drug, while hydroxypropyl methyl cellulose (HPMC) or HPMC acetate succinate (HPMCAS) were added to stabilize the solid amorphous matrix against crystallization upon hydration, as well as to maintain supersaturation. Quantitative measurements of the impact of the polymers on the solution nucleation and growth rates of celecoxib revealed that, while the cellulose derivatives are effective nucleation inhibitors, it is more difficult to completely prevent crystal growth in solutions containing seed crystals, in particular at high supersaturations. Therefore, it is critical to prevent the formation of crystals in the dissolving matrix during dissolution. By using certain ratios of HPMC and PAA, both rapid release as well as crystallization inhibition could be achieved, even at high drug loadings. Utilizing combinations of polymers may therefore be useful to tailor release profiles while providing optimized crystallization inhibition.

  12. Development and Validation of HPTLC Method for Estimation of Carbamazepine in Formulations and Its In Vitro Release Study

    Directory of Open Access Journals (Sweden)

    Rashmin B. Patel

    2011-01-01

    Full Text Available A new, simple, and rapid high-performance thin-layer chromatographic method was developed and validated for quantitative determination of Carbamazepine. Carbamazepine was chromatographed on silica gel 60 F254 TLC plate using ethyl acetate-toluene-methanol (5.0 + 4.0 + 1.0 v/v/v as mobile phase. Carbamazepine was quantified by densitometric analysis at 285 nm. The method was found to give compact spots for the drug (Rf=0.47 ± 0.01. The linear regression analysis data for the calibration plots showed good linear relationship with r2=.9995 in the concentration range 100–600 ng/spot. The method was validated for precision, recovery, repeatability, and robustness as per the International Conference on Harmonization guidelines. The minimum detectable amount was found to be 16.7 ng/spot, whereas the limit of quantitation was found to be 50.44 ng/spot. Statistical analysis of the data showed that the method is precise, accurate, reproducible, and selective for the analysis of Carbamazepine. The method was successfully employed for the estimation of equilibrium solubility, quantification of Carbamazepine as a bulk drug, in commercially available preparation, and in-house developed mucoadhesive microemulsion formulations and solution.

  13. Effect of advanced blood pressure control with nifedipine delayed-release tablets on the blood pressure in patients underwent nasal endoscope surgery

    Institute of Scientific and Technical Information of China (English)

    Qing-Hua Xiao; Li Yang; Rong-Ping Chen; Wei-Dong Qiu

    2016-01-01

    Objective:To explore the effect of advanced blood pressure control with nifedipine delayed-release tablets on the blood pressure in patients underwent nasal endoscope surgery and its feasibility.Methods:A total of 80 patients who were admitted in ENT department from June, 2012 to June, 2015 for nasal endoscope surgery were included in the study and randomized into the observation group and the control group with 40 cases in each group. The patients in the observation group were given nifedipine delayed-release tablets for advanced blood pressure control before operation, and were given routine blood pressure control during operation; while the patients in the control group were only given blood pressure control during operation. The changes of blood pressure, mean central arterial pressure, and heart rate before anesthesia (T0), after intubation (T1), during operation (T2), extubation when waking (T3), 30 min after extubation (T4), and 3 h after back to wards (T5) in the two groups were compared. The intraoperative situation and the surgical field quality in the two groups were compared.Results: SBP, DBP, and MAP levels at T1-5 in the two groups were significantly lower than those at T0. SBP, DBP, and MAP levels at T2 were significantly lower than those at other timing points, and were gradually recovered after operation, but were significantly lower than those at T0. The effect taking time of blood pressure reducing, intraoperative nitroglycerin dosage, and postoperative wound surface exudation amount in the observation group were significantly less than those in the control group. The surgical field quality scores in the observation group were significantly superior to those in the control group.Conclusions:Advanced blood pressure control with nifedipine delayed-release tablets can stabilize the blood pressure during the perioperative period in patients underwent nasal endoscope surgery, and enhance the surgical field qualities.

  14. 替莫唑胺局部缓释制剂的研究进展%Advances in Locally Sustained Release Formulations of Temozolomide

    Institute of Scientific and Technical Information of China (English)

    张晶晶; 王永峰; 王国成; 杨海龙; 范立君

    2014-01-01

    近年来,为更有效地发挥替莫唑胺对神经胶质瘤的治疗活性,局部、缓释给药成为替莫唑胺的研究热点。本文简述了几种研发中的替莫唑胺的局部缓释新制剂,其中替莫唑胺-聚酸酐缓释微球( TMZ-pCPP:SA)由于聚酸酐表面溶蚀等特性,具有良好的缓释特性,鼠颅内植入试验显示,比口服替莫唑胺具有更好的治疗效果,因此替莫唑胺-聚酸酐缓释微球作为颅内缓释制剂具有极为光明的前景。%In order to overcome the toxicity and side effects of systemic administration of temozolomide, locally sustained release administration of temozolomide has become the hot research topics in recent years. This paper reviewed a number of newly locally and sustained release fomulations of temozolomide. Among them, temozolomide-polyanhydrid ( TMZ-pCPP:SA) ,for its character of surface erosion, has the favourable sustained release property. The intracranial implantation test of rats indicated that TMZ-pCPP:SA had better treatment effects, less toxicity and side effects than oral administration of temozolomide. Thus, TMZ-pCPP:SA as an intracranial sustained release formulation has a bright future.

  15. The use of formulation technology to assess regional gastrointestinal drug absorption in humans.

    Science.gov (United States)

    Basit, Abdul W; Podczeck, Fridrun; Newton, J Michael; Waddington, Wendy A; Ell, Peter J; Lacey, Larry F

    2004-02-01

    The aim of this study was to assess the feasibility of using oral modified-release formulations for the purposes of site-specific targeting and regional drug absorption assessment in man. An immediate release pellet formulation containing ranitidine as the model drug of choice for the study was fabricated by extrusion-spheronisation, and then film coated with either the enteric polymer polyvinyl acetate phthalate or the bacteria-degradable polymer amylose, in combination with ethylcellulose, to effect drug release within the small intestine and colon, respectively. Optimised formulations were evaluated in vivo in ten healthy volunteers, who each received, on four separate occasions, the immediate release, small intestinal release and colonic release formulations (each equivalent to 150mg ranitidine), and an intravenous injection of ranitidine (equivalent to 50mg ranitidine). Blood samples were collected and assessed for ranitidine concentration, and radiolabelled placebo pellets were co-administered with the coated ranitidine pellets to monitor their gastrointestinal transit using a gamma camera. Ranitidine was rapidly released and absorbed from the immediate release formulation, whereas the enteric formulation (10% coat weight gain) delayed drug release until some or all of the pellets had emptied into the small intestine. The amylose-ethylcellulose coated formulation (coat ratio 1:3, coat weight gain 25%) retarded ranitidine release until the pellets had reached the colon. The mean absolute bioavailability of ranitidine from the immediate release, small intestinal release and colonic release formulations were 50.6, 46.1 and 5.5%, respectively. These data are in general agreement to those obtained from a previous regional intubation study. The present study therefore demonstrates the practical potential of utilising a non-invasive, formulation-based approach to assess drug absorption from different regions of the human gastrointestinal tract.

  16. Development of In Vitro-In Vivo Correlation/Relationship Modeling Approaches for Immediate Release Formulations Using Compartmental Dynamic Dissolution Data from “Golem”: A Novel Apparatus

    Directory of Open Access Journals (Sweden)

    Martin Čulen

    2015-01-01

    Full Text Available Different batches of atorvastatin, represented by two immediate release formulation designs, were studied using a novel dynamic dissolution apparatus, simulating stomach and small intestine. A universal dissolution method was employed which simulated the physiology of human gastrointestinal tract, including the precise chyme transit behavior and biorelevant conditions. The multicompartmental dissolution data allowed direct observation and qualitative discrimination of the differences resulting from highly pH dependent dissolution behavior of the tested batches. Further evaluation of results was performed using IVIVC/IVIVR development. While satisfactory correlation could not be achieved using a conventional deconvolution based-model, promising results were obtained through the use of a nonconventional approach exploiting the complex compartmental dissolution data.

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

    Science.gov (United States)

    de Azevedo, Mariangela de Burgos M; Tasic, Ljubica; Fattori, Juliana; Rodrigues, Fábio HS; Cantos, Fabiana C; Ribeiro, Leandro P; de Paula, Vanice; Ianzer, Danielle; Santos, Robson AS

    2011-01-01

    Captopril (CAP) was the first angiotensin I-converting enzyme (ACE) inhibitor to be developed and is widely used in hypertension treatment. On the other hand, cyclodextrins (CDs) are cyclic oligosaccharides whose cone-shaped cavity allows formation of noncovalent inclusion complexes with appropriately sized guest molecules, thus modifying guest physical, chemical, and biological properties. Herein, the physicochemical characterization and in vivo ACE inhibition evaluation of seven CAP/CD complexes are reported. The inclusion complexes were prepared by spray-drying, freeze-drying, kneading, or lyophilization methods and characterized by nuclear magnetic resonance, Fourier-transformed infrared spectroscopy, X-ray diffraction, differential scanning calorimetry, and scanning electron microscopy techniques. In vivo assays compared CAP and CAP/CD complex administration (0.5 mg kg−1 or 0.09 mg kg−1, n = 4–7) to evaluate the ACE inhibition by continuous infusion of angiotensin I (30 ng 50 μL−1 min−1) in conscious Wistar rats. The physicochemical analysis demonstrated complete amorphization and complexation between CAP and CDs, indicating the substitution of water molecules inside the CD cavity with CAP. During the infusion of angiotensin I, the administration of all CAP/CD complexes induced a reduction in mean arterial pressure similar to that 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. PMID:21720512

  18. Development and Characterization of Sodium Hyaluronate Microparticle-Based Sustained Release Formulation of Recombinant Human Growth Hormone Prepared by Spray-Drying.

    Science.gov (United States)

    Kim, Sun J; Kim, Chan W

    2016-02-01

    The purpose of this study was to develop and characterize a sodium hyaluronate microparticle-based sustained release formulation of recombinant human growth hormone (SR-rhGH) prepared by spray-drying. Compared to freeze-drying, spray-dried SR-rhGH showed not only prolonged release profiles but also better particle property and injectability. The results of size-exclusion high-performance liquid chromatography showed that no aggregate was detected, and dimer was just about 2% and also did not increase with increase of inlet temperature up to 150 °C. Meanwhile, the results of reversed-phase high-performance liquid chromatography revealed that related proteins increased slightly from 4.6% at 100 °C to 6.3% at 150 °C. Thermal mapping test proved that product temperature did not become high to cause protein degradation during spray-drying because thermal energy was used for the evaporation of surface moisture of droplets. The structural characterization by peptide mapping, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and circular dichroism revealed that the primary, secondary, and tertiary structures of rhGH in SR-rhGH were highly comparable to those of reference somatropin materials. The biological characterization by rat weight gain and cell proliferation assays provided that bioactivity of SR-rhGH was equivalent to that of native hGH. These data establish that spray-dried SR-rhGH is highly stable by preserving intact rhGH and hyaluronate microparticle-based formulation by spray-drying can be an alternative delivery system for proteins.

  19. Evaluation of a single-dose, extended-release epidural morphine formulation for pain control after lumbar spine surgery.

    Science.gov (United States)

    Vineyard, Joseph C; Toohey, John S; Neidre, Arvo; Fogel, Guy; Joyner, Robert

    2014-01-01

    DepoDur, an extended-release epidural morphine, has been used effectively for postoperative pain control following many orthopaedic and general surgery procedures and has provided prolonged analgesia when compared with Duramorph. The goal of this article was to compare the safety and analgesic efficacy of DepoDur versus Duramorph after lumbar spine surgery. A prospective, randomized, double-blind clinical study was completed at a single extended-stay ambulatory surgery center. All patients over 18 undergoing posterior lumbar spine fusions were considered for the study. Sixty patients were randomly assigned to a control or treatment group. The control group received DepoDur before surgery, while the treatment group received Duramorph. Although results show no significant differences between the two groups in postoperative visual analog pain scale scores, use of pain medication, and adverse events, subjects receiving DepoDur were less likely to receive Naloxone and oxygen supplementation, experience nausea or fever, and were more likely to experience hypotension. DepoDur proved to be safe and effective, offering similar prolonged analgesic activity when compared with Duramorph.

  20. Effects of food and alcohol on the pharmacokinetics of an oral, extended-release formulation of hydrocodone in healthy volunteers

    Directory of Open Access Journals (Sweden)

    Farr SJ

    2015-01-01

    Full Text Available Stephen J Farr,1 Cynthia Y Robinson,1 Christopher M Rubino2,3 1Zogenix, Inc., Emeryville, CA, 2Institute for Clinical Pharmacodynamics, Latham, NY, 3School of Pharmacy and Pharmaceutical Sciences, The State University of New York, University at Buffalo, Buffalo, NY, USA Background: The purpose of this study was to evaluate the pharmacokinetics, bioavailability, and safety of oral extended-release hydrocodone (HC-ER when administered with food or alcohol. Methods: Two single-center, open-label, randomized, crossover studies were conducted in healthy volunteers. In a two-period food-interaction study, 12 subjects received HC-ER 20 mg after an overnight fast and a high-fat meal. In a three-period alcohol-interaction study, 30 naltrexone-blocked subjects received HC-ER 50 mg with a 0%, 20%, or 40% alcohol/orange juice solution after an overnight fast. Pharmacokinetic parameters were derived from plasma concentrations of hydrocodone and its metabolites. Results: Exposure to hydrocodone after HC-ER 20 mg was similar in the fed and fasted states, as assessed by area under the plasma concentration versus time curve from time of dosing to time of last detectable concentration (AUC0–t; 316.14 versus 311.94 ng · h/mL; relative bioavailability (Frel was 101.74%. Differences (fed versus fasted in hydrocodone mean maximum plasma concentration (Cmax; 28.86 versus 22.74 ng/mL and median time to Cmax (tmax; 6 versus 8 hours were not clinically significant. Administration of 20% alcohol with HC-ER 50 mg did not increase systemic exposure relative to 0% alcohol (AUC0–t 878 versus 832 ng · h/mL; Frel 105% or result in clinically meaningful changes in Cmax (51.8 versus 46.3 ng/mL or tmax (5.44 versus 6.16 hours. Administration with 40% alcohol increased AUC0–t (1,008 ng · h/mL versus 832 ng · h/mL; Frel 120% and Cmax (109 versus 46.3 ng/mL, and shortened tmax (2.43 versus 6.16 hours. Adverse events occurred in 10.0%, 24.1%, and 66.7% of subjects after 0

  1. Model-Based Dose Selection for Intravaginal Ring Formulations Releasing Anastrozole and Levonorgestrel Intended for the Treatment of Endometriosis Symptoms.

    Science.gov (United States)

    Reinecke, Isabel; Schultze-Mosgau, Marcus-Hillert; Nave, Rüdiger; Schmitz, Heinz; Ploeger, Bart A

    2017-05-01

    Pharmacokinetics (PK) of anastrozole (ATZ) and levonorgestrel (LNG) released from an intravaginal ring (IVR) intended to treat endometriosis symptoms were characterized, and the exposure-response relationship focusing on the development of large ovarian follicle-like structures was investigated by modeling and simulation to support dose selection for further studies. A population PK analysis and simulations were performed for ATZ and LNG based on clinical phase 1 study data from 66 healthy women. A PK/PD model was developed to predict the probability of a maximum follicle size ≥30 mm and the potential contribution of ATZ beside the known LNG effects. Population PK models for ATZ and LNG were established where the interaction of LNG with sex hormone-binding globulin (SHBG) as well as a stimulating effect of estradiol on SHBG were considered. Furthermore, simulations showed that doses of 40 μg/d LNG combined with 300, 600, or 1050 μg/d ATZ reached anticipated exposure levels for both drugs, facilitating selection of ATZ and LNG doses in the phase 2 dose-finding study. The main driver for the effect on maximum follicle size appears to be unbound LNG exposure. A 50% probability of maximum follicle size ≥30 mm was estimated for 40 μg/d LNG based on the exposure-response analysis. ATZ in the dose range investigated does not increase the risk for ovarian cysts as occurs with LNG at a dose that does not inhibit ovulation. © 2016, The American College of Clinical Pharmacology.

  2. Combination of chondroitinase ABC, glial cell line-derived neurotrophic factor and Nogo A antibody delayed-release microspheres promotes the functional recovery of spinal cord injury.

    Science.gov (United States)

    Zhang, Yu; Gu, Zuchao; Qiu, Guixing; Song, Yueming

    2013-11-01

    Spinal cord injury (SCI) is one of the most devastating injuries for patients. Glial cell line-derived neurotrophic factor (GDNF) is an important neurotrophic factor for the regeneration of the spinal neuraxial bundle, but GDNF would degrade rapidly if the protein was injected into the site of injury; thus, it cannot exert its fullest effects. Therefore, we introduced a delivery system of GDNF, poly(lactide-co-glycolic acid) (PLGA) delayed-release microspheres, in the current study and observed the effect of PLGA-GDNF and the combination of PLGA-GDNF and another 2 agents PLGA-chondroitinase ABC (ChABC) and PLGA-Nogo A antibody in the treatment of SCI rats. Our results showed that PLGA-GDNF and the combination of chABC, GDNF, and Nogo A antibody microspheres could elevate the locomotor scores of SCI rats. The effect of PLGA-GDNF was much better than that of GDNF. The cortical somatosensory evoked potential was also improved by PLGA-GDNF and the combination of chABC, GDNF, and Nogo A antibody microspheres. Our results suggest that PLGA delayed-release microsphere may be a useful and effective tool in delivering protein agents into the injury sites of patients with SCI. This novel combination therapy may provide a new idea in promoting the functional recovery of the damaged spinal cord.

  3. Comparing the pharmacokinetics of doxylamine/pyridoxine delayed-release combination in nonpregnant women of reproductive age and women in the first trimester of pregnancy.

    Science.gov (United States)

    Matok, Ilan; Clark, Shannon; Caritis, Steve; Miodovnik, Menachem; Umans, Jason; Hankins, Gary; Koren, Gideon

    2013-03-01

    Although Diclectin (doxylamine/pyridoxine delayed-released combination) is widely used in Canada, its pharmacokinetics (PK) during pregnancy has never been described. The objective of this study was to compare the PK of doxylamine/pyridoxine delayed-released combination in pregnant versus nonpregnant women. The apparent clearances (CL) of doxylamine and pyridoxal 5'-phosphate (PLP; the active metabolite of vitamin B(6) ) during the first-trimester pregnancy in women who participated in a Diclectin randomized trial were compared with those of healthy, adult, nonpregnant women who participated in a voluntary PK trial. Eighteen nonpregnant women were compared with 50 pregnant women who were treated with Diclectin. There was no difference in the apparent CL of doxylamine in women in their first trimester of pregnancy when compared with nonpregnant women on day 4 (median = 196.7 vs 249.5 mL/h/kg, respectively, P = .065), day 8 (median = 248.4 vs 249.5 mL/h/kg, respectively, P = .82), and day 15 (median = 200.9 vs 249.5 mL/h/kg, respectively, P = .55). No difference was found in the apparent CL of PLP on day 15 (median = 342.3 vs 314.7 mL/h/kg, respectively, P = .92). There was no pregnancy-induced effect in the apparent CL of either doxylamine or PLP in women during the first trimester of pregnancy despite the existence of morning sickness.

  4. Delayed Effects of Remote Limb Ischemic Preconditioning on Maximum Oxygen Consumption, Lactate Release and Pulmonary Function Tests in Athletes and non-Athletes

    Directory of Open Access Journals (Sweden)

    Mahnaz Momeni

    2016-11-01

    Full Text Available Background: Remote Ischemic Preconditioning (RIPC improves exercise performance, and since this phenomenon has two phases, the aim of the current study was to investigate the delayed effects of remote ischemic preconditioning on cardiopulmonary function in athletes and non-athletes. Materials and Methods: 25 male and female students were studied in two main athletes and non-athletes groups. RIPC was induced by using 3 cycles of alternative 5 minutes ischemia and 5 minutes reperfusion at arms of participants. Cardiopulmonary tests were measured before, after and 24 hours after inducing remote ischemic preconditioning. Maximum oxygen consumption (VO2max estimated by using queen steps test. Results: Analysis of data demonstrated that delayed RIPC in non-athletes group caused significant improvement in Forced Expiratory Volume in one second (FEV1 and Maximum Voluntary Ventilation (MVV and noticeable improvement in some other parameters of pulmonary function tests. Moreover, it decreased systolic blood pressure and heart rate and decreased lactate release in both groups especially athletes group but it had no significant effect on VO2max of both groups. Conclusion: Delayed RIPC improves cardiovascular function of athletes and pulmonary function of non-athletes subjects. Thus, it can be considered as a good replacement for doping to improve sports performance of subjects in sports tournaments.

  5. Formulation of polylactide-co-glycolic acid nanospheres for encapsulation and sustained release of poly(ethylene imine-poly(ethylene glycol copolymers complexed to oligonucleotides

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    Wheatley Margaret A

    2009-04-01

    Full Text Available Abstract Antisense oligonucleotides (AOs have been shown to induce dystrophin expression in muscles cells of patients with Duchenne Muscular Dystrophy (DMD and in the mdx mouse, the murine model of DMD. However, ineffective delivery of AOs limits their therapeutic potential. Copolymers of cationic poly(ethylene imine (PEI and non-ionic poly(ethylene glycol (PEG form stable nanoparticles when complexed with AOs, but the positive surface charge on the resultant PEG-PEI-AO nanoparticles limits their biodistribution. We adapted a modified double emulsion procedure for encapsulating PEG-PEI-AO polyplexes into degradable polylactide-co-glycolic acid (PLGA nanospheres. Formulation parameters were varied including PLGA molecular weight, ester end-capping, and sonication energy/volume. Our results showed successful encapsulation of PEG-PEI-AO within PLGA nanospheres with average diameters ranging from 215 to 240 nm. Encapsulation efficiency ranged from 60 to 100%, and zeta potential measurements confirmed shielding of the PEG-PEI-AO cationic charge. Kinetic measurements of 17 kDa PLGA showed a rapid burst release of about 20% of the PEG-PEI-AO, followed by sustained release of up to 65% over three weeks. To evaluate functionality, PEG-PEI-AO polyplexes were loaded into PLGA nanospheres using an AO that is known to induce dystrophin expression in dystrophic mdx mice. Intramuscular injections of this compound into mdx mice resulted in over 300 dystrophin-positive muscle fibers distributed throughout the muscle cross-sections, approximately 3.4 times greater than for injections of AO alone. We conclude that PLGA nanospheres are effective compounds for the sustained release of PEG-PEI-AO polyplexes in skeletal muscle and concomitant expression of dystrophin, and may have translational potential in treating DMD.

  6. Effects of poly lactic-co-glycolic acid-Nogo A antibody delayed-release microspheres on regeneration of injured spinal cord in rats

    Institute of Scientific and Technical Information of China (English)

    Hai Lan; Yueming Song

    2009-01-01

    BACKGROUND: Nogo A antigen is the major inhibiting factor blocking regeneration of the injured spinal cord. Neutralizing Nogo A antigens using Nogo A antibodies may help promote neurite regeneration and nervous function recovery. For successful regeneration, sustained release of the antibody from a biodegradable material loaded with Nogo A antibodies to the injury site is required. OBJECTIVE: To compare the therapeutic effects of poly lactic-co-glycolic acid (PLGA)-Nogo A antibody delayed-release microspheres and Nogo A antibody alone on spinal regeneration in Sprague-Dawley rats with complete transverse injury to the spinal cord.DESIGN, TIME AND SETTING: A randomized, controlled animal trial was performed at the Pharmacological Laboratory of West China Center of Medical Sciences, Sichuan University, between October 2007 and January 2008.MATERIALS: Goat anti-rat Nogo A monoclonal antibody was purchased from Santa, American; goat anti-rat neurofilament 200 monoclonal antibody was from Zhongshan Goldenbridge, Beijing, China; PLGA-Nogo A antibody delayed-release microspheres were provided by the College of Pharmacy, Sichuan University.METHODS: A total of 36 adult female Sprague Dawley rats were used to establish models of completely transected spinal cord injury, at T10. Animals were randomly divided into three groups (n=12): model, Nogo A antibody alone, and Nogo A antibody delayed-release microsphere groups. After transverse injury of the spinal cord, 50 μL normal saline solution, 50 μL normal saline solution containing 50 μ g Nogo A antibody, and 50 μ L normal saline solution containing 50 μg Nogo A antibody microspheres were administered to the respective groups at the injury site. MAIN OUTCOME MEASURES: The expression of Nogo A and neurofilament 200 in injured spinal cord was tested immunohistochemically, and motor function of rats was assessed by Basso-Beattie-Bresnahan (BBB) locomotor rating scale.RESULTS: Four weeks after injury, expression of Nogo A in

  7. 基于BP神经网络的缓释制剂处方质量预测研究%Study on Formulation Quality Forecast of Sustained Release Preparation Based on BP Neural Network

    Institute of Scientific and Technical Information of China (English)

    金玉琴; 周金海; 赵群; 张兴德

    2013-01-01

    缓释制剂的处方优化属于多因素、多水平的复杂优化问题,人工神经网络很适于处理这类复杂的多变量非线性关系。本文在对缓释制剂特性及影响其处方设计质量的重要因素进行细致分析的基础上,应用BP人工神经网络建立缓释制剂处方质量预测模型。研究结果表明,BP神经网络可以有效地进行缓释制剂处方质量预测,是缓释制剂处方优化的有力工具。%Optimization on sustained release preparation formulation is a multi-factor, multi-level complex optimiza-tion problem. Artificial neural network is very suitable for dealing with such complex multivariable nonlinear system. Based on analyzing the characteristics of sustained release preparation and the main influential factors of its quality, this paper focused on building a quality forecast model for sustained release preparation formulation by using BP neural network. The results showed that the BP neural network can effectively forecast the quality of sustained re-lease preparation formulation. It is a powerful optimization tool of sustained release preparation formulation.

  8. Inhibition of Mitochondrial Cytochrome c Release and Suppression of Caspases by Gamma-Tocotrienol Prevent Apoptosis and Delay Aging in Stress-Induced Premature Senescence of Skin Fibroblasts

    Directory of Open Access Journals (Sweden)

    Suzana Makpol

    2012-01-01

    Full Text Available In this study, we determined the molecular mechanism of γ-tocotrienol (GTT in preventing cellular aging by focusing on its anti-apoptotic effect in stress-induced premature senescence (SIPS model of human diploid fibroblasts (HDFs. Results obtained showed that SIPS exhibited senescent-phenotypic characteristic, increased expression of senescence-associated β-galactosidase (SA β-gal and promoted G0/G1 cell cycle arrest accompanied by shortening of telomere length with decreased telomerase activity. Both SIPS and senescent HDFs shared similar apoptotic changes such as increased Annexin V-FITC positive cells, increased cytochrome c release and increased activation of caspase-9 and caspase-3 (P<0.05. GTT treatment resulted in a significant reduction of Annexin V-FITC positive cells, inhibited cytochrome c release and decreased activation of caspase-9 and caspase-3 (P<0.05. Gene expression analysis showed that GTT treatment down regulated BAX mRNA, up-regulated BCL2A1 mRNA and decreased the ratio of Bax/Bcl-2 protein expression (P<0.05 in SIPS. These findings suggested that GTT inhibits apoptosis by modulating the upstream apoptosis cascade, causing the inhibition of cytochrome c release from the mitochondria with concomitant suppression of caspase-9 and caspase-3 activation. In conclusion, GTT delays cellular senescence of human diploid fibroblasts through the inhibition of intrinsic mitochondria-mediated pathway which involved the regulation of pro- and anti-apoptotic genes and proteins.

  9. Antiplatelet Effect Durability of a Novel, 24-Hour, Extended-Release Prescription Formulation of Acetylsalicylic Acid in Patients With Type 2 Diabetes Mellitus.

    Science.gov (United States)

    Gurbel, Paul A; Bliden, Kevin P; Chaudhary, Rahul; Patrick, Jeff; Liu, Fang; Chen, Gailing; McLeod, Christopher; Tantry, Udaya S

    2016-12-15

    High platelet reactivity and high platelet turnover have been implicated in incomplete platelet inhibition during immediate-release acetylsalicylic acid therapy in patients with type 2 diabetes mellitus (DM). An extended-release acetylsalicylic acid (ER-ASA; Durlaza) formulation was developed to provide 24-hour antithrombotic effects with once-daily dosing. The objective of the study was to evaluate the antiplatelet effects of ER-ASA in patients with DM. In this open-label, single-center study, patients with DM (n = 40) and multiple cardiovascular risk factors received ER-ASA 162.5 mg/day for 14 ± 4 days. Multiple platelet function tests, serum and urinary thromboxane B2 metabolites, prostacyclin metabolite, and high-sensitive C-reactive protein levels were assessed at 1, 12, 16, and 24 hours post-dose. Patients with high platelet turnover and/or high platelet reactivity were treated with ER-ASA 325 mg/day for 14 ± 4 days, and laboratory analyses were repeated. All patients responded to ER-ASA 162.5 mg/day as measured by arachidonic acid-induced aggregation, and there was no loss of the platelet inhibitory effect of ER-ASA 162.5 mg/day over 24 hours post-dose (p = not significant). The antiplatelet effect was sustained over 24 hours for all platelet function measurements. Mean 1- to 24-hour serum thromboxane B2 levels were low with both doses and were lower with ER-ASA 325 mg/day compared with 162.5 mg/day therapy (p = 0.002). In conclusion, ER-ASA 162.5 mg daily dose provided sustained antiplatelet effects over 24 hours in patients with type 2 DM and multiple cardiovascular risk factors and had a favorable tolerability profile.

  10. The extended-release formulation of quetiapine fumarate (quetiapine XR) adjunctive treatment in partially responsive generalized anxiety disorder (GAD): An open label naturalistic study.

    Science.gov (United States)

    Gabriel, A

    2011-01-01

    To assess the effect of adjunctive treatment with extended-release formulation of quetiapine fumarate (quetiapine XR) to other antidepressants in the treatment of partially responsive, poorly functioning patients with generalized anxiety disorder was assessed. Twenty four consenting adult outpatients with confirmed DSM-IV diagnosis of generalized disorder were identified. All patients failed at least one 8-week treatment trial with SSRI or SNRI antidepressant. All were treated with quetiapine XR as an add on treatment to citalopram or vanlafaxine antidepressant for at least 12 weeks. The primary efficacy measure was the Clinical Global Impression Scale (CGI-S). Other scales included; the Hamilton Anxiety Scale (HAM-A) scale, Sheehan Disability Scale, and the Abnormal Involuntary Movement Scale (AIMS). Baseline measures prior to adding quetiapine XR were compared to those at 4, 8 and 12 weeks with the adjunctive treatment. Twenty three patients completed the trial. There was significant rapid resolution of the anxiety symptoms in all effectiveness measures, including the symptoms of anxiety as shown by changes from baseline in HAM-A, and CGI at four weeks. Improvement was maintained to week twelve. Impairments in work, social, and home responsibilities were also reduced significantly, and there were no significant changes in weight at 12 weeks. Patients tolerated the adjunctive treatment well. Quetiapine XR may have anxiolytic properties and could be used effectively as adjunctive treatment with SSRIs in GAD patients with partial response to SSRs or SNRISs. However double blind randomized trials are needed to support these results.

  11. Chemo-hormone therapy of non-well-differentiated endocrine tumours from different anatomic sites with cisplatinum, etoposide and slow release lanreotide formulation

    Science.gov (United States)

    Correale, P; Sciandivasci, A; Intrivici, C; Pascucci, A; Del Vecchio, M T; Marsili, S; Savelli, V; Voltolini, L; Di Bisceglie, M; Guarnieri, A; Gotti, G; Francini, G

    2007-01-01

    We report the results of a phase II trial in patients with metastatic endocrine tumours from different sites, which aimed to evaluate the anti-tumour activity and toxicity of a cisplatinum and etoposide regimen administered in combination with the somatostatin agonist lanreotide given in slow release formulation. Between January 1999 and November 2003, 27 patients with histological diagnoses of endocrine tumours with different degrees of differentiation, excluding well differentiated carcinoid neoplasms, received intravenous (i.v.) administration of cisplatinum (30 mg m−2) and etoposide (100 mg m−2) on days 1–3 and intramuscular administration of 60 mg lanreotide on day 1, in a 21-day cycle. All of the patients were evaluable for toxicity and response. The treatment was very well tolerated as no grade 4 toxicity was observed. Four patients achieved a complete response, six a partial response, 12 experienced disease stabilisation and five disease progression. The average time to progression and to survival were 9 and 24 months respectively. These results suggest that this chemo-hormone therapy regimen is well tolerated and active in patients with non-well differentiated endocrine tumours. PMID:17437022

  12. Management of dyslipidemias with fibrates, alone and in combination with statins: role of delayed-release fenofibric acid

    Directory of Open Access Journals (Sweden)

    Elisavet Moutzouri

    2010-06-01

    Full Text Available Elisavet Moutzouri, Anastazia Kei, Moses S Elisaf, Haralampos J MilionisDepartment of Internal Medicine, School of Medicine, University of Ioannina, Ioannina, GreeceAbstract: Cardiovascular disease (CVD represents the leading cause of mortality worldwide. Lifestyle modifications, along with low-density lipoprotein cholesterol (LDL-C reduction, remain the highest priorities in CVD risk management. Among lipid-lowering agents, statins are most effective in LDL-C reduction and have demonstrated incremental benefits in CVD risk reduction. However, in light of the residual CVD risk, even after LDL-C targets are achieved, there is an unmet clinical need for additional measures. Fibrates are well known for their beneficial effects in triglycerides, high-density lipoprotein cholesterol (HDL-C, and LDL-C subspecies modulation. Fenofibrate is the most commonly used fibric acid derivative, exerts beneficial effects in several lipid and nonlipid parameters, and is considered the most suitable fibrate to combine with a statin. However, in clinical practice this combination raises concerns about safety. ABT-335 (fenofibric acid, Trilipix® is the newest formulation designed to overcome the drawbacks of older fibrates, particularly in terms of pharmacokinetic properties. It has been extensively evaluated both as monotherapy and in combination with atorvastatin, rosuvastatin, and simvastatin in a large number of patients with mixed dyslipidemia for up to 2 years and appears to be a safe and effective option in the management of dyslipidemia.Keywords: atherogenic dyslipidemia, cardiovascular disease prevention, lipid-lowering treatment, fenofibric acid, statins

  13. Management of dyslipidemias with fibrates, alone and in combination with statins: role of delayed-release fenofibric acid.

    Science.gov (United States)

    Moutzouri, Elisavet; Kei, Anastazia; Elisaf, Moses S; Milionis, Haralampos J

    2010-08-09

    Cardiovascular disease (CVD) represents the leading cause of mortality worldwide. Lifestyle modifications, along with low-density lipoprotein cholesterol (LDL-C) reduction, remain the highest priorities in CVD risk management. Among lipid-lowering agents, statins are most effective in LDL-C reduction and have demonstrated incremental benefits in CVD risk reduction. However, in light of the residual CVD risk, even after LDL-C targets are achieved, there is an unmet clinical need for additional measures. Fibrates are well known for their beneficial effects in triglycerides, high-density lipoprotein cholesterol (HDL-C), and LDL-C subspecies modulation. Fenofibrate is the most commonly used fibric acid derivative, exerts beneficial effects in several lipid and nonlipid parameters, and is considered the most suitable fibrate to combine with a statin. However, in clinical practice this combination raises concerns about safety. ABT-335 (fenofibric acid, Trilipix) is the newest formulation designed to overcome the drawbacks of older fibrates, particularly in terms of pharmacokinetic properties. It has been extensively evaluated both as monotherapy and in combination with atorvastatin, rosuvastatin, and simvastatin in a large number of patients with mixed dyslipidemia for up to 2 years and appears to be a safe and effective option in the management of dyslipidemia.

  14. Development of a Physiologically Relevant Population Pharmacokinetic in Vitro-in Vivo Correlation Approach for Designing Extended-Release Oral Dosage Formulation.

    Science.gov (United States)

    Kim, Tae Hwan; Shin, Soyoung; Bulitta, Jürgen B; Youn, Yu Seok; Yoo, Sun Dong; Shin, Beom Soo

    2017-01-03

    Establishing a level A in vitro-in vivo correlation (IVIVC) for a drug with complex absorption kinetics is challenging. The objective of the present study was to develop an IVIVC approach based on population pharmacokinetic (POP-PK) modeling that incorporated physiologically relevant absorption kinetics. To prepare three extended release (ER) tablets of loxoprofen, three types of hydroxypropyl methylcellulose (HPMC 100, 4000, and 15000 cps) were used as drug release modifiers, while lactose and magnesium stearate were used as the diluent and lubricant, respectively. An in vitro dissolution test in various pH conditions showed that loxoprofen dissolution was faster at higher pH. The in vivo pharmacokinetics of loxoprofen was assessed following oral administration of the different loxoprofen formulations to Beagle dogs (n = 22 in total). Secondary peaks or shoulders were observed in many of the individual plasma concentration vs time profiles after ER tablet administration, which may result from secondary absorption in the intestine due to a dissolution rate increase under intestinal pH compared to that observed at stomach pH. In addition, in vivo oral bioavailability was found to decrease with prolonged drug dissolution, indicating site-specific absorption. Based on the in vitro dissolution and in vivo absorption data, a POP-PK IVIVC model was developed using S-ADAPT software. pH-dependent biphasic dissolution kinetics, described using modified Michaelis-Menten kinetics with varying Vmax, and site-specific absorption, modeled using a changeable absorbed fraction parameter, were applied to the POP-PK IVIVC model. To experimentally determine the biphasic dissolution profiles of the ER tablets, another in vitro dissolution test was conducted by switching dissolution medium pH based on an in vivo estimate of gastric emptying time. The model estimated, using linear regression, that in vivo initial maximum dissolution rate (Vmax(0)in vivo) was highly correlated (r(2) > 0

  15. Effectiveness and safety of a long-acting, once-daily, two-phase release formulation of methylphenidate (Ritalin ® LA) in school children under daily practice conditions.

    Science.gov (United States)

    Haertling, Fabian; Mueller, Beate; Bilke-Hentsch, Oliver

    2015-06-01

    Long-acting (LA) preparations of methylphenidate allow for once-daily dosing; however, pharmacokinetics may vary and depend on food intake. The objective was to evaluate effectiveness of a two-phase release formulation (Ritalin(®) LA) under daily practice conditions. This was a prospective, multicenter, observational study in Germany. Eligibility and dosing were determined by the physician based on the drug label. Outcomes included changes over 3 months of treatment in assessments of effect duration, clinical global impression (CGI), and quality of life (ILK). In 101 sites, 262 patients (197 boys, 63 girls, and two unknown) with a mean age of 10.9 years were enrolled; 50 were treated for the first time; 212 switched medication to Ritalin(®) LA. After 3 months, CGI improved in 59.4 % of patients, and well-being overall was rated as good by 61.0 % of parents and 63.7 % of children. Based on parents' assessment, the proportion of children suffering from strong disease burden decreased from 40.7 to 15.1 %. In 123 insufficient responders to previous ADHD medications, benefit from Ritalin(®) LA was above average and effect duration was significantly prolonged as compared to pretreatment. Overall, 28 patients (10.7 %) had treatment-related adverse events with one case being serious; 23 patients (8.8 %) discontinued therapy, 7 (2.7 %) due to poor treatment response; and 212 patients (81 %) continued treatment beyond the study. In line with clinical trial data, Ritalin(®) LA provides significant benefit also under routine practice conditions.

  16. Zegerid--immediate-release omeprazole.

    Science.gov (United States)

    2005-04-11

    The FDA has approved marketing of Zegerid powder for oral suspension (Santarus), an immediate-release formulation of the proton-pump inhibitor (PPI) omeprazole (Prilosec, and others). All other oral PPIs are delayed-release, enteric-coated formulations designed to prevent degradation of the drug by gastric acid. Each 20- or 40-mg packet of Zegerid contains 1680 mg sodium bicarbonate, which protects the drug from gastric acid degradation. A dose of Zegerid contains 460 mg of sodium, which may be excessive for some patients. Zegerid is the first oral PPI to be approved by the FDA for reduction of risk of upper GI bleeding in critically ill patients. The drug may be useful for patients who are unable to swallow and have nasogastric (NG) tubes in place. Zegerid cost $70.00 for 14 days' treatment, compared to less than $10 for 14 tablets of Prilosec OTC.

  17. Assessing the Subjective and Physiological Effects of Intranasally Administered Crushed Extended-Release Morphine Formulations with and without a Sequestered Naltrexone Core in Recreational Opioid Users

    Directory of Open Access Journals (Sweden)

    Beatrice Setnik

    2013-01-01

    Full Text Available OBJECTIVE: To evaluate the pharmacodynamic (PD effects of morphine sulfate and naltrexone hydrochloride extended-release (MSN capsules compared with controlled-release morphine sulfate (MS and placebo when crushed and administered intranasally.

  18. Delayed-release oral suspension of omeprazole for the treatment of erosive esophagitis and gastroesophageal reflux disease in pediatric patients: a review

    Directory of Open Access Journals (Sweden)

    Alice Monzani

    2010-03-01

    Full Text Available Alice Monzani, Giuseppina Oderda1Department of Pediatrics, Università del Piemonte Orientale, Novara, ItalyAbstract: Omeprazole is a proton-pump inhibitor indicated for gastroesophageal reflux disease and erosive esophagitis treatment in children. The aim of this review was to evaluate the efficacy of delayed-release oral suspension of omeprazole in childhood esophagitis, in terms of symptom relief, reduction in reflux index and/or intragastric acidity, and endoscopic and/or histological healing. We systematically searched PubMed, Cochrane and EMBASE (1990 to 2009 and identified 59 potentially relevant articles, but only 12 articles were suitable to be included in our analysis. All the studies evaluated symptom relief and reported a median relief rate of 80.4% (range 35%–100%. Five studies reported a significant reduction of the esophageal reflux index within normal limits (<7% in all children, and 4 studies a significant reduction of intra-gastric acidity. The endoscopic healing rate, reported by 9 studies, was 84% after 8-week treatment and 95% after 12-week treatment, the latter being significantly higher than the histological healing rate (49%. In conclusion, omeprazole given at a dose ranging from 0.3 to 3.5 mg/kg once daily (median 1 mg/kg once daily for at least 12 weeks is highly effective in childhood esophagitis.Keywords: proton pump inhibitors, children, ranitidine, H2-blockers

  19. Preparation of sustained release matrix pellets by melt agglomeration in the fluidized bed: influence of formulation variables and modelling of agglomerate growth.

    Science.gov (United States)

    Pauli-Bruns, Anette; Knop, Klaus; Lippold, Bernhard C

    2010-03-01

    The one-step preparation of sustained release matrix pellets, using a melting procedure in a fluidized bed apparatus, was tested in a 2(3) full factorial design of experiments, using microcrystalline wax as lipophilic binder, theophylline as model drug and talc as additional matrix forming agent. The three influence parameters were (A) size of binder particles, (B) fraction of theophylline in solid particles and (C) fraction of microcrystalline wax in formulation. The response variables were agglomerate size and size distribution, dissolution time, agglomerate crush resistance, sphericity, yield and porosity. Nearly spherical pellets comprising a smooth, closed surface could be obtained with the used method, exhibiting the hollow core typical for the immersion and layering mechanism. The reproducibility was very good concerning all responses. The size of agglomerates is proportional to the size of the binder particles, which serve as cores for pellet formation in the molten state in the fluidized bed. Additionally, the agglomerate size is influenced by the volume of the solid particles in relation to the binder particles, with more solid particles leading to larger agglomerates and vice versa. Dissolution times vary in a very wide range, resulting from the interplay between amount of drug in relation to the meltable matrix substance microcrystalline wax and the non-meltable matrix substance talc. The change of binder particle size does not lead to a structural change of the matrix; both dissolution times and porosity are not significantly altered. Agglomerate crush resistance is low due to the hollow core of the pellets. However, it is significantly increased if the volume fraction of microcrystalline wax in the matrix is high, which means that the matrix is mechanically better stabilized. A theoretical model has been established to quantitatively explain agglomerate growth and very good accordance of the full particle size distributions between predicted and

  20. Biphasic drug absorption from the epidural space of the dog may limit the utility of a slow release medium molecular weight hyaluronic acid-lidocaine ionic complex formulation.

    Science.gov (United States)

    Doherty, M M; Hughes, P J; Charman, S A; Brock, K V; Korszniak, N V; Charman, W N

    1996-12-01

    Previous epidural studies conducted in rabbits have described a viscous lidocaine-hyaluronate formulation (L-HA) that prolonged the duration of sensory blockade twofold and decreased the rate of drug absorption fourfold relative to a solution formulation. As further evaluation of the L-HA formulation required studies in a larger animal that more closely reflected the characteristic absorption kinetics observed in humans, a conscious dog model was used to functionally and kinetically evaluate the viscous formulation relative to lidocaine solution. In terms of the measured pharmacodynamic end point (loss of weight-bearing ability in hind legs), epidural administration of the L-HA formulation did not prolong the duration of action relative to lidocaine solution in spite of a markedly altered pharmacokinetic profile. For example, administration of L-HA reduced the mean plasma lidocaine Cmax value approximately 50% and increased the Tmax value approximately fivefold relative to lidocaine solution. However, the viscous L-HA formulation did cause a significant prolongation in the latency of onset (P lidocaine solution. The dog exhibited "flip-flop" pharmacokinetics and absorption was biphasic after epidural administration of lidocaine solution (apparent t1/2 of the fast and slow absorption phases were 4 min and 131 min, respectively). The L-HA formulation markedly altered the absorption kinetics such that a single, slow absorption phase was evident (apparent t1/2 of 56 min), although this rate was more rapid than the slow phase observed after lidocaine solution. It is possible that the inability of the hyaluronate-based formulation to further reduce the magnitude of the slow absorption phase resulted in the failure to prolong the duration of action. These data highlight the need to carefully consider the absorption kinetics and pharmacokinetic characteristics of the animal models chosen to evaluate new formulation of epidurally administered local anesthetics.

  1. Formulation development, optimization and study on drug release kinetics of Eudragit® L100-HPMC E15 LV mixed film-coated colon-targeted Mesalamine tablets

    Directory of Open Access Journals (Sweden)

    A Maria John Newton

    2012-01-01

    Full Text Available The study was designed to evaluate the in vitro dissolution characteristics of pH-sensitive polymer - HPMC E 15 LV-coated tablets - in various simulated fluids (pH range 1.2, 6, 7.2. The Mesalamine tablets were fabricated by mixing the drug with microcrystalline cellulose and other ingredients. The fabricated Mesalamine tablets were coated with Eudragit L100 polymer and HPMC E 15 LV. The fluctuation in colonic pH conditions during inflammatory bowel disease and the nature of less fluid content in the colon may limit the expected drug release in the colon. Addition of HPMC E 15 LV may control this problem by hydrophilic nature and excellent film-forming characteristics like ductility and elasticity. The different batches of Mesalamine tablets (FM1-FM5 were coated with increasing concentration of Eudragit L100 and HPMC E 15 LV. The coating was given up to 8% TWG(Total weight gain of the uncoated tablet. Drug release studies were conducted in different pH conditions in the presence of rat ceaecal contents. The different buffer conditions were chosen to mimic the pH changes in the terminal part of the ileum as well as in the colon. The drug release profile was analyzed for colon-targeting performance in vitro. The release profile of the tablets indicates that the drug release was retarded in the tablet by film coating. The addition of HPMC E 15 LV ensures the channels for allowing colonic fluids to penetrate into the core and subsequent drug release at the target site. The kinetics of the drug release also evaluated the release pattern that was best fitted with Higuchian release. The results of the mechanism of release revealed that drug release was found to be a complex one with diffusion, erosion and swelling.

  2. Sex differences in the pharmacokinetics and bioequivalence of the delayed-release combination of doxylamine succinate-pyridoxine hydrochloride; implications for pharmacotherapy in pregnancy.

    Science.gov (United States)

    Koren, Gideon; Vranderick, Manon; Gill, Simerpal K; Macleod, Stuart

    2013-12-01

    Most bioequivalence (BE) studies are conducted in males with the assumption that variability in pharmacokinetics is similar between the sexes. The purpose of this single-center, reference replicate study was to determine the effect of sex on the pharmacokinetics and BE of doxylamine-pyridoxine 10 mg-10 mg delayed-release tablets. Healthy males (n = 12) and non-pregnant females (n = 12) were administered two tablets, and blood sampling was conducted from 1 hour pre-dose until 72 hours post-dose. After 21 days, dose administration and blood sampling were re-conducted. All analytes were measured using liquid chromatography-tandem mass-spectrometry. Pharmacokinetic parameters were calculated for each study period using standard, non-compartmental methods, and differences were assessed using ANOVA. BE testing was conducted using the relative 90% confidence interval for the AUC0-t for each analyte. Females had significantly larger AUC0-t for doxylamine, 1,550 ng h/mL (coefficient of variance [CV = 19%]) versus 1,272 ng h/mL (CV = 21%; P ≤ .05), and pyridoxine, 35 ng h/mL, (CV = 43%) versus 25 ng h/mL (CV = 31%; P ≤ .05) compared to males. A higher Cmax for doxylamine was observed in females, 107 ng/mL (CV = 16%), compared to males, 86 ng/mL (CV = 15%) (P ≤ .05). BE testing did not demonstrate bioequivalence between males and females. Pharmacokinetic differences observed between the sexes have implications for future BE studies using doxylamine-pyridoxine.

  3. Developing Quantitative In Vitro-In Vivo Correlation for Fenofibrate Immediate-Release Formulations With the Biphasic Dissolution-Partition Test Method.

    Science.gov (United States)

    Xu, Hao; Shi, Yi; Vela, Socrates; Marroum, Patrick; Gao, Ping

    2017-06-27

    This study is to evaluate 3 fenofibrate (FEN) formulations including Fournier® 200 mg capsule, Lipidil® 145 mg tablet, and a clinical HME 160 mg tablet by an in vitro biphasic method. Key experimental parameters were evaluated including the selection of biorelevant media, the United States Pharmacopeia IV flow rate, and the United States Pharmacopeia paddle speed. Varying the hydrodynamic condition resulted in a significant impact on FEN concentration time profiles in both aqueous and octanol phases for these formulations. In vivo pharmacokinetic profiles of the HME tablet, the Lipidil tablet, and Fournier capsule under the fasting and low-fat fed states are reported. Their corresponding absorption-time profiles were obtained through deconvolution by the Wagner-Nelson method. When fed state simulated intestinal fluid version 2 was used, the partitioned FEN amount-time profiles in octanol from the 3 formulations under an appropriate hydrodynamic condition exhibited a good agreement with their in vivo absorbed amount-time profiles, permitting a quantitative in vitro-in vivo correlation. When fasted state simulated intestinal fluid version 2 was used, partitioned FEN amounts into octanol from these formulations are significantly lower than those from in vivo data. Although no food effect was observed for both HME and Lipidil tablets, the positive food effect of the Fournier capsules significantly overestimated by the biphasic test. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  4. Assessment of Alcohol-Induced Dose Dumping with a Hydrocodone Bitartrate Extended-Release Tablet Formulated with CIMA® Abuse Deterrence Technology

    OpenAIRE

    Darwish, Mona; Bond, Mary; Yang, Ronghua; Tracewell, William; Robertson, Philmore

    2015-01-01

    Background Greater drug content requirements for extended-release (ER) opioids necessitate greater protection against dose dumping. Hydrocodone ER employs the CIMA® Abuse-Deterrence Technology platform, which provides resistance against rapid release of the active moiety when the tablet is manipulated or taken with alcohol. Objective Assess effects of alcohol on hydrocodone ER pharmacokinetics. Study Design Open-label, crossover (January 25–April 30, 2010). Setting Single center. Participants...

  5. Formulation and in vitro release evaluation of newly synthesized palm kernel oil esters-based nanoemulsion delivery system for 30% ethanolic dried extract derived from local Phyllanthus urinaria for skin antiaging

    Directory of Open Access Journals (Sweden)

    Mahdi ES

    2011-10-01

    Full Text Available Elrashid Saleh Mahdi1, Azmin Mohd Noor1, Mohamed Hameem Sakeena1, Ghassan Z Abdullah1, Muthanna F Abdulkarim1, Munavvar Abdul Sattar2 1Department of Pharmaceutical Technology, 2Department of Physiology, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Pulau Pinang, Malaysia Background: Recently there has been a remarkable surge of interest about natural products and their applications in the cosmetic industry. Topical delivery of antioxidants from natural sources is one of the approaches used to reverse signs of skin aging. The aim of this research was to develop a nanoemulsion cream for topical delivery of 30% ethanolic extract derived from local Phyllanthus urinaria (P. urinaria for skin antiaging. Methods: Palm kernel oil esters (PKOEs-based nanoemulsions were loaded with P. urinaria extract using a spontaneous method and characterized with respect to particle size, zeta potential, and rheological properties. The release profile of the extract was evaluated using in vitro Franz diffusion cells from an artificial membrane and the antioxidant activity of the extract released was evaluated using the 2, 2-diphenyl-1-picrylhydrazyl (DPPH method. Results: Formulation F12 consisted of wt/wt, 0.05% P. urinaria extract, 1% cetyl alcohol, 0.5% glyceryl monostearate, 12% PKOEs, and 27% Tween® 80/Span® 80 (9/1 with a hydrophilic lipophilic balance of 13.9, and a 59.5% phosphate buffer system at pH 7.4. Formulation F36 was comprised of 0.05% P. urinaria extract, 1% cetyl alcohol, 1% glyceryl monostearate, 14% PKOEs, 28% Tween® 80/Span® 80 (9/1 with a hydrophilic lipophilic balance of 13.9, and 56% phosphate buffer system at pH 7.4 with shear thinning and thixotropy. The droplet size of F12 and F36 was 30.74 nm and 35.71 nm, respectively, and their nanosizes were confirmed by transmission electron microscopy images. Thereafter, 51.30% and 51.02% of the loaded extract was released from F12 and F36 through an artificial cellulose membrane

  6. Gastroretentive Drug Delivery System of Levo-Salbutamol Sulphate: Formulation and in vitro Evaluation

    Directory of Open Access Journals (Sweden)

    Kamanashis Das

    2016-03-01

    Full Text Available In order to prepare the sustained release tablet with levo-salbutamol sulphate we have used these excipients methylcellulose, PVPK30, magnesium stearate, talc, isopropyl alcohol, microcrystalline cellulose, lactose, HPMCK100, HPMCK4M. Here our approach was for making the sustained released matrix tablet by two ways, one is to make the tablet granules floating and the second one is by retarding the release of the levo-salbutamol sulphate from the matrix. We have already discussed the relationship with delaying the gastric transit time and the active drug absorption, if the tablet granules are floating in our introduction part. Since the above mentioned excipients are floating in nature so formulations with those excipients are supposed to be floating. We also showed a list of excipients those are used in the preparation of floating tablets. Now the second observation which was the release rate, among the three different formulations (mentioned in the introduction we found different types of release. Since our objective is to prepare a sustained released tablet which will give a prolong release time, in that prospect two among the three formulations were disqualified (though we have not done the kinetic study. We observed desired effect in the formulation-2 during the preparation of experiment.

  7. [A new LH-RH agonist for treatment of prostate cancer, 3-month controlled-release formulation of goserelin acetate (Zoladex LA 10.8 mg depot)--outline of pre-clinical and clinical studies].

    Science.gov (United States)

    Tsukagoshi, Shigeru

    2002-09-01

    Goserelin acetate is a LH-RH agonist developed by AstraZeneca (formerly ICI, UK), and has been used clinically for the treatment of prostate cancer as a 4-week controlled-release formulation (Zoladex 3.6 mg depot). Recently, a new drug (Zoladex LA 10.8 mg depot) with 3-month controlled-release formulation was developed and became commercially available in Japan. In the randomized comparative phase III studies carried out with global bases, single administration of the new drug yielded almost equivalent anti-testosterone effect and the same serum level of the previous 3.6 mg depot formulation in 3-times continuous administration. In these studies, adverse drug reactions, which were mainly due to pharmacological effects of the new drug and minimal, were found in 52.6% (41/78) compared with 54.8% (46/84) with the previous 3.6 mg depot formulation. In the phase III studies, there were no significant differences in average serum testosterone levels between the two formulations at 12 and 13 weeks after administration. In the Japanese late phase II study with untreated patients, castration effect was observed in all 20 cases entered in the trial. In 20 cases in which treatment was switched from 3.6 mg depot to the new formulation, there were no significant changes in serum testosterone levels at castration level of the untreated patients, 90% (18/20) responded to the treatment, and normalization of PSA level was found in 75.0% (15/20). The adverse drug reactions were mainly increased triglyceride level and hot flushes. In the retrospective evaluation of untreated patients in this trial and the post-marketing clinical trial data for 3.6 mg depot, it was concluded that the new drug had almost the same efficacy and safety profile as 3.6 mg depot in Japanese people. These results indicate that Zoladex LA 10.8 mg depot has the same efficacy and safety as 3.6 mg depot with administration every three months, the burden of injection of LH-RH agonist can be reduced. This new

  8. Effect of the formulation parameters on the encapsulation efficiency and release behavior of p-aminobenzoic acid-loaded ethylcellulose microspheres

    Directory of Open Access Journals (Sweden)

    Mouffok Meryem

    2016-01-01

    Full Text Available In the current study, p-aminobenzoic acid-loaded ethylcellulose microspheres were prepared under various conditions by solvent evaporation method (o/w. This preparation was carried out with different p-aminobenzoic acid:ethylcellulose (PABA:EC ratios, stirring speed, surfactant nature and concentration in order to investigate their effect on encapsulation efficiency and drug release kinetics. Scanning Electron Microscopy (SEM studies showed spherical microspheres with a porous surface and different structures. The mean diameter of Sauter (d32 of these microparticles is in the range from 47 to 165 μm with PVA and from 793 to 870 μm with Tween 80 by adjusting process parameters. However, the encapsulation efficiency varied from 37.52 to 79.05 % suitable for the adjustment of a p-aminobenzoic acid with pro-longed release. Microspheres were characterized by FTIR, DSC and XRD. The release of cation of p-aminobenzoic acid was performed in simulated gastric medium at pH 1.2 and 37±0.5°C by UV-VIS analysis to estimate its content. The release data were best fitted to Higuchi model with high correlation coefficient (r² and the obtained values of n from Korsmeyer-Peppas showed that the drug release follows the Fickian diffusion mechanism.

  9. Lornoxicam Immediate-Release Tablets: Formulation and Bioequivalence Study in Healthy Mediterranean Volunteers Using a Validated LC-MS/MS Method.

    Science.gov (United States)

    Zaid, Abdel Naser; Mousa, Ayman; Jaradat, Nidal; Bustami, Rana

    2017-02-08

    This study aimed to demonstrate interchangeability between 2 lornoxicam tablet formulations under fasting conditions among Mediterranean Arabs by using a newly validated high-pressure liquid chromatography-tandem mass spectrometry method. A single-oral solid dosage form (8 mg/tablet), randomized, open-label, 2-way crossover study was conducted on 30 healthy male volunteers. Blood samples were collected prior to dosing and over a 24-hour period, and the washout period was 9 days. Statistical comparison of the main pharmacokinetic parameters showed no significant difference between generic and branded products. The point estimates (ratios of geometric mean %) were 90.91, 96.34, and 94.86 for Cmax, AUC0-last , and AUC0-∞ , respectively. The 90% confidence intervals were within the predefined limits of 80.00%-125.00%, as specified by the international guidelines. This study showed that both formulations met the regulatory criteria for bioequivalence.

  10. Formulation Optimization of Sustained-Release Ammonio Methacrylate Copolymer Microspheres. Effects of Log P and Concentration of Polar Cosolvents, and Role of the Drug/Copolymer Ratio

    Directory of Open Access Journals (Sweden)

    Piroska Szabó-Révész

    2011-11-01

    Full Text Available The objectives of this work were the formulation optimization of the preparation process parameters and to evaluate spray-dried sustained-release microspheres using ammonio methacrylate copolymer (AMC as a polymer matrix. The effects of log P and the concentrations of the cosolvents (acetone, methyl ethyl ketone and n-butyl acetate and different drug/copolymer ratios as independent variables on the physicochemical parameters (the W1/O emulsion viscosity, the microsphere production yield, the average particle size, the encapsulation efficiency and the cumulative in vitro drug release as dependent variables were studied. The optimization was carried out on the basis of the 33 factorial design study. The optimization process results showed that addition of polar cosolvents proved effective, linear relationships were observed between the independent and the dependent variables. The best conditions were achieved by microspheres prepared by using a low/medium cosolvent log P, cosolvent concentration of 25–50% v/v and a drug/copolymer ratio of 1:16. The microspheres ensured sustained release with Nernst and Baker-Lonsdale release profiles.

  11. Evaluation of the surface chemistry and drug-polymer interaction of semi-crystalline micro-particles for the development of controlled release formulations.

    Science.gov (United States)

    Mithu, Sadeque H; Haque, Syed N; Chowdhry, Babur Z; Nokhodchi, Ali; Maniruzzaman, Mohammed

    2017-07-01

    This research work explores the surface chemistry and drug-polymer interaction in the manufactured controlled release micro-particles. Isoniazid (INH) was used as a model anti-tubercular drug while Eudragit® S100 (S100), Eudragit® L100-55 based co-processed Acryl EZE (EZE) and Ethylcellulose ECN10 (ECN10) were used as polymeric carriers. INH containing micro-particles were prepared using a mini spray dryer B-290 (Buchi, Switzerland). The drug polymer ratios were optimized at 1:1 and 1:3 to evaluate the effect of polymers on the release of the drug from the micro-particles. Solid state characterization via SEM and particle size analysis of the manufactured micro-particles showed densely aggregated spherical particles with a mean diameter particles. The physico-chemical characterization carried out by using DSC and XRPD showed an increase in the amorphicity of the drug during the spray drying process while the chemical elemental analysis via XPS revealed a strong intermolecular interaction between the amine group of the drug and the carboxyl group of the polymers. As expected, the in vitro dissolution study showed a slow release pattern for the highly water soluble drug INH in acidic media (pH1.2) for the first 2h followed by a burst release upon changing the pH to 6.8. It was concluded that emerging spray drying processing can be used as a valuable tool to encapsulate drug for controlled release dosage forms by means of facilitating a possible drug/polymer interaction as outlined by novel XPS analysis. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Comparative pharmacokinetics of two modified-release oral morphine formulations (Reliadol® and Kapanol®) and an immediate-release morphine tablet (Morfin 'DAK') in healthy volunteers

    DEFF Research Database (Denmark)

    Bochner, F.; Somogyi, A.A.; Danz, C.

    1999-01-01

    , its metabolites morphine-6-glucuronide (M6G) and morphine-3-glucuronide (M3G), after ingestion of Reliadol® (2 x 30 mg capsules) compared with Kapanolo (3 x 20 mg) [Glaxo Wellcome Australia Ltd] and an immediate-release morphine tablet (Morfin 'DAK', 30 mg; Nycomed Denmark A/S). Design and Setting...

  13. 响应面法优化富马酸喹硫平缓释片处方%Optimization of the Formulation of Fumarate Quetiapine Sustained-release Tablets by Response Surface Methodology

    Institute of Scientific and Technical Information of China (English)

    沈艳; 任丽莉; 王丞; 陈建龙; 陈国广

    2012-01-01

    OBJECTIVE:To optimize the formulation of Fumarate quetiapine sustained-release tablets. METHODS:Using comprehensive score of the cumulate release rate behavior as response value, response surface methodology of 3 factors and 3 levels was used to determine the viscosity and dosage of HPMC and the dose of natrium citricum and lactose, and to explore drug release mechanism in vitro. RESULTS: HPMC K15M was selected as framework material, and the dosage of it was 13.5% ; the doses of sodium citrate and lactose were 9.5% and 14%. Sustained-release tablets in vitro release fitted to the Higuchi equation, the release behavior in vitro is diffusion combined with corrosion. CONCLUSION: The optimized preparation process of Fumarate quetiapine sustained-release tablet is stable, feasible and the tablets have sustained-release behavior.%目的:优化富马酸喹硫平缓释片处方.方法:以累积释放度综合评分作为响应值,采用3因素3水平的响应面法,确定富马酸喹硫平缓释片处方中羟丙甲纤维素(HPMC)的黏度、用量与枸橼酸钠、乳糖的用量,并探讨其体外释药机制.结果:骨架材料选择HPMC K15M,考虑到实际操作便利确定其用量为13.5%,枸橼酸钠用量为9.5%,乳糖用量为14%.缓释片体外释放符合Higuchi方程,释药机制为扩散和溶蚀并存的双重机制.结论:筛选所得的富马酸喹硫平缓释片处方工艺稳定可行,有一定的缓释作用.

  14. 壳寡糖-聚乳酸阿霉素胶团体外缓释性能考察%Evaluation of Delayed Release Efficiency in Vitro of Adriamycin Chitosan-Polylactic Acid Polymeric Micelles

    Institute of Scientific and Technical Information of China (English)

    隋璐莹

    2015-01-01

    Objective Evaluate the ef iciency of delayed release in vitro of adriamycin chitosan-polylactic acid polymeric micel es.Methods Hypersound dispersion method to prepare the polymeric micel es. Adriamycin as a model drug was then incorporated into the micel es by dialysis. Evaluate the ef iciency of delayed release of adriamycin chitosan-polylactic acid polymeric micel es by in vitro investigation. Results The CSO-PLA micel es with 5000 molecule weight of PLA loading Adr displayed more sustained-release characteristic.Conclusion The micel es loading Adr displayed sustained-release characteristic in vitro. The CSO-PLA (PLA with molecule weight 5000) micel es loading Adr displayed significant sustained-release characteristic.%目的:考察阿霉素壳寡糖-聚乳酸嫁接物胶团的缓释性能。方法以超声分散法制备嫁接物胶团;以阿霉素为模型药物,透析法制备载药胶团。进行载药胶团体外释放实验,考察壳寡糖-聚乳酸共聚物胶团的缓释性能。结果在壳寡糖-聚乳酸嫁接物中,聚乳酸分子量为5000的两种壳寡糖-聚乳酸嫁接物载药胶团体外释放缓释效果明显。结论壳寡糖-聚乳酸聚合物胶团具有显著的缓释特征。其中聚乳酸分子量为5000的壳寡糖-聚乳酸嫁接物,缓释效果更明显。

  15. An oral multiparticulate, modified-release, hydrocortisone replacement therapy that provides physiological cortisol exposure.

    Science.gov (United States)

    Whitaker, Martin; Debono, Miguel; Huatan, Hiep; Merke, Deborah; Arlt, Wiebke; Ross, Richard J

    2014-04-01

    It is not possible with current hydrocortisone replacement to mimic the diurnal cortisol profile in patients with adrenal insufficiency. Previous attempts with modified-release technology were unsuccessful. Our objective was to develop hydrocortisone formulations that recreate the diurnal cortisol profile using multiparticulate technology. Screening by in vitro dissolution profiles, pharmacokinetic (PK) testing in dexamethasone-suppressed dogs and humans, and comparison with a reference population. Field laboratories and clinical research facility. Formulations were generated using an enteric (delayed release) design configuration with an extended (sustained release) dissolution profile. In vitro dissolution confirmed delayed and sustained hydrocortisone release. However, in dogs and humans, sustained release resulted in reduced bioavailability. A formulation, DIURF-006, was developed that maintained delayed release but omitted the sustained-release functionality. PK characterization of DIURF-006 showed that, despite absence of a sustained-release component, absorption was sufficiently sustained to deliver extended hydrocortisone absorption. In dexamethasone-suppressed volunteers (n = 16) receiving a twice-daily 'toothbrush' regimen (20 mg at 23:00 h and 10 mg at 07:00 h), DIURF-006 gave a similar cortisol profile to physiological cortisol levels: DIURF-006 vs physiological, Geomean AUC 5610 vs 4706 h * nmol/l, Geomean Cmax 665 vs 594 nmol/l and Median Tmax 8·5 h vs clock time 08:12 h for peak cortisol. The relative bioavailability of DIURF-006 vs hydrocortisone was 89%, and cortisol levels increased linearly with doses between 5 and 30 mg. A multiparticulate oral hydrocortisone formulation with only an enteric coat provides delayed and sustained absorption and when given in a 'toothbrush' regimen provides physiological cortisol exposure. © 2013 John Wiley & Sons Ltd.

  16. An oral multi-particulate, modified release, hydrocortisone replacement therapy that provides physiological cortisol exposure

    Science.gov (United States)

    Huatan, Hiep; Merke, Deborah; Arlt, Wiebke; Ross, Richard J.

    2013-01-01

    Objective It is not possible with current hydrocortisone replacement to mimic the diurnal cortisol profile in patients with adrenal insufficiency. Previous attempts with modified release technology were unsuccessful. Our objective was to develop hydrocortisone formulations that recreate the diurnal cortisol profile using multi-particulate technology. Design and Measurements Screening by in-vitro dissolution profiles, pharmacokinetic testing in dexamethasone suppressed dogs and humans, and comparison to a reference population. Setting Field laboratories and clinical research facility. Results Formulations were generated using an enteric (delayed-release) design configuration with an extended (sustained-release) dissolution profile. In-vitro dissolution confirmed delayed and sustained hydrocortisone release. However, in dogs and humans, sustained release resulted in reduced bioavailability. A formulation, DIURF-006, was developed that maintained delayed release but omitted the sustained release functionality. Pharmacokinetic characterisation of DIURF-006 showed that, despite absence of a sustained release component, absorption was sufficiently sustained to deliver extended hydrocortisone absorption. In dexamethasone-suppressed volunteers (n=16) receiving a twice daily ‘toothbrush’ regimen (20mg at 23:00h and 10mg at 07:00h), DIURF-006 gave a similar cortisol profile to physiological cortisol levels: DIURF-006 vs physiological, Geomean AUC 5610 vs 4706 hr*nmol/l, Geomean Cmax 665 vs 594 nmol/l and Median Tmax 8.5h vs clock time 08:12 hours for peak cortisol. The relative bioavailability of DIURF-006 vs hydrocortisone was 89% and cortisol levels increased linearly with doses between 5 and 30mg. Conclusion A multi-particulate oral hydrocortisone formulation with only an enteric coat provides delayed and sustained absorption and when given in a ‘toothbrush’ regimen provides physiological cortisol exposure. PMID:23980724

  17. Experimental design for the formulation and optimization of novel cross-linked oilispheres developed for in vitro site-specific release of Mentha piperita oil.

    Science.gov (United States)

    Sibanda, Wilbert; Pillay, Viness; Danckwerts, Michael P; Viljoen, Alvaro M; van Vuuren, Sandy; Khan, Riaz A

    2004-03-12

    A Plackett-Burman design was employed to develop and optimize a novel crosslinked calcium-aluminum-alginate-pectinate oilisphere complex as a potential system for the in vitro site-specific release of Mentha piperita, an essential oil used for the treatment of irritable bowel syndrome. The physicochemical and textural properties (dependent variables) of this complex were found to be highly sensitive to changes in the concentration of the polymers (0%-1.5% wt/vol), crosslinkers (0%-4% wt/vol), and crosslinking reaction times (0.5-6 hours) (independent variables). Particle size analysis indicated both unimodal and bimodal populations with the highest frequency of 2 mm oilispheres. Oil encapsulation ranged from 6 to 35 mg/100 mg oilispheres. Gravimetric changes of the crosslinked matrix indicated significant ion sequestration and loss in an exponential manner, while matrix erosion followed Higuchi's cube root law. Among the various measured responses, the total fracture energy was the most suitable optimization objective (R2 = 0.88, Durbin-Watson Index = 1.21%, Coefficient of Variation (CV) = 33.21%). The Lagrangian technique produced no significant differences (P > .05) between the experimental and predicted total fracture energy values (0.0150 vs 0.0107 J). Artificial Neural Networks, as an alternative predictive tool of the total fracture energy, was highly accurate (final mean square error of optimal network epoch approximately 0.02). Fused-coated optimized oilispheres produced a 4-hour lag phase followed by zero-order kinetics (n > 0.99), whereby analysis of release data indicated that diffusion (Fickian constant k1 = 0.74 vs relaxation constant k2 = 0.02) was the predominant release mechanism.

  18. Improved cortisol exposure-time profile and outcome in patients with adrenal insufficiency: a prospective randomized trial of a novel hydrocortisone dual-release formulation.

    Science.gov (United States)

    Johannsson, G; Nilsson, A G; Bergthorsdottir, R; Burman, P; Dahlqvist, P; Ekman, B; Engström, B E; Olsson, T; Ragnarsson, O; Ryberg, M; Wahlberg, J; Biller, B M K; Monson, J P; Stewart, P M; Lennernäs, H; Skrtic, S

    2012-02-01

    Patients with treated adrenal insufficiency (AI) have increased morbidity and mortality rate. Our goal was to improve outcome by developing a once-daily (OD) oral hydrocortisone dual-release tablet with a more physiological exposure-time cortisol profile. The aim was to compare pharmacokinetics and metabolic outcome between OD and the same daily dose of thrice-daily (TID) dose of conventional hydrocortisone tablets. We conducted an open, randomized, two-period, 12-wk crossover multicenter trial with a 24-wk extension at five university hospital centers. The trial enrolled 64 adults with primary AI; 11 had concomitant diabetes mellitus (DM). The same daily dose of hydrocortisone was administered as OD dual-release or TID. We evaluated cortisol pharmacokinetics. Compared with conventional TID, OD provided a sustained serum cortisol profile 0-4 h after the morning intake and reduced the late afternoon and the 24-h cortisol exposure. The mean weight (difference = -0.7 kg, P = 0.005), systolic blood pressure (difference = -5.5 mm Hg, P = 0.0001) and diastolic blood pressure (difference: -2.3 mm Hg; P = 0.03), and glycated hemoglobin (absolute difference = -0.1%, P = 0.0006) were all reduced after OD compared with TID at 12 wk. Compared with TID, a reduction in glycated hemoglobin by 0.6% was observed in patients with concomitant DM during OD (P = 0.004). The OD dual-release tablet provided a more circadian-based serum cortisol profile. Reduced body weight, reduced blood pressure, and improved glucose metabolism were observed during OD treatment. In particular, glucose metabolism improved in patients with concomitant DM.

  19. 对乙酰氨基酚温敏凝胶的处方筛选与体外释放研究%Study on Optimized Formulation and Release of Paracetamol Thermosensitive Gel in Vitro

    Institute of Scientific and Technical Information of China (English)

    王晓辉; 袁园; 张莉; 胡霞; 仲博; 陈莉

    2012-01-01

    目的 筛选对乙酰氨基酚温度敏感型原位凝胶处方组成,并对其体外释药进行研究.方法 以泊洛沙姆407、泊洛沙姆188为考察因素,以胶凝温度为考察指标,分别用多元线性模型、二次多项式模型描述考察指标和因素之间的数学关系,用中心组合设计-效应面法确定最优处方.采用相似因子法对优化处方与传统栓剂进行体外溶出比较.结果 对乙酰氨基酚温度敏感型原位凝胶的最优处方为7.5%药物、21%泊洛沙姆407和18%泊洛沙姆188,胶凝温度为36.2℃.对乙酰氨基酚温敏凝胶与传统栓剂均在45 min内释药达80%,2h内药物基本释放完全,且释药曲线相似(差异因子f1=2.06%,相似因子f2=68.7%).结论 优化的处方具有适宜的胶凝温度且释药符合要求.%Objective To optimize the formulation of paracetamol thermosensitive in situ gel and study the in vitro release of paracetamol from the gel. Methods With the amount of Poloxamer 407 ( P407) , Poloxamer 188 (P188) as independent variables, and gel temperature as an dependent variable, the formulation was optimized. Multilinear and quadratic models were used to estimate the relationship between the dependent and the independent variables and to select the optimal formulation using the central composite design-response surface methodology ( RSM plus CCD). Paracetamol dissolution profiles obtained from the gel were compared with the traditional solid suppository by the similarity factor. Results The optimized formulation of paracetamol thermosensitive gel was 7.5% drug,21% P407 and 18% PI88. Its gelling temperature was at 36. 2 ℃. The accumulative drug release of the thermosensitive gel and the traditional solid suppository was more than 80% in 45 min,and the drug was completely released in 2 h. The dissolution profiles were similar. Conclusion The optimized formulation of paracetamol thermosensitive gel has an appropriate gelatinization temperature and in

  20. Effect of food on the bioavailability of adinazolam from a sustained release formulation: effect of meal timing and lack of dose dumping.

    Science.gov (United States)

    Fleishaker, J C; Phillips, J P; Lau, H S

    1990-11-01

    Food effects on adinazolam absorption from sustained release (SR) adinazolam mesylate tablets were assessed in 28 healthy male volunteers. Subjects received 15 mg SR tablets, 15 mg immediate release tablets, 15 mg oral solution, administered after an overnight fast, and 15 mg SR tablets after a high fat breakfast. Treatments were administered in a crossover design. Plasma adinazolam and N-desmethyladinazolam (NDMAD) concentrations were determined by HPLC. Adinazolam and NDMAD AUC values were unaffected by food. Cmax for SR tablets was increased 33 per cent and 18 per cent for adinazolam and NDMAD, respectively, when administered postprandially. Tmax occurred later in the fed state; no dose dumping was observed. Meal timing effects on adinazolam absorption from SR tablets were assessed in 24 healthy subjects, who received 30 mg SR tablets 1 h before, 0.5 h after, 2 h after a high fat meal, and in the fasted state. Postprandial administration had no effect on AUC, but resulted later and higher adinazolam and NDMAD Cmax. Differences in these values were less than 11 per cent. Administration of SR tablets before meals yielded Cmax and Tmax values which were similar to the fasted state. Results suggest that meal timing does not substantially affect adinazolam absorption from the SR tablet.

  1. Application of Pharmacokinetics and Pharmacodynamics in Product Life Cycle Management. A Case Study with a Carbidopa-Levodopa Extended-Release Formulation.

    Science.gov (United States)

    Modi, Nishit B

    2017-05-01

    Increasing costs in discovering and developing new molecular entities and the continuing debate on limited company pipelines mean that pharmaceutical companies are under significant pressure to maximize the value of approved products. Life cycle management in the context of drug development comprises activities to maximize the effective life of a product. Life cycle approaches can involve new formulations, new routes of delivery, new indications or expansion of the population for whom the product is indicated, or development of combination products. Life cycle management may provide an opportunity to improve upon the current product through enhanced efficacy or reduced side effects and could expand the therapeutic market for the product. Successful life cycle management may include the potential for superior efficacy, improved tolerability, or a better prescriber or patient acceptance. Unlike generic products where bioequivalence to an innovator product may be sufficient for drug approval, life cycle management typically requires a series of studies to characterize the value of the product. This review summarizes key considerations in identifying product candidates that may be suitable for life cycle management and discusses the application of pharmacokinetics and pharmacodynamics in developing new products using a life cycle management approach. Examples and a case study to illustrate how pharmacokinetics and pharmacodynamics contributed to the selection of dosing regimens, demonstration of an improved therapeutic effect, or regulatory approval of an improved product label are presented.

  2. Abuse Potential with Oral Route of Administration of a Hydrocodone Extended-Release Tablet Formulated with Abuse-Deterrence Technology in Nondependent, Recreational Opioid Users

    Science.gov (United States)

    Darwish, Mona; Ma, Yuju; Tracewell, William; Robertson, Philmore; Webster, Lynn R.

    2017-01-01

    Objective. To compare the oral abuse potential of hydrocodone extended-release (ER) tablet developed with CIMA® Abuse-Deterrence Technology with that of hydrocodone immediate release (IR). Design. Randomized, double-blind, placebo-controlled, crossover study. Setting and Patients. One study site in the United States; adult nondependent, recreational opioid users. Methods. After confirming their ability to tolerate and discriminate hydrocodone IR 45 mg from placebo, eligible participants were randomized to receive each of the following oral treatments once: finely crushed placebo, hydrocodone IR 45-mg powder, intact hydrocodone ER 45-mg tablet, and finely crushed hydrocodone ER 45-mg tablet. Primary pharmacodynamic measure was “at the moment” drug liking. Secondary measures included overall drug liking, drug effects (e.g., balance, positive, negative, sedative), pupillometry, pharmacokinetics, and safety. Results. Mean maximum effect (Emax) for “at the moment” drug liking was significantly lower for intact (53.9) and finely crushed hydrocodone ER (66.9) vs. hydrocodone IR (85.2; P < 0.001). Drug liking for intact hydrocodone ER was comparable to placebo (Emax: 53.9 vs. 53.2). Secondary measures were consistent with these results, indicating that positive, negative, and sedative drug effects were diminished with intact and crushed hydrocodone ER tablet vs. hydrocodone IR. The 72-hour plasma concentration-time profile for each treatment mimicked its respective “at the moment” drug-liking-over-time profile. Incidence of adverse events was lower with intact hydrocodone ER (53%) vs. hydrocodone IR (79%) and finely crushed hydrocodone ER (73%). Conclusions. The oral abuse potential of hydrocodone ER (intact and finely crushed) was significantly lower than hydrocodone IR in healthy, nondependent, recreational opioid users. Hydrocodone ER was generally well tolerated. PMID:27330154

  3. Study on the Formulation Optimization and Preparation Technology of Pioglitazone Hydrocloride Sustained-release Tablets%盐酸吡格列酮缓释片处方筛选及工艺研究

    Institute of Scientific and Technical Information of China (English)

    陈吉生; 陈燕忠; 庄文斌; 黎行山

    2012-01-01

    OBJECTIVE: To screen the formulation of Pioglitazone hydrocloride sustained-release tablets, and to optimize the preparation technology of it. METHODS: The type, amount and preparation technology of matrix material, bulking agent, and adhesive were investigated by determining accumulative rate of pioglitazone at different time in PBS to determine the formulation and preparation technology of tablet core. RESULTS: The tablet core was prepared with HPMC(K15M) as matrix material, microcrys-taline celulose as the bulking agent and 70% ethanol solution of 2% HPMC(E5) as adhesive material for Pioglitazone hydrocloride sustained-release tablets. The tablet was prepared by film coating method using 70% ethanol solution of Opadry as film coating material. Accumulative drug release rate of prepared 3 batches of samples were all more than 90% in 12 h. CONCLUSION: The preparation method is simple and the tablet is up to the requirements of sustained-release preparation.%目的:对盐酸吡格列酮缓释片进行处方筛选及工艺研究.方法:通过测定不同时间吡格列酮在pH6.8磷酸盐缓冲液中的累积释药率,对缓释骨架材料、填充剂、黏合剂的种类或规格、用量及工艺等进行考察,确立片芯处方及制备工艺.结果:片芯处方以羟丙基甲基纤维素(HPMC) (K15M)为骨架材料,微晶纤维素为填充剂,2%HPMC(E5)的70%乙醇溶液为黏合剂;制备工艺采用薄膜包衣法,以欧巴代的70%乙醇溶液作为薄膜包衣材料;所制3批样品12h的累积释药率均在90%以上.结论:本制剂工艺简单,符合缓释制剂要求.

  4. Delayed release of chloramphenicol from poly(2-hydroxyethylmethacrylate-co-acrylamide)hydrogels%Poly(HEMA-co-AAm)水凝胶对氯霉素的缓释作用

    Institute of Scientific and Technical Information of China (English)

    崔英德; 黎新明

    2008-01-01

    @@ Introduction The success of the therapy with ophthalmic drugs strongly depends on achieving enough drug concentration on the cornea for a sufficient period of time,but the typical delivery of drugs by eye-drops which currently account for more than 90% of all ophthalmic formulations is very inefficient and in some instances leads to serious side effects[1-3].Soft contact lenses have been proposed as a new vehicle for ophthalmic drug delivery[4].

  5. Synthesis, properties, and in vivo evaluation of sustained release albumin-mitoxantrone microsphere formulations for nonsystemic treatment of breast cancer and other high mortality cancers

    Science.gov (United States)

    Hadba, Ahmad Robert

    Methods for preparing mitoxantrone (MXN)-loaded albumin microspheres for the treatment of breast cancer were developed. The effect of processing conditions on the particle size of unloaded and MXN-loaded microspheres was evaluated using multivariate analyses. The data suggested that the particle size of unloaded microspheres increased as protein concentration increased or the steric stabilizer concentration decreased. In addition, synergy between these two variables was observed. In situ-loading of MXN achieved loading efficiencies in excess of 80%. Comparable efficiencies were achieved with postsynthesis loading when the microsphere were prepared from albumin-poly(glutamic acid) blends. In vitro release of MXN in phosphate buffered saline under infinite sink conditions showed that the total amount of drug released increased as the glutaraldehyde concentration decreased. This trend was reversed when the microspheres were incubated in plasma. Nanoparticles were also prepared using ethanol desolvation. These particles were dispersible in saline and easily modified with amino acids. In addition, particle size could be varied by use of different non-ionic surfactants in the preparation. The effect of intratumoral (IT) versus intravenous (IV) drug administration on tumor response and systemic toxicity was investigated in vivo using the 16/C murine mammary adenocarcinoma tumor model. The data suggested that IT-treated animals had significantly smaller tumors and lower weight loss when compared to IV-treated animals. Furthermore, the addition of surgery to the chemotherapy further improved the survival of the animals. Pilot studies using MXN-albumin microspheres suggested that microspheres could be safely administered IT in doses up to 48 mg/kg. However, there was no evidence that this higher dose resulted in improved long term survival when compared to the 32 mg/kg dose. The maximum tolerated dose of MAN given IT was approximately 12 mg/kg. The animal studies suggested

  6. Bioavailability of immediate and controlled release formulations of lithium carbonate Biodisponibilidade de formulações de liberação imediata e controlada de carbonato de lítio

    Directory of Open Access Journals (Sweden)

    Luciana Vismari

    2002-06-01

    Full Text Available INTRODUCTION/OBJECTIVES: Controlled-release lithium formulations were developed to minimize elevated blood peaks, related to side-effects and intoxications. However, there is little information about the bioavailability of the only controlled-release lithium formulation available in Brazil. The objective of this study was to compare the bioavailability of controlled-release and immediate-release lithium formulations, after single and multiple doses. METHODS: Twelve healthy volunteers received 900 mg of immediate-release or controlled-release lithium carbonate in single or multiple doses during 9 days. After single dose administration, the following parameters were analyzed for each formulation: maximum lithium concentration (Cmax; time to reach Cmax (t max; area under the curve of serum concentration versus time (AUC0-12 and AUC0-¥ and the elimination half-life (t1/2 elim.. After multiple doses, Cmax; t max; AUC0-12; mean (Cmean and minimum drug concentration (Cmin and degree of fluctuation (DF were analyzed. A 90% confidence interval (90%CI for the ratio between the AUCs for each formulation was constructed. RESULTS/DISCUSSION: Following single dose, the two formulations were bioequivalent; however, they were not after multiple doses. This fact could be a consequence of methodological limitations of lithium level's measurements since, following single dose, these levels could not be detected at time periods 24 and 48h in many volunteers, compromising the calculation of t1/2 elim ,and consequently of the AUC0-¥ and the 90%CI to the ratio of these areas. Therefore, the bioequivalence found after single dose may be an unreliable result.INTRODUÇÃO/OBJETIVO: Formulações de liberação controlada de lítio foram produzidas para minimizar picos sangüíneos elevados relacionados a efeitos colaterais e intoxicações. No entanto, o único produto com liberação controlada de lítio disponível no Brasil possui poucas informações a respeito de

  7. Fast dispersible/slow releasing ibuprofen tablets.

    Science.gov (United States)

    Fini, Adamo; Bergamante, Valentina; Ceschel, Gian Carlo; Ronchi, Celestino; de Moraes, Carlos Alberto Fonseca

    2008-05-01

    Eight formulations were developed containing ibuprofen in the form of orally disintegrating tablets. To prevent bitter taste and side effects of the drug, the drug was associated with Phospholipon 80H, a saturated lecithin, by wet granulation. The granules were then coated using different film forming agents (Kollicoat SR 30, Amprac 01, Kollidon 90F, Eudragit RD 100) obtaining four lots 1-4. Coated granules were then formulated with a sweetener (Aspartame), a mannitol-based diluent (Pearlitol SD 200) and Kollidon CL (1-4K) or Explotab (1-4E) were added as superdisintegrants and compacted under low compression force. The eight lots of tablets, 1-4K and 1-4E, were assessed if suitable as oral disintegrating tablets by determination of a range of technological parameters. Wetting and disintegregation time matched with the requirements of EP IV Ed., for almost all these formulations. Dissolution profiles suggested that the combined action of the hydrophobic lecithin and the coating delay the release of the drug from tablets with respect to when it is free or in the form of simple granules. By an appropriate combination of excipients it was thus possible to obtain orally disintegrating tablets and a delayed release of ibuprofen using simple and conventional techniques.

  8. An innovative method for the preparation of high API-loaded hollow spherical granules for use in controlled-release formulation.

    Science.gov (United States)

    Asada, Takumi; Kobiki, Mitsuaki; Ochiai, Yasushi; Iwao, Yasunori; Itai, Shigeru

    2017-05-15

    The aim of this study was to prepare controlled-release (CR) granules with suitable particle strength, flowability, particle size distribution (PSD) and density characteristics for blending with other excipients. We also wanted these CR granules to contain large quantities of active pharmaceutical ingredient (API). A high shear mixer was used to mix an API with various polymers at various feed ratios, and the resulting granulated materials were sprayed with solvent. The wet granules were dried using a fluidized bed dryer to give CR granules. The API content of the granules was determined to be 95wt%. The granules were found to be spherical in shape with smooth surfaces by scanning electron microscopy. The inner structure of each granule was determined to be hollow by X-ray computed tomography, highlighting the unusual mechanism of this granulation process. The PSD of the granules was found to be dependent on that of the constituent polymer, and a narrow PSD was obtained by adjusting the PSD of the polymer. The dissolution profile of the granules was also dependent on the constituent polymer. Taken together, these results show that we have successfully developed a new manufacturing technology for the simple and low-cost preparation of ideal CR granules. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Dissolution of tablet-in-tablet formulations studied with ATR-FTIR spectroscopic imaging.

    Science.gov (United States)

    Wray, Patrick S; Clarke, Graham S; Kazarian, Sergei G

    2013-03-12

    This work uses ATR-FTIR spectroscopic imaging to study the dissolution of delayed release and pH resistant compressed coating pharmaceutical tablets. Tablets with an inner core and outer shell were constructed using a custom designed compaction cell. The core of the delayed release tablets consisted of hydroxypropyl methylcellulose (HPMC) and caffeine. The shell consisted of microcrystalline cellulose (MCC) and glucose. The core of the pH resistant formulations was an ibuprofen and PEG melt and the shell was constructed from HPMC and a basic buffer. UV/vis spectroscopy was used to monitor the lag-time of drug release and visible optical video imaging was used as a complementary imaging technique with a larger field of view. Two delayed release mechanisms were established. For tablets with soluble shell sections, lag-time was dependent upon rapid shell dissolution. For tablets with less soluble shells, the lag-time was controlled by the rate of dissolution medium ingress through the shell and the subsequent expansion of the wet HPMC core. The pH resistant formulations prevented crystallization of the ibuprofen in the core during dissolution despite an acidic dissolution medium. FTIR imaging produced important information about the physical and chemical processes occurring at the interface between tablet sections during dissolution.

  10. Niosomal Formulation Of Orlistat: Formulation And In-Vitro Evaluation

    Directory of Open Access Journals (Sweden)

    SAMYUKTHA RANI. B

    2011-06-01

    Full Text Available The purpose of the research was to prepare Orlistat niosomes from proniosome to improve its poor and variable oral bioavailability. The non-ionic surfactant vesicles are prepared by the reverse phase evaporation technique (slurry method. The slurry of - Cyclodextrin and Span 60 was dried to form a free flowing powder in rotary flash evaporator which could be rehydrated by addition of buffer (0.5% NaCl with 3% SLS at pH 6.0. The lipid mixture consisted of cholesterol, Span 60 and - Cyclodextrin carrier in molar ratios of (0.1:0.9:1 to 0.9:0.1:1 respectively. The niosomal formulations were evaluated for particle size, entrapment efficiency, in-vitro drug release, release kinetics, Interactions and compatibility (FT-IR, surface morphology (SEM, stability studies, conductivity and sedimentation rate, pH density, viscosity. The formulation OT9 which showed higher entrapment efficiency of 44.09% and invitro releases of 94.59% at the end of 12hrs was found to be best among all the 9 formulations. Release was best fitted with Hixson kinetics and it shows that the drug release may follow diffusion mechanism. FT-IR data revealed that, compatible and there were no interactions between the drug and excipients added in the formulation. SEM images of niosomes with various magnifications revealed the mean size of the niosomes were 100 nm with smooth surface. Niosome formulation has showed appropriate stability for 90 days by storing the formulation at room temperature. Thus the niosomal formulations could be a promising delivery system for Orlistat with improved oral bioavailability, stability and for sustained drug release.

  11. A comparison of oral controlled-release morphine and oxycodone with transdermal formulations of buprenorphine and fentanyl in the treatment of severe pain in cancer patients

    Directory of Open Access Journals (Sweden)

    Nosek K

    2017-08-01

    Full Text Available Krzysztof Nosek,1 Wojciech Leppert,2,3 Hanna Nosek,4 Jerzy Wordliczek,5 Dariusz Onichimowski6 1Non–public Saint Lazarius Health Care Unit, Biskupiec, 2Chair and Department of Palliative Medicine, Poznan University of Medical Sciences, Poznań, 3Department of Quality of life Research, Gdańsk Medical University, Gdańsk, 4Department of Paediatrics, Regional Children Specialized Hospital, Olsztyn, 5Department of Interdisciplinary Intensive Care, Jagiellonian University College of Medicine, Kraków, 6Department of Intensive Care, Regional Hospital, Olsztyn, Poland Aim of the study: To compare analgesia and adverse effects during oral morphine and oxycodone and transdermal fentanyl and buprenorphine administration in cancer patients with pain. Patients and methods: Cancer patients treated at home and in outpatient clinics with severe pain (numerical rating scale score 6–10 fail to respond to non-opioids and/or weak opioids. All patients were randomized to either morphine, oxycodone, fentanyl or buprenorphine and divided into subgroups with predominant neuropathic and nociceptive pain component. Doses of opioids were titrated to satisfactory analgesia and acceptable adverse effects intensity. Patients were assessed at baseline and followed for 28 days. In all patient groups, immediate-release oral morphine was the rescue analgesic and lactulose 10 mL twice daily was the prophylaxis of constipation; no antiemetics were used as prophylaxis. Results: A total of 62 patients participated and 53 patients completed the study. Good analgesia was obtained for all 4 opioids, for both nociceptive and neuropathic pain. The use of co-analgesics was greater in patients with neuropathic pain. Morphine treatment was associated with less negative impact of pain on ability to walk, work and activity (trend according to Brief Pain Inventory-Short Form scores and less consumption of rescue morphine. The most common adverse effects included nausea and drowsiness

  12. Review of immediate-release omeprazole for the treatment of gastric acid-related disorders.

    Science.gov (United States)

    Castell, Donald

    2005-11-01

    Immediate-release omeprazole (Zegerid, Santarus) is the first immediate-release oral proton pump inhibitor to reach the market. As a powder formulation for oral suspension, it is indicated for the treatment of gastroesophageal reflux disease, erosive oesophagitis, duodenal ulcer and gastric ulcer, and is the only proton pump inhibitor approved for the reduction of risk of upper gastrointestinal bleeding in critically ill patients. Administration of immediate-release omeprazole at bedtime results in a rapid and sustained elevation of gastric pH, and seems to provide better night time control of gastric acidity than that observed with conventional morning dosing of delayed-release proton pump inhibitors. The immediate-release formulation may provide a good treatment option for patients who require flexible dosing, quick onset of action and nocturnal gastric acid control.

  13. 啶虫脒--木质素季铵盐--膨润土缓释剂的制备及性能%Preparation and performance of acetaniprid-lignin quaternary ammonium salt-bentonite slow release formulation

    Institute of Scientific and Technical Information of China (English)

    田金玲; 任世学; 方桂珍

    2015-01-01

    为了提高木质素产品的附加值,以木质素季铵盐为改性剂、钠基膨润土为原料,制备了不同季铵盐载量的膨润土。通过FTIR表征改性膨润土结构,并采用XRD分析其底面间距。以啶虫脒为药物释放的对象、改性膨润土作为释放的主要载体,利用浸渍吸附的方法制备出了啶虫脒缓释剂,并研究其缓释性能。结果表明:啶虫脒在改性膨润土上的吸附量随着木质素季铵盐载量的增加而先增大后减少。当木质素季铵盐载量相当于膨润土阳离子交换容量(CEC)的0.8倍时制备的改性膨润土(L-0.8Bt)对啶虫脒的吸附效果最佳,最大吸附量为315 mg/g。制备啶虫脒缓释剂的最佳工艺条件为L-0.8Bt用量0.02 g、吸附时间4 h、啶虫脒质量浓度500 mg/L、pH值6。药水比例和温度对载药L-0.8Bt的缓释快慢有一定影响。%In order to increase the added value of lignin products, bentonites with different loading dosages of lignin quaternary ammonium salt ( LQAS ) were synthesized with sodium-based bentonite as the raw material and LQAS as the modification agent. The morphological structure of bentonite was modified by FTIR, and the basal spacing of modified bentonite was analyzed with XRD. Acetaniprid was selected as the research object for release, and the modified bentonite as main carrier for the release. Acetaniprid slow-release formulation was prepared by means of leaching and adsorption, and its performance was studied. The results showed that with the increase of LQAS dosage, the adsorption capacity of acetaniprid in modified bentonite first increased and then decreased. The adsorption effect of modified bentonite ( L-0. 8Bt) was optimum with the maximum adsorption capacity of 315 mg/g when L-0. 8Bt prepared with dosage of LQAS was 0. 8 times cation exchange capacity ( CEC) in bentonite. The optimal preparation conditions for the acetaniprid slow-release formulation were:L-0. 8Bt dosage 0. 02 g

  14. Delayed Puberty

    DEFF Research Database (Denmark)

    Kolby, Nanna; Busch, Alexander Siegfried; Juul, Anders

    2017-01-01

    Delayed puberty can be a source of great concern and anxiety, although it usually is caused by a self-limiting variant of the normal physiological timing named constitutional delay of growth and puberty (CDGP). Delayed puberty can, however, also be the first presentation of a permanent condition ...... mineral density) and psychological (e.g., low self-esteem) and underline the importance of careful clinical assessment of the patients.......Delayed puberty can be a source of great concern and anxiety, although it usually is caused by a self-limiting variant of the normal physiological timing named constitutional delay of growth and puberty (CDGP). Delayed puberty can, however, also be the first presentation of a permanent condition...

  15. Delayed fission

    Energy Technology Data Exchange (ETDEWEB)

    Hatsukawa, Yuichi [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment

    1997-07-01

    Delayed fission is a nuclear decay process that couples {beta} decay and fission. In the delayed fission process, a parent nucleus undergoes {beta} decay and thereby populates excited states in the daughter. If these states are of energies comparable to or greater than the fission barrier of the daughter, then fission may compete with other decay modes of the excited states in the daughter. In this paper, mechanism and some experiments of the delayed fission will be discussed. (author)

  16. Erosion characteristics of an erodible tablet incorporated in a time-delayed capsule device.

    Science.gov (United States)

    McConville, Jason T; Ross, Alistair C; Florence, Alastair J; Stevens, Howard N E

    2005-01-01

    A time-delayed oral drug delivery device was investigated in which an erodible tablet (ET), sealing the mouth of an insoluble capsule, controlled the lag-time prior to drug release. The time-delayed capsule (TDC) lag-time may be altered by manipulation of the excipients used in the preparation of the ET. Erosion rates and drug release profiles from TDCs were investigated with four different excipient admixtures with lactose: calcium sulphate dihydrate (CSD), dicalcium phosphate (DCP), hydroxypropylmethyl cellulose (HPMC; Methocel K100LV grade) and silicified microcrystalline cellulose (SMCC; Prosolv 90 grade). Additionally, the compressibility of different insoluble coated capsules was tested at different moisture levels to determine their overall integrity and suitability for oral delivery. Erosion rates of CSD, DCP, and SMCC displayed a nonlinear relationship to their concentration, while HPMC indicated rapid first-order erosion followed by zero-order erosion, the onset of which was dependent on the HPMC concentration. Capsule integrity was confirmed to be most suitable for oral delivery when the insoluble ethyl cellulose coat was applied to a hard gelatin capsule using an organic spray coating process. T50% drug release times varied between 245 (+/-33.4) and 393 (+/-40.8) minutes for 8% and 20% DCP, respectively, T50% release times of 91 (+/-22.1) and 167 (+/-34.6) were observed for 8% and 20% CSD; both formulations showed incidence of premature drug release. The SMCC formulations showed high variability due to lamination effects. The HPMC formulations had T50% release times of 69 (+/-13.9), 213 (+/-25.4), and 325 (+/-30.3) minutes for 15%, 24%, and 30% HPMC concentrations respectively, with no premature drug release. In conclusion, HPMC showed the highest reproducibility for a range of time-delayed drug release from the assembled capsule formulation. The method of capsule coating was confirmed to be important by investigation of the overall capsule integrity at

  17. Efficacy and tolerability of a hydrocodone extended-release tablet formulated with abuse-deterrence technology for the treatment of moderate-to-severe chronic pain in patients with osteoarthritis or low back pain

    Directory of Open Access Journals (Sweden)

    Hale ME

    2015-09-01

    Full Text Available Martin E Hale,1 Charles Laudadio,2 Ronghua Yang,2 Arvind Narayana,2 Richard Malamut2 1Gold Coast Research, LLC, Plantation, FL, 2Teva Branded Pharmaceutical Products R & D, Inc., Frazer, PA, USA Abstract: This double-blind, placebo-controlled study evaluated the efficacy and safety of hydrocodone extended release (ER developed with abuse-deterrence technology to provide sustained pain relief and limit effects of alcohol and tablet manipulation on drug release. Eligible patients with chronic moderate-to-severe low back or osteoarthritis pain were titrated to an analgesic dose of hydrocodone ER (15–90 mg and randomized to placebo or hydrocodone ER every 12 hours. The primary efficacy measure was change from baseline to week 12 in weekly average pain intensity (API; 0=no pain, 10=worst pain imaginable. Secondary measures included percentage of patients with >33% and >50% increases from baseline in weekly API, change from baseline in weekly worst pain intensity, supplemental opioid usage, aberrant drug-use behaviors, and adverse events. Overall, 294 patients were randomized and received ≥1 dose of placebo (n=148 or hydrocodone ER (n=146. Weekly API did not differ significantly between hydrocodone ER and placebo at week 12 (P=0.134; although, in post hoc analyses, the change in weekly API was significantly lower with hydrocodone ER when excluding the lowest dose (15 mg; least squares mean, –0.20 vs 0.40; P=0.032. Significantly more patients had .33% and .50% increase in weekly API with placebo (P<0.05, and mean weekly worst pain intensity was significantly lower with hydrocodone ER at week 12 (P=0.026. Supplemental medication usage was higher with placebo (86% than hydrocodone ER (79%. Incidence of aberrant drug-use behaviors was low, and adverse events were similar between groups. This study did not meet the primary endpoint, although results support the effectiveness of this hydrocodone ER formulation in managing chronic low back or

  18. Evaluation of Quality of Life, Functioning, Disability, and Work/School Productivity Following Treatment with an Extended-Release Hydrocodone Tablet Formulated with Abuse-Deterrence Technology: A 12-month Open-label Study in Patients with Chronic Pain.

    Science.gov (United States)

    Hale, Martin E; Zimmerman, Thomas R; Ma, Yuju; Malamut, Richard

    2017-02-01

    This phase 3 study evaluated quality of life, functioning, and productivity after treatment with extended-release (ER) hydrocodone formulated with CIMA(®) Abuse-Deterrence Technology platform. Patients with chronic pain were rolled over from a 12-week placebo-controlled hydrocodone ER study or were newly enrolled. Hydrocodone ER doses were titrated (15 to 90 mg every 12 hours) to an analgesic dose, and patients received up to 52 weeks of open-label treatment. Assessments included Clinician Assessment of Patient Function (CAPF), Patient Assessment of Function (PAF), Brief Pain Inventory-Short Form (BPI-SF), 36-item Short-Form Health Survey (SF-36), Sheehan Disability Scale (SDS), and World Health Organization Health and Work Performance Questionnaire-Short Form (HPQ-SF). Of 330 enrolled patients, 291 composed the full analysis population. By week 4, ≥ 50% of patients showed improvement from baseline in all 5 CAPF domains (general activities, walking, work/daily living, relationships, and enjoyment of life) and 6 of 7 PAF domains (work attendance, work performance, walking, exercise, socializing, and enjoying life). Mean decreases from baseline of 2 to 3 points were noted for BPI-SF pain interference questions from week 4 through endpoint. Mean improvements from baseline to endpoint in SF-36 subscales ranged from 3.3 to 22.3, and SDS scores improved from moderate (4.8 to 5.1) to mild (2.5 to 2.8) disruptions in work/school, social life, and family life. At endpoint, mean HPQ-SF absolute absenteeism scores decreased from 13.6 to 10.0 hours lost/month and absolute presenteeism scores improved from 67.0 to 77.1. Patients receiving hydrocodone ER showed early numeric improvements in functioning that continued throughout this 12-month study. © 2016 World Institute of Pain.

  19. Lanreotide extended-release aqueous-gel formulation, injected by patient, partner or healthcare provider in patients with acromegaly in the United States: 1-year data from the SODA registry.

    Science.gov (United States)

    Salvatori, Roberto; Woodmansee, Whitney W; Molitch, Mark; Gordon, Murray B; Lomax, Kathleen G

    2014-02-01

    Lanreotide depot (LD; commercial name Somatuline(®) Depot) is an injectable, extended-release formulation of the synthetic somatostatin analog (SSA) lanreotide. In recent clinical trials, LD was found to be suitable for self or partner administration, avoiding the need to travel to a medical facility. The Somatuline(®) Depot for Acromegaly (SODA) study is an ongoing, multicenter, observational study in the US investigating the efficacy, safety, convenience and symptom relief provided by LD in patients with acromegaly. Sub-analyses explore outcomes according to who administered the injection: patient, partner, healthcare provider (HCP) or a combination. Data reported here reflect one year of patient experience. Patients are eligible for inclusion if they have a diagnosis of acromegaly, are treated with LD and can give signed informed consent. Baseline data include patient demographics, previous acromegaly treatment and investigations, GH and IGF-I levels, LD dose and dose adjustment frequency. Symptom frequency, injection pain and treatment convenience are assessed using patient-reported questionnaires. As of 18 April 2012, 166 patients had enrolled in SODA. Most (72 %) achieved normal IGF-I levels after 12 months of LD treatment. Disease control was similar in self or partner injectors and in patients who received injections from their HCP, although self or partner injecting was deemed more convenient. LD was well-tolerated irrespective of who performed the injection. Self injection led to more injection-site reactions, but this did not increase the rate of treatment interruption. Acromegaly symptoms remained stable. Biochemical, safety and convenience data support the clinical validity of injecting LD at home.

  20. Film coatings for oral pulsatile release.

    Science.gov (United States)

    Maroni, Alessandra; Zema, Lucia; Loreti, Giulia; Palugan, Luca; Gazzaniga, Andrea

    2013-12-05

    Pulsatile delivery is generally intended as a release of the active ingredient that is delayed for a programmable period of time to meet particular chronotherapeutic needs and, in the case of oral administration, also target distal intestinal regions, such as the colon. Most oral pulsatile delivery platforms consist in coated formulations wherein the applied polymer serves as the release-controlling agent. When exposed to aqueous media, the coating initially performs as a protective barrier and, subsequently, undergoes a timely failure based on diverse mechanisms depending on its physico-chemical and formulation characteristics. Indeed, it may be ruptured because of the gradual expansion of the core, swell and/or erode due to the glassy-rubbery polymer transition or become permeable thus allowing the drug molecules to diffuse outwards. Otherwise, when the coating is a semipermeable membrane provided with one or more orifices, the drug is released through the latter as a result of an osmotic water influx. The vast majority of pulsatile delivery systems described so far have been prepared by spray-coating, which offers important versatility and feasibility advantages over other techniques such as press- and dip-coating. In the present article, the design, manufacturing and performance of spray-coated pulsatile delivery platforms is thus reviewed.

  1. Delay Variation Model with Two Service Queues

    Directory of Open Access Journals (Sweden)

    Filip Rezac

    2010-01-01

    Full Text Available Delay in VoIP technology is very unpleasant issue and therefore a voice packets prioritization must be ensured. To maintain the high call quality a maximum information delivery time from the sender to the recipient is set to 150 ms. This paper focuses on the design of a mathematical model of end-to-end delay of a VoIP connection, in particular on a delay variation. It describes all partial delay components and mechanisms, their generation, facilities and mathematical formulations. A new approach to the delay variation model is presented and its validation has been done by experimention.

  2. 基于信息不对称的物流金融风险缓释探讨%Researches Based on the Information Asymmetry of Logistics Financial Risks Delay Release

    Institute of Scientific and Technical Information of China (English)

    储雪俭; 胥丽莉

    2011-01-01

    As we all know that the present key problems of logistics financial are risk problems.Taking off from enhancing the practicability of logistics financial,the thesis adopts three-dimensional stereogram to analyze and concludes nine major risks.In allusion to these risks,the paper has carried on visualization design based on Internet of things and put forward relevant risk management approaches,which will provide suggestions and opinions for information asymmetry of logistics financial risks delay release.%风险是目前物流金融的关键问题。文章以增强物流金融的实用性为出发点,采用三维立体图分析得出了信息不对称下物流金融的九大风险。针对这些风险,文章进行了基于物联网的可视化设计,并提出了相应的风险管理方法,为信息不对称下物流金融风险的缓释提供了建议与意见。

  3. The Effect of Ethanol on the Release of Opioids from Oral Prolonged-Release Preparations

    OpenAIRE

    Walden, Malcolm; Nicholls, Fiona A.; Smith, Kevin J.; Tucker, Geoffrey T

    2007-01-01

    Recent experience has prompted the US FDA to consider whether ethanol ingestion may modify the release characteristics of prolonged-release formulations, where dose dumping may be an issue for patient safety. The influence of ethanol on the in vitro release of opioid drugs from some prolonged-release formulations utilizing different release technologies was examined. Results indicated that the prolonged-release mechanisms remained intact under the testing conditions, although one product show...

  4. A STAGE-STRUCTURED SI ECO-EPIDEMIOLOGICAL MODEL WITH TIME DELAY AND IMPULSIVE CONTROLLING

    Institute of Scientific and Technical Information of China (English)

    Xinzhu MENG; Lansun CHEN

    2008-01-01

    This paper formulates a robust stage-structured SI eco-epidemiological model with periodic constant pulse releasing of infectious pests with pathogens. The authors show that the conditions for global attractivity of the 'pest-eradication' periodic solution and permanence of the system depend on time delay, hence, the authors call it "profitless". Further, the authors present a pest management strategy in which the pest population is kept under the economic threshold level (ETL) when the pest population is uniformly persistent. By numerical analysis, the authors also show that constant maturation time delay for the susceptible pests and pulse releasing of the infectious pests can bring obvious effects on the dynamics of system.

  5. The efficacy and safety of bupropion sustained-release formulation for the treatment of major depressive disorder: a multi-center, randomized, double-blind, placebo-controlled study in Asian patients

    Directory of Open Access Journals (Sweden)

    Koshino Y

    2013-08-01

    Full Text Available Yoshifumi Koshino,1 Won-Myong Bahk,2 Hideaki Sakai,3 Takayuki Kobayashi4 1Iris Medical Clinic, Kanazawa University, Ishikawa, Japan; 2Yeouido St Mary’s Hospital, The Catholic University of Korea, Seoul, South Korea; 3Meguro Station East Mental Clinic, Shinagawa, Tokyo, Japan; 4Medicines Development (Neurosciences, Development and Medical Affairs, GlaxoSmithKline, Shibuya, Tokyo, Japan Abstract: This study was conducted to compare the efficacy and safety of bupropion sustained-release (SR formulation orally administered at daily doses of 150 mg/day (once daily and 300 mg/day (150 mg twice daily for 8 weeks versus placebo in Asian patients with major depressive disorder. The mean change from baseline in Montgomery–Åsberg Depression Rating Scale (MADRS total score at week 8 was compared between each of the bupropion SR dose groups and the placebo group using an analysis of covariance with the multiplicity adjustment by Dunnett’s step-down procedure. A total of 569 subjects met all of the inclusion criteria and proceeded to the treatment phase. The subjects proceeding to the treatment phase included 454 Japanese patients and 115 Korean patients. There was no statistically significant difference between each of the bupropion SR dose groups and the placebo group in the primary efficacy endpoint of change from baseline in MADRS total score at week 8. Similar results were generally obtained for all of the secondary efficacy endpoints. The secondary analysis and the other subgroup analysis did not show a statistically significant difference in efficacy. There was no substantial difference in the type, severity, and incidence of adverse events (AEs between the bupropion SR dose groups and the placebo group, which indicates a favorable safety profile for bupropion SR. There were no significant findings in subjects treated with bupropion SR in regard to sexual dysfunction, weight change, and withdrawal syndrome, which are frequently recognized as

  6. Effects of a sustained release formulation of 1,25-dihydroxyvitamin D3-glycosides for milk fever prevention on serum 1,25-dihydroxyvitamin D3, calcium and phosphorus in dairy cows.

    Science.gov (United States)

    Bachmann, Heinrich; Lanz, Michael; Kehrle, Susanne; Bittner, Wolfgang; Toggenburger, Annick; Mathis, Georg A; Rambeck, Walter

    2017-10-01

    Milk fever (MF) is a metabolic disease in dairy cows around parturition. The clinical lead sign is muscular paresis leading in severe cases to paralysis of the affected animal. Multiparturient animals of high performing dairy breeds are most likely to be affected and have a high probability of recurrence. An acute drop in blood calcium levels causes the disease when the demand for calcium at the onset of lactation exceeds the ability to replete blood calcium levels through mobilization from bone and intestinal uptake. With the understanding of the underlying mechanism, calcium supply management and vitamin D supplementation became prime candidates for MF prevention and therapy. Several strategies have been developed for MF prevention. Application of the active form of Vitamin D, 1,25(OH)2D3, was found to prevent MF effectively. In order to prevent a delayed hypocalcemia, which was occasionally seen after stopping the treatment with 1,25(OH)2D3, a new approach was chosen by applying Solanum glaucophyllum extract (SGE), which contains 1,25(OH)2D3-glycosides, as instant-release (irSGE) in combination with slow-release (srSGE) tablets. In a first study, non-lactating cows were treated with a single bolus of either synthetic 1,25(OH)2D3, irSGE, or srSGE and the results were compared to a control group without treatment. Blood serum levels of 1,25(OH)2D3 (1,25D), calcium (Ca), phosphate (P) and magnesium (Mg) were followed for 11days and the area under the curve (AUC) was calculated. Calcium and phosphate excretion in urine were determined during 15days. While serum concentration of 1,25(OH)2D3 was back to pre-treatment level in the irSGE, srSGE and 1,25(OH)2D3 treated group within 3days, calcium and phosphate levels remained elevated for up to 9days. AUC of serum 1,25(OH)2D3 was 2.89 (1,25D), 3.13 (irSGE) and 4.21 (srSGE) times higher than control. Serum calcium levels were 1.07(*) (for 1.25D); 1.08(*) (for irSGE) and 1.12(*) (for srSGE) times higher than control. Serum

  7. Suppressed Release of Clarithromycin from Tablets by Crystalline Phase Transition of Metastable Polymorph Form I.

    Science.gov (United States)

    Fujiki, Sadahiro; Watanabe, Narumi; Iwao, Yasunori; Noguchi, Shuji; Mizoguchi, Midori; Iwamura, Takeru; Itai, Shigeru

    2015-08-01

    The pharmaceutical properties of clarithromycin (CAM) tablets containing the metastable form I of crystalline CAM were investigated. Although the dissolution rate of form I was higher than that of stable form II, the release of CAM from form I tablet was delayed. Disintegration test and liquid penetration test showed that the disintegration of the tablet delayed because of the slow penetration of an external solution into form I tablet. Investigation by scanning electron microscopy revealed that the surface of form I tablet was covered with fine needle-shaped crystals following an exposure to the external solution. These crystals were identified as form IV crystals by powder X-ray diffraction. The phenomenon that CAM releases from tablet was inhibited by fine crystals spontaneously formed on the tablet surface could be applied to the design of sustained-release formulation systems with high CAM contents by minimizing the amount of functional excipients. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

  8. Gastroretentive Pulsatile Release Tablets of Lercanidipine HCl: Development, Statistical Optimization, and In Vitro and In Vivo Evaluation

    Directory of Open Access Journals (Sweden)

    Gagganapalli Santhoshi Reddy

    2014-01-01

    Full Text Available The present study was aimed at the development of gastroretentive floating pulsatile release tablets (FPRTs of lercanidipine HCl to enhance the bioavailability and treat early morning surge in blood pressure. Immediate release core tablets containing lercanidipine HCl were prepared and optimized core tablets were compression-coated using buoyant layer containing polyethylene oxide (PEO WSR coagulant, sodium bicarbonate, and directly compressible lactose. FPRTs were evaluated for various in vitro physicochemical parameters, drug-excipient compatibility, buoyancy, swelling, and release studies. The optimized FPRTs were tested in vivo in New Zealand white rabbits for buoyancy and pharmacokinetics. DoE optimization of data revealed FPRTs containing PEO (20% w/w with coat weight 480 mg were promising systems exhibiting good floating behavior and lag time in drug release. Abdominal X-ray imaging of rabbits after oral administration of the tablets, confirmed the floating behavior and lag time. A quadratic model was suggested for release at 7th and 12th h and a linear model was suggested for release lag time. The FPRT formulation improved pharmacokinetic parameters compared to immediate release tablet formulation in terms of extent of absorption in rabbits. As the formulation showed delay in drug release both in vitro and in vivo, nighttime administration could be beneficial to reduce the cardiovascular complications due to early morning surge in blood pressure.

  9. Clinic Research of Calcium Sulphate Mixed with Vancomycin Delayed Released Antibiotics in the Human Body%载万古霉素硫酸钙在人体内缓释药物的临床研究#

    Institute of Scientific and Technical Information of China (English)

    张展; 张春; 张晓文; 郭峭峰; 沈立锋

    2015-01-01

    目的:探讨载万古霉素人工骨在人体内局部缓释抗生素的规律。方法:将医用硫酸钙人工骨与万古霉素混合植入创伤性骨髓炎患者体内,测量病灶内局部的抗生素浓度、每日释药量、释药百分率,同时记录上述指标何时达到高峰,以及持续维持有效浓度时间。测量患者血液中万古霉素的浓度,以及肝功能检查,进行安全性评估。并对病灶植骨处术后X检查,观察将硫酸钙人工骨显影吸收消失过程。结果:载万古霉素人工骨在人体内局部缓释出的万古霉素浓度大大超过最低抑菌浓度;而血药浓度低,肝肾功能正常;硫酸钙人工骨影在各组织中吸收时间各不相同。结论:载万古霉素硫酸钙人工骨病灶局部可以释放高浓度万古霉素,而全身浓度低,安全性高,又有骨引导作用。其在人体内的药物缓释规律,完全符合治疗骨髓炎的要求。%Objective: To discuss the law of calcium sulphate mixed with vancomycin delayed released antibiotics in the human body. Methods:We implant calcium sulphate mixed with vancomycin in the osteomyelitic human body , then measure antibiotic concentration in focus,the amount of antibiotics in focus,the percentage of antibiotics released in focus, and when these index achieve peak, how long effective antibiotic concentration can persist. The concentration of vancomycin in patient’s blood and liver function, renal function are measured to evaluate the security of osteoset mixed with vancomycin. Osteoset implanted in focus is examined with X-ray, to observe how osteoset absorbs in focus.Results:Vancomycin concentration in focus exceeds MIC, blood concentration is low; liver and renal function of patients are normal. The absorption time of calcium sulphate is different in different organization. Conclusion:Osteoset mixed with vancomycin could release high concentration of vancomycin in focus, and low concentration of

  10. Design and In Vivo Anti-Inflammatory Effect of Ketoprofen Delayed Delivery Systems.

    Science.gov (United States)

    Cerciello, Andrea; Auriemma, Giulia; Morello, Silvana; Pinto, Aldo; Del Gaudio, Pasquale; Russo, Paola; Aquino, Rita P

    2015-10-01

    For the treatment of inflammatory-based diseases affected by circadian rhythms, the development of once-daily dosage forms is required to target early morning symptoms. In this study, Zn-alginate beads containing ketoprofen (K) were developed by a tandem technique prilling/ionotropic gelation. The effect of main critical variables on particles micromeritics, inner structure as well as on drug loading and in vitro drug release was studied. The in vivo anti-inflammatory efficacy was evaluated using a modified protocol of carrageenan-induced edema in rat paw administering beads to rats by oral gavage at 0, 3, or 5 h before edema induction. Good drug loading and desired particle size and morphology were obtained for the optimized formulation F20. In vitro dissolution studies showed that F20 had a gastroresistant behavior and delayed release of the drug in simulated intestinal fluid. The in vitro delayed release pattern was clearly reflected in the prolonged anti-inflammatory effect in vivo of F20, compared to pure ketoprofen; F20, administered 3 h before edema induction, showed a significant anti-inflammatory activity, reducing maximum paw volume in response to carrageenan injection, whereas no response was observed for ketoprofen. The designed beads appear a promising platform suitable for a delayed release of anti-inflammatory drugs. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:3451-3458, 2015.

  11. Ketoprofen-loaded pomegranate seed oil nanoemulsion stabilized by pullulan: Selective antiglioma formulation for intravenous administration.

    Science.gov (United States)

    Ferreira, Luana M; Cervi, Verônica F; Gehrcke, Mailine; da Silveira, Elita F; Azambuja, Juliana H; Braganhol, Elizandra; Sari, Marcel H M; Zborowski, Vanessa A; Nogueira, Cristina W; Cruz, Letícia

    2015-06-01

    This study aimed to prepare pomegranate seed oil nanoemulsions containing ketoprofen using pullulan as a polymeric stabilizer, and to evaluate antitumor activity against in vitro glioma cells. Formulations were prepared by the spontaneous emulsification method and different concentrations of pullulan were tested. Nanoemulsions presented adequate droplet size, polydispersity index, zeta potential, pH, ketoprofen content and encapsulation efficiency. Nanoemulsions were able to delay the photodegradation profile of ketoprofen under UVC radiation, regardless of the concentration of pullulan. In vitro release study indicates that nanoemulsions were able to release approximately 95.0% of ketoprofen in 5h. Free ketoprofen and formulations were considered hemocompatible at 1 μg/mL, in a hemolysis study, for intravenous administration. In addition, a formulation containing the highest concentration of pullulan was tested against C6 cell line and demonstrated significant activity, and did not reduce fibroblasts viability. Thus, pullulan can be considered an interesting excipient to prepare nanostructured systems and nanoemulsion formulations can be considered promising alternatives for the treatment of glioma.

  12. Fabrication of controlled-release budesonide tablets via desktop (FDM) 3D printing.

    Science.gov (United States)

    Goyanes, Alvaro; Chang, Hanah; Sedough, Daniel; Hatton, Grace B; Wang, Jie; Buanz, Asma; Gaisford, Simon; Basit, Abdul W

    2015-12-30

    The aim of this work was to explore the feasibility of using fused deposition modelling (FDM) 3D printing (3DP) technology with hot melt extrusion (HME) and fluid bed coating to fabricate modified-release budesonide dosage forms. Budesonide was sucessfully loaded into polyvinyl alcohol filaments using HME. The filaments were engineered into capsule-shaped tablets (caplets) containing 9mg budesonide using a FDM 3D printer; the caplets were then overcoated with a layer of enteric polymer. The final printed formulation was tested in a dynamic dissolution bicarbonate buffer system, and two commercial budesonide products, Cortiment® (Uceris®) and Entocort®, were also investigated for comparison. Budesonide release from the Entocort® formulation was rapid in conditions of the upper small intestine while release from the Cortiment® product was more delayed and very slow. In contrast, the new 3D printed caplet formulation started to release in the mid-small intestine but release then continued in a sustained manner throughout the distal intestine and colon. This work has demonstrated the potential of combining FDM 3DP with established pharmaceutical processes, including HME and film coating, to fabricate modified release oral dosage forms.

  13. Crystallization Formulation Lab

    Data.gov (United States)

    Federal Laboratory Consortium — The Crystallization Formulation Lab fills a critical need in the process development and optimization of current and new explosives and energetic formulations. The...

  14. Effect of ethanol on the release of morphine sulfate from Oramorph SR tablets.

    Science.gov (United States)

    Barkin, Robert L; Shirazi, Dean; Kinzler, Eric

    2009-01-01

    Recent data have shown that rapid release of active drug (i.e., dose-dumping) can occur when modified-release formulations of pain medications, and other extended-release pharmacotherapies, are exposed to ethanol in vitro. Dose-dumping of sustained-release opioids is of particular concern because of the risk for serious and potentially fatal adverse events. Sustained-release morphine sulfate tablets (Oramorph SR, 15, 30, 60, and 100 mg; Xanodyne Pharmaceuticals, Inc., Newport, KY) were incubated in vitro at simulated physiologic conditions in media containing no ethanol or ethanol in concentrations ranging from 4%-40% v/v. Morphine sulfate release was measured over the course of 1 to 24 hours using a high-performance liquid chromatography method (United States Pharmacopeia). The sustained-release morphine sulfate tablets exhibited no evidence of active drug dose-dumping. Regardless of ethanol concentration, ethanol exposure did not increase the rate of release of morphine sulfate. Release of approximately 20%-25% of the morphine sulfate dose within 1 hour was consistent among the morphine doses tested and ethanol concentrations. Release of morphine sulfate from the 60- and 100-mg tablets exposed to the higher ethanol concentrations (20% and 40% ethanol) was slightly delayed at all time points beyond 1 hour. The results of this in vitro study suggest that ethanol concentrations as high as 40% do not substantially alter the sustained-release properties of the morphine sulfate tablets.

  15. Impairment of the in vitro drug release behaviour of oral modified release preparations in the presence of alcohol.

    Science.gov (United States)

    Fadda, Hala M; Mohamed, Mohamed A M; Basit, Abdul W

    2008-08-06

    Recently, there has been concern by regulatory authorities of the risk of alcohol-induced dose dumping of oral modified release (MR) formulations. The aim of this work was to use in vitro dissolution methodology to investigate the vulnerability of MR products to alcohol under different physiological conditions of the upper gastrointestinal tract. A variety of dissolution scenarios with ethanol concentrations in the range of 5-40% v/v were explored. Mesalazine (5-aminosalicylic acid) was selected as the model drug and the release behaviour of three commercially available MR, monolithic and multi-particulate preparations with pH-dependent or independent release mechanisms was evaluated (Salofalk, Asacol and Pentasa). Each product was found to have a distinctive release profile and behaved differently in the scenarios screened. In the case of Pentasa, complete dose dumping occurred on exposure to 40% ethanol in acid for 2h. Asacol, however, displayed a contrarian trend with drug release being substantially delayed in small intestinal media after pre-exposure to acid/ethanol for the same duration. Salofalk underwent accelerated drug release in the presence of ethanol in the dissolution media, with unexpected trends observed between the different scenarios. For the three preparations explored, there appears to be a complex interplay between the various formulation variables and ethanol in the dissolution media. The unpredictable release profiles under the different conditions makes it necessary to screen several in vitro scenarios of ethanol exposure for each preparation before a decision is reached on its susceptibility to drug release impairment on consumption with ethanol.

  16. Isotretinoin Oil-Based Capsule Formulation Optimization

    Directory of Open Access Journals (Sweden)

    Pi-Ju Tsai

    2013-01-01

    Full Text Available The purpose of this study was to develop and optimize an isotretinoin oil-based capsule with specific dissolution pattern. A three-factor-constrained mixture design was used to prepare the systemic model formulations. The independent factors were the components of oil-based capsule including beeswax (X1, hydrogenated coconut oil (X2, and soybean oil (X3. The drug release percentages at 10, 30, 60, and 90 min were selected as responses. The effect of formulation factors including that on responses was inspected by using response surface methodology (RSM. Multiple-response optimization was performed to search for the appropriate formulation with specific release pattern. It was found that the interaction effect of these formulation factors (X1X2, X1X3, and X2X3 showed more potential influence than that of the main factors (X1, X2, and X3. An optimal predicted formulation with Y10 min, Y30 min, Y60 min, and Y90 min release values of 12.3%, 36.7%, 73.6%, and 92.7% at X1, X2, and X3 of 5.75, 15.37, and 78.88, respectively, was developed. The new formulation was prepared and performed by the dissolution test. The similarity factor f2 was 54.8, indicating that the dissolution pattern of the new optimized formulation showed equivalence to the predicted profile.

  17. Delayed-Release Oral Mesalamine 4.8 g/day (800 mg tablets Compared with 2.4 g/day (400 mg tablets for the Treatment of Mildly to Moderately Active Ulcerative Colitis: The ASCEND I Trial

    Directory of Open Access Journals (Sweden)

    Stephen B Hanauer

    2007-01-01

    Full Text Available BACKGROUND: Delayed-release oral mesalamine 2.4 g/day to 4.8 g/day has been shown to be effective in treating mildly to moderately active ulcerative colitis (UC, but it is unknown whether an initial dose of 4.8 g/day is more effective than 2.4 g/day in patients with mildly to moderately active UC and in the subgroup with moderate disease.

  18. Formulation and characterization of rifampicin microcapsules

    Directory of Open Access Journals (Sweden)

    Md.Sarfaraz

    2010-01-01

    Full Text Available Rifampicin biodegradable microcapsules were prepared by feasible emulsification-ionic gelation method for a novel controlled release product. Sodium alginate and Carbopol 974P were used as coating polymers in different ratios 1:1, 1:2, 1:3 and 1:4 to obtain elegant microcapsules. The formulations were characterized for encapsulation efficiency, drug loading, sieve analysis, scanning electron microscopy and in vitro release studies. The microcapsules were discrete, large, almost spherical and free flowing with encapsulation efficiency in the range of 75% to 89%, drug loading 75% to 86% and size 440 µm to 500 µm. Rifampicin release from these microcapsules was slow and extended over longer periods of time depending on the polymer coat. Drug release was diffusion controlled and followed first order kinetics. The formulation MC1 with a coating ratio of 1:1 (Sodium alginate: Carbopol 974P was found to be suitable for oral controlled release.

  19. 熔融法制备非诺贝特缓释胶囊的处方工艺研究%Formulation and preparation process investigation on fenofibrate sustain-released capsule prepared by melting method

    Institute of Scientific and Technical Information of China (English)

    傅行弟

    2016-01-01

    Objective Adopt solid dispersion technique with melting method to replace micropellets-capsule method in preparation of fenofibrate sustain-released capsule.Methods Prepare sustain-released granules with active pharmaceutical ingredient(API)and excipients by melting method,and seal above granules in capsules.Using imported drugs as reference,conduct study vitro-release of self-made sustain-released capsule under the drug-release test conditions in quality standards enacted by SFDA.Results The dis-solution rate of self-made fenofibrate sustain-released capsule is basically the same as that of imported one.Conclusion The prepa-ration of fenofibrate sustain -released capsule by solid dispersion techniques with melting method is technologically accessible,and could be widely adopted in industrial manufacture.%目的:采用熔融法固体分散体技术代替微丸技术制备非诺贝特缓释胶囊。方法将主药与辅料熔融制备缓释颗粒,装入胶囊,以进口品为对照,按国家颁布的质量标准中释放度检查条件考查其释放。结果两者体外释放基本一致。结论熔融法固体分散体技术制备非诺贝特缓释胶囊较微丸技术简单方便,适合工业生产。

  20. Delay-range-dependent chaos synchronization approach under varying time-lags and delayed nonlinear coupling.

    Science.gov (United States)

    Zaheer, Muhammad Hamad; Rehan, Muhammad; Mustafa, Ghulam; Ashraf, Muhammad

    2014-11-01

    This paper proposes a novel state feedback delay-range-dependent control approach for chaos synchronization in coupled nonlinear time-delay systems. The coupling between two systems is esteemed to be nonlinear subject to time-lags. Time-varying nature of both the intrinsic and the coupling delays is incorporated to broad scope of the present study for a better-quality synchronization controller synthesis. Lyapunov-Krasovskii (LK) functional is employed to derive delay-range-dependent conditions that can be solved by means of the conventional linear matrix inequality (LMI)-tools. The resultant control approach for chaos synchronization of the master-slave time-delay systems considers non-zero lower bound of the intrinsic as well as the coupling time-delays. Further, the delay-dependent synchronization condition has been established as a special case of the proposed LK functional treatment. Furthermore, a delay-range-dependent condition, independent of the delay-rate, has been provided to address the situation when upper bound of the delay-derivative is unknown. A robust state feedback control methodology is formulated for synchronization of the time-delay chaotic networks against the L2 norm bounded perturbations by minimizing the L2 gain from the disturbance to the synchronization error. Numerical simulation results are provided for the time-delay chaotic networks to show effectiveness of the proposed delay-range-dependent chaos synchronization methodologies. Copyright © 2014 ISA. Published by Elsevier Ltd. All rights reserved.

  1. Development of a Single Ion Pair HPLC Method for Analysis of Terbinafine, Ofloxacin, Ornidazole, Clobetasol, and Two Preservatives in a Cream Formulation: Application to In Vitro Drug Release in Topical Simulated Media-Phosphate Buffer Through Rat Skin.

    Science.gov (United States)

    Dewani, Anil P; Bakal, Ravindra L; Kokate, Pranjali G; Chandewar, Anil V; Patra, Srdhanjali

    2015-01-01

    Present work reports an HPLC method with UV detection for quantification of terbinafine, ofloxacin, ornidazole, and clobetasol in a cream formulation along with two preservatives methyl and propyl paraben. The chromatographic separation and quantification was achieved by an octyl bonded column and a gradient elution program involving an ion-pairing reagent, hexanesulfonic acid (0.2%, pH modified to 2.7 using orthophosphoric acid) and acetonitrile. The method was simple and devoid of buffer salts and therefore advantageous for system and column life. The three step gradient program was initiated with 30% (v/v) acetonitrile for the first 5 min and ramped linearly to 60% in the next 7 min. The mobile phase remained constant for the next 11 min and then concluded at 30% (v/v) of acetonitrile. Flow rate throughout was 0.8 mL/min, and all the signals were monitored at 243 nm. The method was applied for assay of a cream formulation and its in vitro permeation studies to determine the penetration profile of the four drugs and two preservatives. A marketed cream formulation was selected for the permeation study, which was carried out using a diffusion cell consisting of topical simulated media, phosphate buffer (pH=6.8) solution containing 1% sodium lauryl sulfate as a receiver medium.

  2. Application of UV Imaging in Formulation Development

    DEFF Research Database (Denmark)

    Sun, Yu; Østergaard, Jesper

    2017-01-01

    defining formulation behavior after exposure to the aqueous environments and pharmaceutical performance is critical in pharmaceutical development, manufacturing and quality control of drugs. UV imaging has been explored as a tool for qualitative and quantitative characterization of drug dissolution...... and release with the characteristic feature of providing real-time visualization of the solution phase drug transport in the vicinity of the formulation. Events occurring during drug dissolution and release, such as polymer swelling, drug precipitation/recrystallization, or solvent-mediated phase transitions...

  3. Subscale testing of prompt agent defeat formulations

    Science.gov (United States)

    Knott, A.; Stamatis, D.; Svingala, F.; Lightstone, J.; Miller, K.; Bensman, M.; Bohmke, M.

    2017-01-01

    There is a need to improve the current bioagent defeat systems with formulations that produce lower peak pressure and impulse, sustained high temperatures, and release of biocidal species for prompt defeat applications. In this work, explosive charge configurations similar to fuel-air explosives were detonated in a semi-enclosed chamber configuration. Binder type and fuel-to-oxidizer ratios were varied to observe the effects on combustion performance. Thermocouple measurements and high-speed video were used to monitor the combustion of the dispersed formulation. The down-selected formulations were then tested in a sub-scale vented agent defeat system developed to evaluate performance of formulations against aerosolized Bacillus thuringiensis (Bt) spores. Diagnostics including thermocouples and piezoelectric pressure gauges were utilized to characterize the detonation event. Biological sampling with surface coupons, liquid impingement, and filters of the post detonation environment were utilized to determine spore survivability and to rank the relative effectiveness of each formulation.

  4. IT Supporting Strategy Formulation

    NARCIS (Netherlands)

    Achterbergh, J.M.I.M.

    2005-01-01

    This overview approaches information and communication technology (ICT) for competitive intelligence from the perspective of strategy formulation. It provides an ICT architecture for supporting the knowledge processes producing relevant knowledge for strategy formulation. To determine what this arch

  5. IT Supporting Strategy Formulation

    NARCIS (Netherlands)

    Achterbergh, J.M.I.M.

    2005-01-01

    This overview approaches information and communication technology (ICT) for competitive intelligence from the perspective of strategy formulation. It provides an ICT architecture for supporting the knowledge processes producing relevant knowledge for strategy formulation. To determine what this arch

  6. Torsion formulation of gravity

    Energy Technology Data Exchange (ETDEWEB)

    Lledo, M A; Sommovigo, L, E-mail: Maria.Lledo@ific.uv.e, E-mail: Luca.Sommovigo@mfn.unipmn.i [Departament de Fisica Teorica, Universitat de Valencia, and IFIC (Centro mixto CSIC-UVEG) C/Dr Moliner, 50, E-46100 Burjassot (Valencia) (Spain)

    2010-03-21

    We explain precisely what it means to have a connection with torsion as a solution of the Einstein equations. While locally the theory remains the same, the new formulation allows for topologies that would have been excluded in the standard formulation of gravity. In this formulation it is possible to couple arbitrary torsion to gauge fields without breaking the gauge invariance.

  7. Delay estimation on a railway-line with smart use of micro-simulation

    DEFF Research Database (Denmark)

    Cerreto, Fabrizio; Harrod, Steven; Nielsen, Otto Anker

    2017-01-01

    This paper formulates a delay propagation model that estimates total railway line delay as a polynomial function of a single primary delay. The estimate is derived from a finite series of delays over a horizon that spans two dimensions: the length of the railway line and the number of trains in t...

  8. Time-Delay Estimation using the Characteristic Roots of Delay Differential Equations

    Directory of Open Access Journals (Sweden)

    Sun Yi

    2012-01-01

    Full Text Available Problem statement: For ordinary dynamic systems (i.e., non-delayed, various methods such as linear least-squares, gradient-weighted least-squares, Kalman filtering and other robust techniques have been widely used in signal processing, robotics, civil engineering. On the other hand, time-delay estimation of systems with unknown time-delay is still a challenging problem due to difficulty in formulation caused. Approach: The presented method makes use of the Lambert W function and analytical solutions of scalar first-order Delay Differential Equations (DDEs. The Lambert W function has been known to be useful in solving delay differential equations. From the solutions in terms of the Lambert W function, the dominant characteristic roots can be obtained and used to estimate time-delays. The function is already embedded in various software packages (e.g., MATLAB and thus, the presented method can be readily used for time-delay systems. Results: The presented method and the provided examples show ease of formulation and accuracy of time-delay estimation. Conclusion: Estimation of time-delays can be conducted in an analytical way. The presented method will be extended to general systems of DDEs and application to physical systems.

  9. In vitro and in vivo evaluation of an oral multiple-unit formulation for colonic delivery of insulin.

    Science.gov (United States)

    Maroni, Alessandra; Del Curto, Maria Dorly; Salmaso, Stefano; Zema, Lucia; Melocchi, Alice; Caliceti, Paolo; Gazzaniga, Andrea

    2016-11-01

    A multiple-unit formulation for time-dependent colonic release of insulin was obtained by coating insulin and sodium glycocholate immediate-release minitablets with: (i) Methocel® E50, a low-viscosity hydroxypropyl methylcellulose (inner coating), (ii) 5:1 w/w Eudragit® NE/Explotab® V17, a mixture of a neutral polymethacrylate with a pore-forming superdisintegrant (intermediate coating), and (iii) Aqoat® AS, enteric-soluble hydroxypropyl methylcellulose acetate succinate (outer coating). Sodium glycocholate was added as a permeation enhancer while the inner, intermediate and outer coatings were aimed, respectively, at delaying the onset of release through swelling/erosion processes, extending the duration of the lag phase by slowing down water penetration into the underlying functional layer, and overcoming variable gastric residence time. In vitro studies showed that neither insulin nor sodium glycocholate were released from the three-layer system during 2h of testing in 0.1N HCl, while complete release of the protein and of the enhancer occurred in phosphate buffer, pH 6.8, after consistent lag phases. No significant changes were noticed in the release profiles following twelve-month storage at 4°C. Oral administration of the novel formulation to diabetic rats elicited a peak in the plasma insulin concentration after 6h, which was associated with a sharp decrease in the glycemic levels. The relative bioavailability and pharmacological availability of such a formulation, as determined vs. the uncoated tablets, were 2.2 and 10.3, respectively. Based on these results, the three-layer system presented was considered a potentially interesting tool for oral colonic delivery of insulin and adjuvant compounds.

  10. Formulation and in vitro evaluation of theophylline-Eudragit® sustained-release tablets Desenvolvimento e avaliação in vitro de comprimidos de liberação prolongada de teofilina preparados com Eudragit®

    Directory of Open Access Journals (Sweden)

    Evelyn Ojoe

    2005-09-01

    Full Text Available Tablets containing theophylline (66.67% based on a Eudragit® RS 30D and NE 30D matrices containing 10% to 30% of either of the polymer were produced by compression method. The influence of the different proportions of methacrylic esters, the use of lactose and tribasic calcium phosphate as diluents and also the effects of the addition of magnesium stearate as a hydrophobic agent lubricant on the theophylline release, were studied. Physicochemical analyses and drug content was evaluated. In vitro drug release studies were carried out in simulated gastric fluid without pepsin (pH1.2 and simulated intestinal fluid without pancreatin (pH7.5. A relatively prolonged release of theophylline from the polymer matrices for a 7 hr-release period was detected. Magnesium stearate at 0.5% and Eudragit® NE 30D at 10% was considered a better sustained-release matrix compressed theophylline tablets comparing with Eudragit® RS 30D in the same conditions (USP. Results from physicochemical analyses were in accordance with specifications. The release patterns were analyzed from the viewpoint of square-root of time and as a first-order, zero-order kinetics, and Higuchi. Additionally, half-life of release (Td50% and dissolution rates (kd were calculated. Higuchi was the model that better fitted theophylline kinetic, and diffusion controlled was involved.Comprimidos contendo teofilina (66.67% e polímeros de Eudragit® NE 30D e RS 30D entre 10 e 30% foram produzidos por compressão. A influência das diferentes proporções de ésteres do ácido metacrílico, uso da lactose e fosfato de cálcio tribásico como diluente, bem como os efeitos da adição de estearato de magnésio como agente lubrificante hidrofóbico na liberação da teofilina foram estudados. Análises físico-químicas e teor de fármaco foram avaliados. Estudos da liberação do fármaco in vitro foram conduzidos em fluido gástrico simulado (pH 1,2 e fluido intestinal simulado sem pancreatina (p

  11. Formulation Development and Optimization of Matrix Tablet of Tramadol Hydrochloride.

    Science.gov (United States)

    Deb, Pulak; Singha, Jubaraj; Chanda, Indranil; Chakraborty, Prithviraj

    2017-01-01

    The aim of the present investigation is to formulate and optimize oral sustained release matrix tablet of highly water soluble drug Tramadol HCl and to evaluate the effect of varying concentration of hydrophilic and hydrophobic polymer on drug release, based on a survey done on the recent patents of Tramadol HCl (US7374781, CA 2479252) and sustained release matrix tablets. The tablets were prepared by double granulation process, by melt granulation and wet granulation technique using Carnauba wax (CW) and HPMC K100 as release retardant. Pre and post compression factors were evaluated and all the parameters were found within the limit. The drug release data were subjected to different models in order to evaluate release kinetics and mechanism of drug release. The prepared formulations showed drug release in the range 100±2% in 6hrs, 7hrs, 8hrs and 9hrs and upto 12 hrs respectively. The optimized tablet having 25% CW and 20% HPMC showed sustained drug release pattern. Hydrophilic matrix of HPMC alone could not control the Tramadol release effectively for 12 h whereas when combined with CW could slow down the release of drug and can be successfully employed for formulating sustained-release matrix tablets. Similarity factor, f2 shows the test and reference profile are identical. Double granulation technique with CW and HPMC K100 proved as a better technique for sustaining the drug release from the matrix tablet. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  12. Study on acute toxicity test of an environment-friendly high-performance delayed-release deodorizer and its irritating effect on broken skin%环保型高效缓释除臭剂急性毒性和一次破损皮肤刺激试验的研究

    Institute of Scientific and Technical Information of China (English)

    余大为; 胡萍; 翟育忠; 何晓军; 马永华; 魏仲梅; 许小红

    2011-01-01

    目的:了解环保型高效缓释除臭剂的急性毒性强度和对破损皮肤刺激或腐蚀作用.方法:NY1109.6.3.1、6.3.2-2006.结果:小鼠的急性毒性试验采用最大耐受剂量法,一次灌胃给予5000 mg/kgBW,14 d观察期内未见明显中毒症状和死亡.家兔一次破损皮肤刺激试验均无刺激症状.结论:环保型高效缓释除臭剂属实际无毒,对皮肤无刺激性.%Objective:To investigate the acute toxicity of an environment - friendly high - performance delayed - release deodorizer and its irritating or corroding effect on broken skin.Methods: This study was carried out as per NY1109.6.3.1,6.3.2-2006 in General Technical Guidelines on Microbial Fertilizer Biosafety.Results: The maximum tolerated dose method was used for acute toxicity test of the environment - friendly high - performance delayed - release deodorizer in mice.No apparent toxic symptom or death was found in the 14d observation period following gastric administration of a single dose of 5000 mg/kg · BW.No skin irritating symptom was exhibited in the single -dose broken skin irritating test.Conclusion: The environment -friendly high- performance delayed -release deodorizer is practically non -toxic and has no skin irritating effect.

  13. Preparation of Copper-loaded Microcapsule Formulations

    Directory of Open Access Journals (Sweden)

    Nenad Jalšenjak

    2011-06-01

    Full Text Available Novel copper-loaded chitosan or chitosan/alginate based microcapsules formulations have been presented. It was shown that prolonged release of copper from microcapsules accompanied with possible prolonged presence of copper on leaves is useful in crop protection.

  14. Preparation of Copper-loaded Microcapsule Formulations

    Directory of Open Access Journals (Sweden)

    Nenad Jalšenjak

    2014-02-01

    Full Text Available Novel copper-loaded chitosan or chitosan/alginate based microcapsules formulations have been presented. It was shown that prolonged release of copper from microcapsules accompanied with possible prolonged presence of copper on leaves is useful in crop protection.

  15. Delayed childbearing.

    Science.gov (United States)

    Francis, H H

    1985-06-01

    In many Western nations, including England and Wales, Sweden, and the US, there is a current trend towards delayed childbearing because of women's pursuit of a career, later marriage, a longer interval between marriage and the 1st birth, and the increasing number of divorcees having children in a 2nd marriage. Wives of men in social classes I and II in England and Wales are, on average, having their 1st child at 27.9 years, 1.6 years later than in 1973, and in social classes IV and V, 1.0 years later than in 1973, at a mean age of 23.7 years. Consequently, the total period fertility rate for British women aged 30-34 years, 35-39 years, and 40 and over increased by 4%, 2%, and 4%, respectively, between 1982-83, in contrast to reductions of 2% and 3%, respectively, in the 15-19 year and 20-24 year age groups, with the 25-29-year-olds remaining static. The average maternal mortality for all parties in England and Wales during 1976-78 was 106/million for adolescents, 70.4/million for 20-24 year-olds, and 1162/million for those aged 40 years and older. The specific obstetric and allied conditions which increase with age are the hypertensive diseases of pregnancy, hemorrhage, pulmonary embolism, abortion, cardiac disease, caesarean section, ruptured uterus, and amniotic fluid embolism. The Swedish Medical Birth Registry of all live births and perinatal deaths since 1973 has shown that the risk of late fetal death is significantly greater in women aged 30-39 years than in those of the same parity and gravidity aged 20-24 years. The risk of giving birth to low birth weight babies preterm and at term and of premature labor are similarly increased. The early neonatal death rate also was increased for primigravidas and nulliparas in the 30-39 year age group but not in parous women. This is, in part, due to the rise in incidence of fetal abnormalities with advancing maternal age because of chromosomal and nonchromosomal anomalies. These also appear to be the cause of the

  16. Patented herbal formulations and their therapeutic applications.

    Science.gov (United States)

    Musthaba, Mohamed; Baboota, Sanjula; Athar, Tanwir M D; Thajudeen, Kamal Y; Ahmed, Sayeed; Ali, Javed

    2010-11-01

    Recently, there is a greater global interest in non synthetic, natural medicines derived from plant sources due to better tolerance and minimum adverse drug reactions as compared to synthetic medicines. Herbal products are also commonly used by the patients with certain chronic medical conditions, including breast cancer, liver disease, human immunodeficiency, asthma and rheumatological disorders. WHO estimates that about three-quarters of the world's population currently uses herbs and other forms of traditional medicines for the treatment of various diseases. The herbs are formulated in different modern dosage forms, such as Tablets, Capsules, Topical cream, Gel, Ointment and even some novel drug delivery forms, like extended release, sustained release, and microencapsules dosage forms. Patenting of herbal formulations has increased over the past few years and scientific evidence of therapeutic activity has been reported by performing various in vitro and in vivo experiments. This manuscript deals with various patented herbal formulations with their therapeutic application against various diseases.

  17. Viability of lactobacillus acidophilus in various vaginal tablet formulations

    Directory of Open Access Journals (Sweden)

    Fazeli M.R.

    2006-07-01

    Full Text Available The lactobacilli which are present in vaginal fluids play an important role in prevention of vaginosis and there are considerable interests in formulation of these friendly bacteria into suitable pharmaceutical dosage forms. Formulating these microorganisms for vaginal application is a critical issue as the products should retain viability of lactobacilli during formulation and also storage. The aim of this study was to examine the viability and release of Lactobacillus acidophilus from slow-release vaginal tablets prepared by using six different retarding polymers and from two effervescent tablets prepared by using citric or adipic acid. The Carbomer–based formulations showed high initial viablility compared to those based on HPMC-LV, HPMC-HV, Polycarbophil and SCMC polymers which showed one log decrease in viable cells. All retarding polymers in slow release formulations presented a strong bacterial release at about 2 h except Carbomer polymers which showed to be poor bacterial releasers. Although effervescent formulations produced a quick bacterial release in comparison with polymer based slow-release tablets, they were less stable in cold storage. Due to the strong chelating characteristic of citric acid, the viability was quickly lost for aqueous medium of citric acid in comparison with adipic acid based effervescent tablets.

  18. FORMULATION AND EVALUATION OF GASTRORETENTIVE FLOATING TABLETS OF VENLAFAXINE HCl

    Directory of Open Access Journals (Sweden)

    P S Rajasekhar

    2012-12-01

    Full Text Available The purpose of the present investigation is to formulate gastroretentive floating tablets of Venlafaxine hydrochloride thus increasing its gastric residence time as well as bioavailability and therapeutic efficacy. Venlafaxine HCl having a short biological half-life of 4h is eliminated quickly from the body leading to low therapeutic efficacy. Therefore a sustained release medication was advantageous so as to achieve the prolonged therapeutic effect and to reduce peak and valley effect in plasma concentration. This can be circumvented by formulating modified gastro retentive sustained release dosage forms which resides in the stomach for sufficient time to release the drug in vicinity of the absorption zone. Nine formulations of Venlafaxine HCl tablets were formulated by hot melt extrusion technique (HME using three polymers like HPMC K15M, Xanthan gum and Guar gum in a various concentrations. Bees wax was used as a melting aid and sodium bicarbonate was used as a gas generating agent. The prepared tablets were evaluated for pre and post compression parameters, buoyancy time, floating lag time and in vitro dissolution study. In vitro dissolution study was carried out in pH 1.2 buffer. It had been found that increase in polymer concentration diminishes drug release profile. The in vitro cumulative % drug release of nine formulations ranged from 88.58 – 99.19 with more than 12h buoyancy. The in vitro drug release of optimised formulation followed Higuchi kinetics and the drug release mechanism was found to be non- fickian type.

  19. Explosive Formulation Pilot Plant

    Data.gov (United States)

    Federal Laboratory Consortium — The Pilot Plant for Explosive Formulation supports the development of new explosives that are comprised of several components. This system is particularly beneficial...

  20. Design, Development and Characterization of Extended Release Multiunit Particulate System of Anti-Inflammatory Drug

    Directory of Open Access Journals (Sweden)

    Dhiren Daslaniya

    2009-07-01

    Full Text Available Multi unit particulate system has long been employed to improve the bioavailability of drugs. Mesalamine pellets were prepared by Coating drug solution on sugar sphere followed by various functional coating. The influence of rate controlling membrane made up of Eudragit RSPO and Eudragit RLPO in combination with delay release polymer coating with Eudragit L100 in different proportions on drug release kinetics was studied. Pellets were for the various parameter like Physical characteristics, assay and in-vitro dissolution profile. The study confirmed that mesalamine can be delivered by multi unit particulate system into lower part of intestine. Optimized formulations were evaluated for In-vitro release profile. The optimized formula was stable at accelerated storage condition 40°C / 75 % RH. Prepared Pellets can be used in the treatment of the ulcerative colitis.

  1. Formulation Optimization and In-vitro Evaluation of Oral Floating ...

    African Journals Online (AJOL)

    forming agents for formulating controlled release floating tablets of captopril. FTIR and DSC spectra showed ..... correspond to the stretching vibrations of C–H bond and carboxyl .... barrier which produces upward motion and as a result tablets ...

  2. On delay-dependent robust stability of neutral systems

    Institute of Scientific and Technical Information of China (English)

    Renxin ZHONG; Zhi YANG; Guoli WANG

    2006-01-01

    The delay-dependent robust stability of uncertain linear neutral systems with delays is investigated. Both discrete-delay-dependent/neutral-delay-independent and neutral-/discrete- delay-dependent stability criteria will be developed. The proposed stability criteria are formulated in the form of linear matrix inequalities and it is easy to check the robust stability of the considered systems. By introducing certain Lyapunov-Krasovskii functional the mathematical development of our result avoids model transformation and bounding for cross terms, which lead to conservatism. Finally, numerical example is given to indicate the improvement over some existing results.

  3. Viability of lactobacillus acidophilus in various vaginal tablet formulations

    OpenAIRE

    Fazeli M.R.; Toliyat T.; Samadi N.; Hajjaran S.; Jamalifar H.

    2006-01-01

    The lactobacilli which are present in vaginal fluids play an important role in prevention of vaginosis and there are considerable interests in formulation of these friendly bacteria into suitable pharmaceutical dosage forms. Formulating these microorganisms for vaginal application is a critical issue as the products should retain viability of lactobacilli during formulation and also storage. The aim of this study was to examine the viability and release of Lactobacillus acidophilus from slow-...

  4. Formulation and Evaluation of Aceclofenac Loaded Cubosomal Topical Gel

    Directory of Open Access Journals (Sweden)

    K. Bhargavi

    2015-11-01

    Full Text Available The aim of present work was to formulate and evaluate sustained release formulation of Aceclofenac a Non -steroidal anti-inflammatory drug (NSAID, as cubosomal topical gel to reduce gastro intestinal effects and to improve the bioavailability of the drug. Different formulations of Aceclofenac cubosomes were prepared by Top down approach using GMO as lipid phase vehicle, Poloxamer 407 as stabilizer and distilled water as aqueous phase by varying the concentrations of GMO and Poloxamer 407. Resultant formulations were characterized for particle size, zeta potential, surface morphology, encapsulation efficiency and in-vitro drug release. Optimized formulation (F10 showed drug release of 83.25% in 8hours. Aceclofenac cubosomal gel was prepared by using optimized cubosomal formulation (F10, Carbopol 940,Carbopol 934, HPMC K4M and HPMC 15M.Gels were evaluated for pH, viscosity, drug content and in-vitro drug diffusion studies. Among all the preparations, formulation G2 was found to show entrapment efficiency of 96.85 and in vitro drug release of 78.5%. Ex-vivo permeation of optimized gel formulation (D2 was evaluated across rat epidermis.

  5. Formulations in first encounters

    NARCIS (Netherlands)

    A. Hak (Tony); F. de Boer (Fijgje)

    1994-01-01

    markdownabstractThe paper describes and compares the use and function of the formulation--decision pair in three types of diagnostic interviewing. The investigatory type of interviewing, which typically occurs in the medical interview, is characterized by the absence of formulations. In the explora

  6. Oral suspensions of morphine hydrochloride for controlled release: rheological properties and drug release.

    Science.gov (United States)

    Morales, M E; López, G; Gallardo, V; Ruiz, M A

    2011-04-04

    Recent developments in pharmaceutical technology have facilitated the design and production of modified release formulas for drugs whose physical, chemical or biological properties impede release and thus might compromise their efficacy or safety. One such drug is morphine, whose short half-life requires repeated doses at short intervals. The use of biocompatible polymers such as ethylcellulose has made it possible to develop microencapsulated formulations which facilitate liquid, sustained-release pharmaceutical formulas for oral administration. We developed a stable final formulation of morphine with an acceptable release profile by comparing the rheological properties and stability of formulations with different thickeners (xanthan gum, Carbopol, and carboxymethylcellulose with microcrystalline cellulose) at different concentrations from 0.25% to 1.0%. Release assays in a Franz-type cell were done to determine the most suitable release profile for the formulation.