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Sample records for controlled release formulations

  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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...

  9. 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.

  10. 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...

  11. 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...

  12. 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.

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

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    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.

  14. 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.

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

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    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.

  16. 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

  17. Controlled-Release Personal Use Arthropod Repellent Formulation

    Science.gov (United States)

    1985-09-25

    deodorant , or other cosmetic enhancers, and rinsed with 70% ethanol. For each subject control site, (5 cm in diameter), anG two test sites, 6 x 16.7 cm...Camouflage 0-1 c) Polyurethane Rifle Stocks 51 Metals S-1 a) Aluminum General Equipeent 6) Natural Products -- I a) Leather Boots 7) Textiles T-1 a...The area was slightly tacky to touch and a definite loss of gloss was noted. * e. metals Aluminum was not visibly affected by all three solutions. f

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

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    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.

  19. 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.

  20. 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.

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

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    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.

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

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    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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  12. 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

  13. 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

  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. 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.

  16. 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.

  17. 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...

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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,.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

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

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    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.

  12. 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.

  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. 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.

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

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    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

  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. "Sustained release formulation of Metoclopramide Hydrochloride "

    Directory of Open Access Journals (Sweden)

    Dabbagh MA

    2000-08-01

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

  18. 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

  19. 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.

  20. 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

  1. 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.

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

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    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.

  3. 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.

  4. 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

  5. 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.

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

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    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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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

  13. 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.

  14. 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.

  15. 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.

  16. Formulation and Dissolution Study of Valsartan Immediate Release Tablets

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    Baskara Haripriya

    2013-02-01

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

  18. Formulation and Evaluation of Nateglinide Sustained Release Tablets

    Directory of Open Access Journals (Sweden)

    Sridevi Gowripattapu

    2016-01-01

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

  19. 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.

  20. 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.

  1. FORMULATION AND EVALUATION OF NIFEDIPINE SUSTAINED RELEASE PELLETS

    Directory of Open Access Journals (Sweden)

    T Akelesh

    2011-08-01

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

  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

    Directory of Open Access Journals (Sweden)

    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

    Directory of Open Access Journals (Sweden)

    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

    Directory of Open Access Journals (Sweden)

    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 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  8. 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.

  9. Controlled-release microchips.

    Science.gov (United States)

    Sharma, Sadhana; Nijdam, A Jasper; Sinha, Piyush M; Walczak, Robbie J; Liu, Xuewu; Cheng, Mark M-C; Ferrari, Mauro

    2006-05-01

    Efficient drug delivery remains an important challenge in medicine: continuous release of therapeutic agents over extended time periods in accordance with a predetermined temporal profile; local delivery at a constant rate to the tumour microenvironment to overcome much of the systemic toxicity and to improve antitumour efficacy; improved ease of administration, and increasing patient compliance required are some of the unmet needs of the present drug delivery technology. Microfabrication technology has enabled the development of novel controlled-release microchips with capabilities not present in the current treatment modalities. In this review, the current status and future prospects of different types of controlled-release microchips are summarised and analysed with reference to microneedle-based microchips, as well as providing an in-depth focus on microreservoir-based and nanoporous microchips.

  10. 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.

  11. 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...

  12. 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.

  13. 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

  14. [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

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

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    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.

  16. 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.

  17. 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.

  18. Free boundary problems in controlled release pharmaceuticals: II. swelling-controlled release

    OpenAIRE

    Cohen, Donald S.; Erneux, Thomas

    1988-01-01

    A problem in controlled release pharmaceutical systems is formulated and studied. The device modeled is a polymer matrix containing an initially immobilized drug. The release of the drug is achieved by countercurrent diffusion through a penetrant solvent with the release rate being determined by the rate of diffusion of the solvent in the polymer. The mathematical theory yields a free boundary problem which is studied in various asymptotic regimes.

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

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    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.

  20. Bioavailability of immediate and controlled release formulations of lithium carbonate Biodisponibilidade de formulações de liberação imediata e controlada de carbonato de lítio

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    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

  1. FORMULATION AND EVALUATION OF BACLOFEN CONTROLLED POROSITY OSMOTIC PUMP TABLETS

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    Indarapu Rajendra Prasad

    2013-06-01

    Full Text Available In the present study, attempts were made to develop and evaluate the controlled porosity osmotic pump (CPOP based drug delivery system of sparingly water soluble drug Baclofen. Formulation variables, such as, levels of solubility enhancer, ratio of drug to osmogents, coat thickness of semi permeable membrane (SPM and level of pore former were found to affect the drug release from the developed formulations. Cellulose acetate was used as the semi permeable membrane. Drug release was directly proportional to the level of the solubility enhancer, osmotic pressure generated by osmotic agent and level of pore former; however, was inversely proportional to the coat thickness of SPM. Drug release from developed formulations was independent of pH and agitation intensities of release media. Burst strength of the exhausted shells decreased with increase in the level of pore former. This system was found to deliver Baclofen at a zero-order rate. The optimized formulations were subjected to stability studies as per ICH guidelines, and formulations were found to be stable after 45days study.

  2. 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.

  3. Controlled Release of Imidacloprid from Poly Styrene-Diacetone - Nanoformulation

    Science.gov (United States)

    Qian, Kun; Guo, Yanzhen; He, Lin

    2012-01-01

    Imidacloprid is a neonicotinoids insecticide, which is important for the cash crops such as tomato, rape and so on. The conventional formulation does not only increase the loss of pesticide but also leads to environmental pollution. Controlled-release formulations of pesticide are highly desirable not only for attaining the most effective utilization of the pesticide, but also for reducing environmental pollution. Pesticide imidacloprid was incorporated in poly (styrene-diacetone crylamide)-based formulation to obtain controlled release properties, and the imidacloprid nanocontrolled release formulation was characterized by infrared (IR) and field emission scanning electron microscope (FESEM). Factors related to loading efficiency, swelling and release behaviors of the formulation were investigated. It showed that the loading efficiency could reach about 40% (w/w). The values for the diffusion exponent "n" were in the range of 0.31-0.58, which indicated that the release of imidacloprid was diffusion-controlled. The time taken for 50% of the active ingredient to be released into water, T50, was also calculated for the comparison of formulations in different conditions. The results showed that the formulation with higher temperature and more diacetone crylamide had lower value of T50, which means a quicker release of the active ingredient. This study highlighted some pieces of evidence that improved pesticide incorporation and slower release were linked to potential interactions between the pesticide and the polymer.

  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. 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

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

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    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.

  7. 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.

  8. Workload Control with Continuous Release

    NARCIS (Netherlands)

    Phan, B. S. Nguyen; Land, M. J.; Gaalman, G. J. C.

    2009-01-01

    Workload Control (WLC) is a production planning and control concept which is suitable for the needs of make-to-order job shops. Release decisions based on the workload norms form the core of the concept. This paper develops continuous time WLC release variants and investigates their due date

  9. Birth control - slow release methods

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/007555.htm Birth control - slow release methods To use the sharing features on this page, please enable JavaScript. Certain birth control methods contain man-made forms of hormones. These ...

  10. 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.

  11. 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.

  12. 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

  13. 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

  14. Optogenetic control of ATP release

    Science.gov (United States)

    Lewis, Matthew A.; Joshi, Bipin; Gu, Ling; Feranchak, Andrew; Mohanty, Samarendra K.

    2013-03-01

    Controlled release of ATP can be used for understanding extracellular purinergic signaling. While coarse mechanical forces and hypotonic stimulation have been utilized in the past to initiate ATP release from cells, these methods are neither spatially accurate nor temporally precise. Further, these methods cannot be utilized in a highly effective cell-specific manner. To mitigate the uncertainties regarding cellular-specificity and spatio-temporal release of ATP, we herein demonstrate use of optogenetics for ATP release. ATP release in response to optogenetic stimulation was monitored by Luciferin-Luciferase assay (North American firefly, photinus pyralis) using luminometer as well as mesoscopic bioluminescence imaging. Our result demonstrates repetitive release of ATP subsequent to optogenetic stimulation. It is thus feasible that purinergic signaling can be directly detected via imaging if the stimulus can be confined to single cell or in a spatially-defined group of cells. This study opens up new avenue to interrogate the mechanisms of purinergic signaling.

  15. 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

  16. 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.

  17. Controlled release from recombinant polymers.

    Science.gov (United States)

    Price, Robert; Poursaid, Azadeh; Ghandehari, Hamidreza

    2014-09-28

    Recombinant polymers provide a high degree of molecular definition for correlating structure with function in controlled release. The wide array of amino acids available as building blocks for these materials lend many advantages including biorecognition, biodegradability, potential biocompatibility, and control over mechanical properties among other attributes. Genetic engineering and DNA manipulation techniques enable the optimization of structure for precise control over spatial and temporal release. Unlike the majority of chemical synthetic strategies used, recombinant DNA technology has allowed for the production of monodisperse polymers with specifically defined sequences. Several classes of recombinant polymers have been used for controlled drug delivery. These include, but are not limited to, elastin-like, silk-like, and silk-elastinlike proteins, as well as emerging cationic polymers for gene delivery. In this article, progress and prospects of recombinant polymers used in controlled release will be reviewed.

  18. Meticulous Overview on the Controlled Release Fertilizers

    Directory of Open Access Journals (Sweden)

    Siafu Ibahati Sempeho

    2014-01-01

    Full Text Available Owing to the high demand for fertilizer formulations that will exhaust the possibilities of nutrient use efficiency (NUE, regulate fertilizer consumption, and lessen agrophysicochemical properties and environmental adverse effects instigated by conventional nutrient supply to crops, this review recapitulates controlled release fertilizers (CRFs as a cutting-edge and safe way to supply crops’ nutrients over the conventional ways. Essentially, CRFs entail fertilizer particles intercalated within excipients aiming at reducing the frequency of fertilizer application thereby abating potential adverse effects linked with conventional fertilizer use. Application of nanotechnology and materials engineering in agriculture particularly in the design of CRFs, the distinctions and classification of CRFs, and the economical, agronomical, and environmental aspects of CRFs has been revised putting into account the development and synthesis of CRFs, laboratory CRFs syntheses and testing, and both linear and sigmoid release features of CRF formulations. Methodical account on the mechanism of nutrient release centring on the empirical and mechanistic approaches of predicting nutrient release is given in view of selected mathematical models. Compositions and laboratory preparations of CRFs basing on in situ and graft polymerization are provided alongside the physical methods used in CRFs encapsulation, with an emphasis on the natural polymers, modified clays, and superabsorbent nanocomposite excipients.

  19. 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.

  20. 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.

  1. 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.

  2. Abuse deterrent formulations and the Controlled Substances Act (CSA).

    Science.gov (United States)

    Sapienza, Frank L

    2006-06-01

    The Controlled Substances Act (CSA) has reduced the diversion of controlled substances at the manufacturing and distribution levels. Recent increased diversion has occurred at the retail level. Levels of diversion and abuse of controlled substances with similar abuse potential and therapeutic indications often parallel availability for medical use, while rates of diversion and abuse may be influenced by factors related to specific products, including their formulations and risk management plans. Abuse deterrent formulations may reduce abuse and attendant adverse health consequences even if the products are diverted. Their development should consider how, to what extent and by whom products containing the targeted substance are abused. It should take into consideration all potential types of abuse including "as is", multiple doses, alternate routes of administration, physical or chemical separation of the active ingredient, compromised extended release mechanisms and abuse in combination with other substances. Industry incentives for developing abuse-resistant formulations include enhanced corporate image and potentially less restrictive scheduling or risk management plans. Scheduling is substance specific, but the CSA includes products/formulations that are differentially scheduled. Issues to be considered for differential scheduling under the CSA include: (1) whether there is legal authority to do so; (2) application of standard scheduling criteria to individual products; (3) product specific data for "eight factor analyses"; (4) development of predictive data and standards accepted by the scientific and regulatory communities; (5) use of predictive data or post marketing surveillance data; (6) international treaty obligations. These issues must be addressed before differential scheduling can be considered.

  3. DEVELOPMENT AND EVALUATION OF CLOZAPINE PELLETS FOR CONTROLLED RELEASE

    Directory of Open Access Journals (Sweden)

    D.V. Gowda

    2012-08-01

    Full Text Available This research work was done to design oral controlled release matrix pellets of water insoluble drug Clozapine, using blend of Hydroxypropyl cellulose and glyceryl palmito stearate as as matrix polymers, methyl crystalline cellulose as spheronizer enhancer,sodium lauryl sulphate as pore forming agent. Clozapine formulations developed by the pellitization technique by drug loaded pellets were characterized with regard to the drug content, size distribution, Scanning electron microscopy, differential scanning calorimetry, fourier transform infrared spectroscopy and Xray Diffraction study. Stability studies were carried out on the optimized formulation for aperiod of 90 days, 40 ± 2 oC and 75 ± 5% relative humidity. The drug content was in the range of 95.34 – 98.12 %. The mean particle size of drug loaded pellets was in the range 1018 to 1065 mm. SEM photographs and calculated sphericity factor confirms that the prepared formulations were spherical in nature. The drug loaded pellets were stable and compatible as confirmed by DSC and FTIR studies. XRD patterns revealed the crystalline nature of pure clozapine. Loose surface crystal study indicated that crystalline clozapine was observed in all formulation and more clear in formulation A5. Higher amount of clozapine released was observed from formulation A5 and Syclop® 25 mg tablet as compared to all other formulations and mechanism of drug release followed Fickian diffusion. It can be concluded that formulation A5 is an ideal formulation for once a day administration.

  4. 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.

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

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    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.

  6. 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.

  7. Application of advanced polymeric materials for controlled release pesticides

    Science.gov (United States)

    Rahim, M.; Hakim, M. R.; Haris, H. M.

    2016-08-01

    The objective of this work was to study the capability of advanced polymeric material constituted by chitosan and natural rubber matrices for controlled release of pesticides (1-hydroxynaphthalene and 2-hydroxynaphthalene) in aqueous solution. The released amount of pesticides was measured spectrophotometrically from the absorbance spectra applying a standardized curve. The release of the pesticides was studied into refreshing and non-refreshing neutral aqueous media. Interestingly, formulation successfully indicated a consistent, controlled and prolonged release of pesticides over a period of 35 days.

  8. Preparation and evaluation of controlled release tablets of carvedilol

    Directory of Open Access Journals (Sweden)

    Varahala Setti M

    2009-01-01

    Full Text Available The objective of the present investigation is to design and evaluate controlled release tablets of carvedilol, employing synthetic polymers like polyethylene oxides, of different molecular weights as release retarding materials and to select the optimized formulation based on the pharmacokinetics of carvedilol. Matrix tablets each containing 80 mg of carvedilol were formulated employing PEO N60 K, PEO 301, and PEO 303 as release-retarding polymers and β Cyclodextrin and HP β cyclodextrin as release modulators from the matrix. Carvedilol release from the formulated tablets was very slow. Hence the release was modulated with the use of cyclodextrins. The dissolution from the matrix tablets was spread over more than 24 hours and depended on the type of polymer, its concentration and the type of cyclodextrin used. All the matrix tablets prepared using polyethylene oxides showed very good controlled release over more than 24 hours. The matrix tablets prepared using HP β cyclodextrin showed a higher dissolution rate and gave a dissolution profile that was comparable to the theoretical sustained release needed for once-a-day administration of carvedilol. The drug release mechanism from the matrix tablets was found to be quasi Fickian mechanism.

  9. Development of controlled release tablet by optimizing HPMC: consideration of theoretical release and RSM.

    Science.gov (United States)

    Pani, Nihar R; Nath, Lila K

    2014-04-15

    The objective of the study was to develop controlled release tablets of nateglinide, a meglitinide derivative anti-diabetic drug, considering theoretical release profile and response surface methodology (RSM). 3(2) factorial design was utilized to optimize concentration of hydroxylpropylmethylcellulose (HPMC) K15M and K100M to obtain the desired responses (drug release at one and six hours). Theoretical release profile of drug for controlled release formulation was calculated and considered as reference for the determination of similarity factor (f2) and desimilarity factor (f1). RSM, f2 and f1 were used to select the optimum formulation. Formulation containing HPMC K15M (5%) and HPMC K100M (15%) was found optimum with desired responses with f2=86.05 and drug release profile followed zero order kinetics. Excipients used were compatible with drug, confirmed initially through DSC and IST study. The optimization of experiments was validated and optimum formulation was passed the stability study. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. 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.

  11. 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

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. A retrospective mathematical analysis of controlled release design and experimentation.

    Science.gov (United States)

    Rothstein, Sam N; Kay, Jennifer E; Schopfer, Francisco J; Freeman, Bruce A; Little, Steven R

    2012-11-01

    The development and performance evaluation of new biodegradable polymer controlled release formulations relies on successful interpretation and evaluation of in vitro release data. However, depending upon the extent of empirical characterization, release data may be open to more than one qualitative interpretation. In this work, a predictive model for release from degradable polymer matrices was applied to a number of published release data in order to extend the characterization of release behavior. Where possible, the model was also used to interpolate and extrapolate upon collected released data to clarify the overall duration of release and also kinetics of release between widely spaced data points. In each case examined, mathematical predictions of release coincide well with experimental results, offering a more definitive description of each formulation's performance than was previously available. This information may prove particularly helpful in the design of future studies, such as when calculating proper dosing levels or determining experimental end points in order to more comprehensively evaluate a controlled release system's performance.

  17. 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.

  18. 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.

  19. 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.

  20. 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

  1. 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.

  2. 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.

  3. 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.

  4. Modelling and simulations of controlled release fertilizer

    Science.gov (United States)

    Irfan, Sayed Ameenuddin; Razali, Radzuan; Shaari, Ku Zilati Ku; Mansor, Nurlidia

    2016-11-01

    The recent advancement in controlled release fertilizer has provided an alternative solution to the conventional urea, controlled release fertilizer has a good plant nutrient uptake they are environment friendly. To have an optimum plant intake of nutrients from controlled release fertilizer it is very essential to understand the release characteristics. A mathematical model is developed to predict the release characteristics from polymer coated granule. Numerical simulations are performed by varying the parameters radius of granule, soil water content and soil porosity to study their effect on fertilizer release. Understanding these parameters helps in the better design and improve the efficiency of controlled release fertilizer.

  5. 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.

  6. 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.

  7. 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...

  8. 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.

  9. 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...

  10. 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.

  11. 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.

  12. 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.

  13. 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,

  14. 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...

  15. 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

  16. 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...

  17. 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...

  18. 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.

  19. 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

  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

    Directory of Open Access Journals (Sweden)

    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. 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

  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 evaluation of modified-release effervescent floating tablets of ofloxacin

    Directory of Open Access Journals (Sweden)

    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.

  5. FORMULATION AND EVALUATION OF CONTROLLED POROSITY OSMOTIC DRUG DELIVERY SYSTEM OF METOPROLOL SUCCINATE

    Directory of Open Access Journals (Sweden)

    Hardik Patel* and M. M. Patel

    2012-06-01

    Full Text Available Controlled porosity osmotic tablet of metoprolol succinate prepared and evaluated in this study. Metoprolol succinate is very high soluble drug, so complete drug release obtained very fast. It is difficult to formulate osmotic tablet of Metoprolol succinate which gives drug release up to 24 hr at zero order. To get desired dissolution profile various formulation parameters like osmogen concentration, level of weight gain and level of pore former concentration were studied. Hypromellose was added as release retardant to reduce its dissolution rate and get drug release up to 24 hr at zero order. As concentration of release retardant increases, dissolution rate decreases. Final optimized formulation with hypromellose was studied for effect of pH of dissolution media, agitation intensity and osmotic pressure of dissolution media. There is no effect of above variables on dissolution confirms that prepared metoprolol succinate tablet gives drug release with osmotic mechanism. Final optimized formulation complies with the USP criteria for the dissolution of metoprolol succinate extended release tablet.

  6. 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

  7. 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

  8. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    C Kumaresan

    2016-01-01

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

  11. 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.

  12. Formulation development and evaluation of controlled porosity osmotic pump delivery system for oral delivery of atenolol

    Directory of Open Access Journals (Sweden)

    Garvendra S Rathore

    2012-01-01

    Full Text Available In the present study, we developed and evaluated the controlled porosity osmotic pump (CPOP based drug delivery system of sparingly water soluble drug atenolol (ATL. We selected target release profile and optimized different variables to help us achieve this. Formulation variables, such as, the levels of solubility enhancer (0-15% w/w of drug, ratio of the drug to the osmogents, coat thickness of the semipermeable membrane (SPM and level of pore former (0-20% w/w of polymer were found to effect the drug release from the developed formulations. Cellulose acetate (CA 398-10 was used as the semipermeable membrane containing polyethylene glycol 400 as the Cplasticizer. ATL release was directly proportional to the level of the solubility enhancer, osmotic pressure generated by osmotic agent and level of pore former; however, was inversely proportional to the coat thickness of SPM. Drug release from developed formulations was independent of the pH and agitation intensities of release media. Burst strength of the exhausted shells decreased with increase in the level of pore former. The optimized formulations were subjected to stability studies as per International Conference on Harmonisation (ICH guidelines, and formulations were found to be stable after 3 months study. Steady-state plasma levels of drug were predicted by the method of superposition.

  13. 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.

  14. 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.

  15. Recent patents in flavor controlled release.

    Science.gov (United States)

    Feng, Tao; Xiao, Zuobing; Tian, Huaixiang

    2010-06-01

    In recent years, considerable effort has been directed toward the preparation of flavoring materials specifically, flavor materials have been sought that provide greater flavor intensity coupled with controlled flavor release for long periods of time. Here, some recent patents related to controlled flavor release are reviewed from the angle of its application field, its mechanism and its determination method. It is found that controlled flavor release often depends not only on materials' chemical and physical properties, such as melting point, solution properties and so on, but also on flavors' chemical and physical properties, such as diffusion capacity, its stability in different media etc. Meanwhile, flavor release is also controlled by an electric reducing device according to the flavor generation condition. It might be also known that flavor release rate could be determined by using a purge-and-trap/gas chromatographic procedure. In future, it's necessary to use mathematical model to study the kinetic behavior of controlled flavor release.

  16. Design and characterization of controlled release tablet of metoprolol

    Directory of Open Access Journals (Sweden)

    Gautam Singhvi

    2012-01-01

    Full Text Available Metoprolol succinate is a selective beta-adrenergic receptor blocker useful in treatment of hypertension, angina and heart failure. The purpose of the present work was to design and evaluate controlled release matrix type tablet of Metoprolo succinate using HPMC K15M and Eudragit (RLPO and RSPO as a matrix forming agents. Effect of various polymer alone and combinations were studied in pH 1.2 buffer using USP type II paddle at 50 rpm. HPMC was used to form firm gel with Eudragit polymer. Formulation with Equal proportion (1:1 of Eudragit RSPO and RLPO showed optimum drug release t50 =7 hrs and t100 =16 hrs indicate optimum permeability for drug release from matrix. The drug release mechanism was predominantly found to be Non-Fickian diffusion controlled.

  17. Stimuli responsive nanomaterials for controlled release applications

    KAUST Repository

    Li, Song

    2012-01-01

    The controlled release of therapeutics has been one of the major challenges for scientists and engineers during the past three decades. Coupled with excellent biocompatibility profiles, various nanomaterials have showed great promise for biomedical applications. Stimuli-responsive nanomaterials guarantee the controlled release of cargo to a given location, at a specific time, and with an accurate amount. In this review, we have combined the major stimuli that are currently used to achieve the ultimate goal of controlled and targeted release by "smart" nanomaterials. The most heavily explored strategies include (1) pH, (2) enzymes, (3) redox, (4) magnetic, and (5) light-triggered release.

  18. 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)

  19. Assembly of bio-nanoparticles for double controlled drug release.

    Directory of Open Access Journals (Sweden)

    Wei Huang

    Full Text Available A critical limiting factor of chemotherapy is the unacceptably high toxicity. The use of nanoparticle based drug carriers has significantly reduced the side effects and facilitated the delivery of drugs. Source of the remaining side effect includes (1 the broad final in vivo distribution of the administrated nanoparticles, and (2 strong basal drug release from nanoparticles before they could reach the tumor. Despite the advances in pH-triggered release, undesirable basal drug release has been a constant challenge under in vivo conditions. In this study, functionalized single walled carbon nanohorn supported immunoliposomes were assembled for paclitaxel delivery. The immunoliposomes were formulated with polyethylene glycol, thermal stable and pH sensitive phospholipids. Each nanohorn was found to be encapsulated within one immunoliposome. Results showed a highly pH dependent release of paclitaxel in the presence of serum at body temperature with minimal basal release under physiological conditions. Upon acidification, paclitaxel was released at a steady rate over 30 days with a cumulative release of 90% of the loaded drug. The drug release results proved our hypothesized double controlled release mechanism from the nanoparticles. Other results showed the nanoparticles have doubled loading capacity compared to that of traditional liposomes and higher affinity to breast cancer cells overexpressing Her2 receptors. Internalized nanoparticles were found in lysosomes.

  20. Lignin based controlled release coatings

    NARCIS (Netherlands)

    Mulder, W.J.; Gosselink, R.J.A.; Vingerhoeds, M.H.; Harmsen, P.F.H.; Eastham, D.

    2011-01-01

    Urea is a commonly used fertilizer. Due to its high water-solubility, misuse easily leads to excess nitrogen levels in the soil. The aim of this research was to develop an economically feasible and biodegradable slow-release coating for urea. For this purpose, lignin was selected as coating material

  1. Lignin based controlled release coatings

    NARCIS (Netherlands)

    Mulder, W.J.; Gosselink, R.J.A.; Vingerhoeds, M.H.; Harmsen, P.F.H.; Eastham, D.

    2011-01-01

    Urea is a commonly used fertilizer. Due to its high water-solubility, misuse easily leads to excess nitrogen levels in the soil. The aim of this research was to develop an economically feasible and biodegradable slow-release coating for urea. For this purpose, lignin was selected as coating

  2. Lignin based controlled release coatings

    NARCIS (Netherlands)

    Mulder, W.J.; Gosselink, R.J.A.; Vingerhoeds, M.H.; Harmsen, P.F.H.; Eastham, D.

    2011-01-01

    Urea is a commonly used fertilizer. Due to its high water-solubility, misuse easily leads to excess nitrogen levels in the soil. The aim of this research was to develop an economically feasible and biodegradable slow-release coating for urea. For this purpose, lignin was selected as coating material

  3. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  5. 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.

  6. 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.

  7. 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.

  8. Controlled release of chlorhexidine from UDMA-TEGDMA resin.

    Science.gov (United States)

    Anusavice, K J; Zhang, N-Z; Shen, C

    2006-10-01

    Chlorhexidine salts are available in various formulations for dental applications. This study tested the hypothesis that the release of chlorhexidine from a urethane dimethacrylate and triethylene glycol dimethacrylate resin system can be effectively controlled by the chlorhexidine diacetate content and pH. The filler concentrations were 9.1, 23.1, or 33.3 wt%, and the filled resins were exposed to pH 4 and pH 6 acetate buffers. The results showed that Fickian diffusion was the dominant release mechanism. The rates of release were significantly higher in pH 4 buffer, which was attributed to the increase of chlorhexidine diacetate solubility at lower pH. The higher level of filler loading reduced the degree of polymerization, leading to a greater loss of organic components and higher chlorhexidine release rates.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. Modeling controlled nutrient release from polymer coated fertilizers: diffusion release from single granules.

    Science.gov (United States)

    Shaviv, Avi; Raban, Smadar; Zaidel, Elina

    2003-05-15

    A comprehensive model describing the complex and "non-Fickian" (mathematically nonlinear) nature of the release from single granules of membrane coated, controlled release fertilizers (CRFs) is proposed consisting of three stages: i. a lag period during which water penetrates the coating of the granule dissolving part of the solid fertilizer in it ii. a period of linear release during which water penetration into and release out occur concomitantly while the total volume of the granules remains practically constant; and iii. a period of "decaying release", starting as the concentration inside the granule starts to decrease. A mathematical model was developed based on vapor and nutrient diffusion equations. The model predicts the release stages in terms of measurable geometrical and chemophysical parameters such as the following: the product of granule radius and coating thickness, water and solute permeability, saturation concentration of the fertilizer, and its density. The model successfully predicts the complex and "sigmoidal" pattern of release that is essential for matching plant temporal demand to ensure high agronomic and environmental effectiveness. It also lends itself to more complex statistical formulations which account for the large variability within large populations of coated CRFs and can serve for further improving CRF production and performance.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  19. A Bayesian Formulation of Behavioral Control

    Science.gov (United States)

    Huys, Quentin J. M.; Dayan, Peter

    2009-01-01

    Helplessness, a belief that the world is not subject to behavioral control, has long been central to our understanding of depression, and has influenced cognitive theories, animal models and behavioral treatments. However, despite its importance, there is no fully accepted definition of helplessness or behavioral control in psychology or…

  20. 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.

  1. Release Control of Dye from Agar Ball

    OpenAIRE

    板屋, 智之; 山村, 俊貴; 唐澤, 有太朗

    2013-01-01

    Agar is a special product of Nagano prefecture. To utilize agar gel as adsorbing or releasing material of dyes or drugs, spherical agar gel “agar ball” was prepared by dropping aqueous agar solution into salad oil. And releasing behavior of a dye (rhodamine B) from agar ball was studied. The dye is released easily from agar ball, but the release can be controlled by hybiridazation of agar and galatin. In addition, it was found that agar ball could extract the dye from oil phase containing the...

  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. Rosin and rosin derivatives as hydrophobic matrix materials for controlled release of drugs.

    Science.gov (United States)

    Pathak, Y V; Dorle, A K

    1990-09-01

    The evaluation of rosin, a rosin hard paraffin adduct, and four rosin esters as hydrophobic matrix materials for the controlled release of drugs is reported, using aspirin as a drug model. Aspirin matrix tablets were prepared using a wet granulation (nonaqueous) method, and were evaluated for various pharmaceutical parameters. Dissolution studies in pH 7.2 phosphate buffer showed that all formulations had hardness greater than 6 kg/cm2 and disintegration time greater than 150 min. Release of aspirin from the formulations obeyed a diffusion controlled first order kinetic and linear to the square root of time function. Two of the resin ester formulations had a T80% of more than 4 hr. The results suggest that these esters may find application in the development of sustained release formulations for the local treatment of dental diseases, or--as tablet matrices suitably coated with acid resistant material--in the development of oral sustained release drug delivery systems.

  4. Formulation and evaluation of controlled porosity osmotic pump for oral delivery of ketorolac.

    Science.gov (United States)

    Dasankoppa, Fatima Sanjeri; Ningangowdar, Mahesh; Sholapur, Hasanpasha

    2012-12-01

    The osmotic drug delivery systems suitable for oral administration typically consist of a compressed tablet core that is coated with a semipermeable membrane that has an orifice drilled on it by means of a laser beam or mechanical drill. Ketorolac is a nonsteroidal agent with powerful analgesic. Oral bioavailability of ketorolac was reported to be 90% with very low hepatic first-pass elimination; the biological half-life of 4-6 hours requires frequent administration to maintain the therapeutic effect. The aim of the current study was to design a controlled porosity osmotic pump (CPOP)based drug delivery system for controlled release of an NSAID agent, ketorolac tromethamine, which is expected to improve patient compliance due to reduced frequency; it also eliminates the need for complicated and expensive laser drilling and maintain continuous therapeutic concentration. The CPOP was designed containing pore-forming water-soluble additives in the coating membrane, which after coming in contact with water, dissolve, resulting in an in situ formation of a micro porous structure. The effect of different formulation variables, namely level of pore former (PVP), plasticizer (dibutyl phthalate) in the membrane, and membrane weight gain were studied. Drug release was inversely proportional to the membrane weight but directly related to the initial concentration of pore former (PVP) in the membrane. Drug release was independent of pH and agitational intensity, but dependent on the osmotic pressure of the release media. Based on the in vitro dissolution profile, formulation F3C1 (containing 0.5 g PVP and 1 g dibutyl phthalate in coating membrane) exhibited Peppas kinetic with Fickian diffusion-controlled release mechanism with a drug release of 93.67% in 12 hours and hence it was selected as optimized formulation. SEM studies showed the formation of pores in the membrane. The formulations were stable after 3 months of accelerated stability studies. CPOP was designed for

  5. 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.

  6. 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.

  7. Sintering of wax for controlling release from pellets.

    Science.gov (United States)

    Singh, Reena; Poddar, S S; Chivate, Amit

    2007-09-14

    The purpose of the present study was to investigate incorporation of hydrophobic (ie, waxy) material into pellets using a thermal sintering technique and to evaluate the pellets in vitro for controlled release. Pellets prepared by extrusion-spheronization technology were formulated with a water-soluble drug, microcrystalline cellulose, and carnauba wax. Powdered carnauba wax (4%-20%) prepared by grinding or by emulsification was studied with an attempt to retard the drug release. The inclusion of ground or emulsified carnauba wax did not sustain the release of theophylline for more than 3 hours. Matrix pellets of theophylline prepared with various concentrations of carnauba wax were sintered thermally at various times and temperatures. In vitro drug release profiles indicated an increase in drug release retardation with increasing carnauba wax concentration. Pellets prepared with ground wax showed a higher standard deviation than did those prepared with emulsified wax. There was incomplete release at the end of 12 hours for pellets prepared with 20% ground or emulsified wax. The sintering temperature and duration were optimized to allow for a sustained release lasting at least 12 hours. The optimized temperature and duration were found to be 100 degrees C and 140 seconds, respectively. The sintered pellets had a higher hydrophobicity than did the unsintered pellets. Scanning electron micrographs indicated that the carnauba wax moved internally, thereby increasing the surface area of wax within the pellets.

  8. A formulation to encapsulate nootkatone for tick control.

    Science.gov (United States)

    Behle, Robert W; Flor-Weiler, Lina B; Bharadwaj, Anuja; Stafford, Kirby C

    2011-11-01

    Nootkatone is a component of grapefruit oil that is toxic to the disease-vectoring tick, Ixodes scapularis Say, but unfortunately causes phytotoxicity to treated plants and has a short residual activity due to volatility. We prepared a lignin-encapsulated nootkatone formulation to compare with a previously used emulsifiable formulation for volatility, plant phytotoxicity, and toxicity to unfed nymphs of I. scapularis. Volatility of nootkatone was measured directly by trapping nootkatone vapor in a closed system and indirectly by measuring nootkatone residue on treated filter paper after exposure to simulated sunlight (Xenon). After 24 h in the closed system, traps collected only 15% of the nootkatone applied as the encapsulated formulation compared with 40% applied as the emulsifiable formulation. After a 1-h light exposure, the encapsulated formulation retained 92% of the nootkatone concentration compared with only 26% retained by the emulsifiable formulation. For plant phytotoxicity, cabbage, Brassica oleracea L., leaves treated with the encapsulated formulation expressed less necrosis, retaining greater leaf weight compared with leaves treated with the emusifiable formulation. The nootkatone in the emulsifiable formulation was absorbed by cabbage and oat, Avena sativa L., plants (41 and 60% recovered 2 h after application, respectively), as opposed to 100% recovery from the plants treated with encapsulated nootkatone. Using a treated vial technique, encapsulated nootkatone was significantly more toxic to I. scapularis nymphs (LC50 = 20 ng/cm2) compared with toxicity of the emulsifiable formulation (LC50 = 35 ng/cm2). Thus, the encapsulation of nootkatone improved toxicity for tick control, reduced nootkatone volatility, and reduced plant phytotoxicity.

  9. Formulation and evaluation of starch acetate matrix tablets in combination with surfactants for controlled release”

    Directory of Open Access Journals (Sweden)

    Mahesh Kumar Vishwanadha

    2015-04-01

    Full Text Available In the present study, an attempt has been made to evaluate starch acetate in combination with surfactant for the controlled release profile of drug from matrix system. Ibuprofen was used as a model drug to evaluate its release characteristics from different matrices. Starch acetate was synthesized, characterized and then employed in the matrix tablets as a hydrophobic polymer in different ratios in combination with SLS. Formulated tablets were characterized for parameters like thickness, weight variation, drug content uniformity, hardness, friability and in-vitro release rate profile and the release data were analysed as per various kinetic models. From the data it was found that the release was following first order kinetics for all the formulationsexcept F8 release profile of which followed zero order and the mechanism of release was found to be Non-fickian diffusion for all the formulations.

  10. Electrospinning nanofibers for controlled drug release

    Science.gov (United States)

    Banik, Indrani

    Electrospinning is the most widely studied technique for the synthesis of nanofibers. Electrospinning is considered as one of the technologies that can produce nanosized drugs incorporated in polymeric nanofibers. In vitro and in vivo studies have demonstrated that the release rates of drugs from these nanofiber formulations are enhanced compared to those from original drug substance. This technology has the potential for enhancing the oral delivery of poorly soluble drugs. The electrospun mats were made using Polycaprolactone/PCL, Poly(DL-lactide)/PDL 05 and Poly(DL-lactide-co-glycolide)/PLGA. The drugs incorporated in the electrospun fibers were 5-Fluorouracil and Rapamycin. The evidence of the drugs being embedded in the polymers was obtained by scanning electron microscopy (SEM), Raman and infrared spectroscopy. The release of 5-Fluorouracil and Rapamycin were followed by UV-VIS spectroscopy.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. Control-release microcapsule of famotidine loaded biomimetic synthesized mesoporous silica nanoparticles: Controlled release effect and enhanced stomach adhesion in vitro.

    Science.gov (United States)

    Li, Jing; Wang, Hongyu; Yang, Baixue; Xu, Lu; Zheng, Nan; Chen, Hongtao; Li, Sanming

    2016-01-01

    In the present work, control-release microcapsule of famotidine (FMT) loaded biomimetic synthesized mesoporous silica nanoparticles (B-MSNs) was developed, and controlled release effect and stomach adhesion of this formulation in vitro were mainly investigated. B-MSN was previously synthesized and it was amorphous mesoporous nanoparticles with helical channels. Cytotoxicity of B-MSN was studied using human breast cancer cells (MCF-7) and the result indicated that cytotoxicity of B-MSN can be neglected. After loading FMT into B-MSN, specific surface area, pore volume and pore diameter of B-MSN were obviously reduced. In vitro dissolution test showed that B-MSN had the ability to slow down FMT release for 15 min. In order to prolong controlled release effect and remained the advantage of B-MSN (improve drug stability due to its rigid silica framework), the combined application of control-release microcapsule (using cellulose and hydroxypropyl methylcellulose K15M as excipients) with B-MSN was designed. It was obvious that newly designed formulation significantly controlled FMT release with Fickian diffusion mechanism and showed enhanced stomach adhesion in vitro, which has significant value in widening the application of B-MSN in formulation design.

  19. Local control of striatal dopamine release

    Directory of Open Access Journals (Sweden)

    Roger eCachope

    2014-05-01

    Full Text Available The mesolimbic and nigrostriatal dopamine (DA systems play a key role in the physiology of reward seeking, motivation and motor control. Importantly, they are also involved in the pathophysiology of Parkinson’s and Huntington’s disease, schizophrenia and addiction. Control of DA release in the striatum is tightly linked to firing of DA neurons in the ventral tegmental area (VTA and the substantia nigra (SN. However, local influences in the striatum affect release by exerting their action directly on axon terminals. For example, endogenous glutamatergic and cholinergic activity is sufficient to trigger striatal DA release independently of cell body firing. Recent developments involving genetic manipulation, pharmacological selectivity or selective stimulation have allowed for better characterization of these phenomena. Such termino-terminal forms of control of DA release transform considerably our understanding of the mesolimbic and nigrostriatal systems, and have strong implications as potential mechanisms to modify impaired control of DA release in the diseased brain. Here, we review these and related mechanisms and their implications in the physiology of ascending DA systems.

  20. 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

  1. Electrosprayed nanoparticle delivery system for controlled release

    Energy Technology Data Exchange (ETDEWEB)

    Eltayeb, Megdi, E-mail: megdi.eltayeb@sustech.edu [Department of Biomedical Engineering, Sudan University of Science and Technology, PO Box 407, Khartoum (Sudan); Stride, Eleanor, E-mail: eleanor.stride@eng.ox.ac.uk [Institute of Biomedical Engineering, Department of Engineering Science, University of Oxford, Old Road Campus Research Building, Headington OX3 7DQ (United Kingdom); Edirisinghe, Mohan, E-mail: m.edirisinghe@ucl.ac.uk [Department of Mechanical Engineering, University College London, Torrington Place, London WC1E 7JE (United Kingdom); Harker, Anthony, E-mail: a.harker@ucl.ac.uk [London Centre for Nanotechnology, Gordon Street, London WC1H 0AH (United Kingdom); Department of Physics & Astronomy, University College London, Gower Street, London WC1E 6BT (United Kingdom)

    2016-09-01

    This study utilises an electrohydrodynamic technique to prepare core-shell lipid nanoparticles with a tunable size and high active ingredient loading capacity, encapsulation efficiency and controlled release. Using stearic acid and ethylvanillin as model shell and active ingredients respectively, we identify the processing conditions and ratios of lipid:ethylvanillin required to form nanoparticles. Nanoparticles with a mean size ranging from 60 to 70 nm at the rate of 1.37 × 10{sup 9} nanoparticles per minute were prepared with different lipid:ethylvanillin ratios. The polydispersity index was ≈ 21% and the encapsulation efficiency ≈ 70%. It was found that the rate of ethylvanillin release was a function of the nanoparticle size, and lipid:ethylvanillin ratio. The internal structure of the lipid nanoparticles was studied by transmission electron microscopy which confirmed that the ethylvanillin was encapsulated within a stearic acid shell. Fourier transform infrared spectroscopy analysis indicated that the ethylvanillin had not been affected. Extensive analysis of the release of ethylvanillin was performed using several existing models and a new diffusive release model incorporating a tanh function. The results were consistent with a core-shell structure. - Highlights: • Electrohydrodynamic spraying is used to produce lipid-coated nanoparticles. • A new model is proposed for the release rates of active components from nanoparticles. • The technique has potential applications in food science and medicine. • Electrohydrodynamic processing controlled release lipid nanoparticles.

  2. 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.

  3. 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

  4. Formulating entompathogens for control of boring beetles in avocado orchards

    Science.gov (United States)

    A foam formulation of Beauveria bassiana was adapted to control boring beetles in avocado orchards. The two geographically independent avocado growing areas in the United States are threatened by emerging diseases vectored by boring beetles. In the California growing region, Fusarium dieback is vect...

  5. 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...

  6. Evaluation of Sterculia foetida gum as controlled release excipient.

    Science.gov (United States)

    Chivate, Amit Ashok; Poddar, Sushilkumar Sharatchandra; Abdul, Shajahan; Savant, Gaurav

    2008-01-01

    The purpose of the research was to evaluate Sterculia foetida gum as a hydrophilic matrix polymer for controlled release preparation. For evaluation as a matrix polymer; characterization of Sterculia foetida gum was done. Viscosity, pH, scanning electronmicrographs were determined. Different formulation aspects considered were: gum concentration (10-40%), particle size (75-420 microm) and type of fillers and those for dissolution studies; pH, and stirring speed were considered. Tablets prepared with Sterculia foetida gum were compared with tablets prepared with Hydroxymethylcellulose K15M. The release rate profiles were evaluated through different kinetic equations: zero-order, first-order, Higuchi, Hixon-Crowell and Korsemeyer and Peppas models. The scanning electronmicrographs showed that the gum particles were somewhat triangular. The viscosity of 1% solution was found to be 950 centipoise and pH was in range of 4-5. Suitable matrix release profile could be obtained at 40% gum concentration. Higher sustained release profiles were obtained for Sterculia foetida gum particles in size range of 76-125 microm. Notable influences were obtained for type of fillers. Significant differences were also observed with rotational speed and dissolution media pH. The in vitro release profiles indicated that tablets prepared from Sterculia foetida gum had higher retarding capacity than tablets prepared with Hydroxymethylcellulose K15M prepared tablets. The differential scanning calorimetry results indicated that there are no interactions of Sterculia foetida gum with diltiazem hydrochloride. It was observed that release of the drug followed through surface erosion and anomalous diffusion. Thus, it could be concluded that Sterculia foetida gum could be used a controlled release matrix polymer.

  7. 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

  8. 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.

  9. 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

  10. 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.

  11. Poly (lactic-co-glycolic acid) controlled release systems: experimental and modeling insights

    Science.gov (United States)

    Hines, Daniel J.; Kaplan, David L.

    2013-01-01

    Poly-lactic-co-glycolic acid (PLGA) has been the most successful polymeric biomaterial for use in controlled drug delivery systems. There are several different chemical and physical properties of PLGA that impact the release behavior of drugs from PLGA delivery devices. These properties must be considered and optimized in drug release device formulation. Mathematical modeling is a useful tool for identifying, characterizing, and predicting the mechanisms of controlled release. The advantages and limitations of poly (lactic-co-glycolic acid) for controlled release are reviewed, followed by a review of current approaches in controlled release technology that utilize PLGA. Mathematical modeling applied towards controlled release rates from PLGA-based devices will also be discussed to provide a complete picture of state of the art understanding of the control achievable with this polymeric system, as well as the limitations. PMID:23614648

  12. Poly(lactic-co-glycolic) acid-controlled-release systems: experimental and modeling insights.

    Science.gov (United States)

    Hines, Daniel J; Kaplan, David L

    2013-01-01

    Poly(lactic-co-glycolic acid) (PLGA) has been the most successful polymeric biomaterial used in controlled drug delivery systems. There are several different chemical and physical properties of PLGA that impact the release behavior of drugs from PLGA delivery devices. These properties must be considered and optimized in the formulation of drug release devices. Mathematical modeling is a useful tool for identifying, characterizing, and predicting mechanisms of controlled release. The advantages and limitations of poly(lactic-co-glycolic acid) for controlled release are reviewed, followed by a review of current approaches in controlled-release technology that utilize PLGA. Mathematical modeling applied toward controlled-release rates from PLGA-based devices also will be discussed to provide a complete picture of a state-of-the-art understanding of the control that can be achieved with this polymeric system, as well as the limitations.

  13. 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.

  14. 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.

  15. Quality control of an antipsoriatic ayurvedic herbal Formulation: Lajjalu Keram

    Directory of Open Access Journals (Sweden)

    M T Athar

    2016-01-01

    Full Text Available Background: Psoriasis is an autoimmune disorder, which affects a large group of human population of world (3%. Till date, there is no treatment for psoriasis except some herbal drugs and its constituents. Since Ayurveda is the main traditional system of medicine in India, here, we have selected one ayurvedic formulation - Lajjalu Keram, which has been used since long for their quality control. Methods: Total microbial load of formulations were carried out for total fungal count and total bacterial count. Lajjalu Keram was also tested by high-performance liquid chromatographic (HPLC for aflatoxins (B1, B2, G1, and G2, which showed its presence below the permissible limit; similarly, pesticides residues were analyzed using gas chromatography/mass spectrometry for organophosphates and organochlorides, which showed that pesticides were below detection limit (0.1 ppb. The content of heavy metals was analyzed using AAS, which demonstrated the presence of cadmium, lead, and arsenic below permissible limit, whereas mercury was found absent. Results: The result of quality control analysis showed the presence of alkaloids, tannins, carbohydrate, saponins, proteins and amino acids, lipid/fats, phenolic compounds, and flavonoids in formulation. The dermal toxicity (LD50 of Lajjalu Keram in Wistar rats was found more than 2000 mg/kg (safe for the management of psoriasis. Formulation was also analyzed for their composition of fatty acids. It was found to have 13 fatty acids, out of which, seven were saturated fatty acids (95.2% and the rest were unsaturated fatty acids (3.27%. A rapid HPLC method for quantification of mimosine (an unusual amino acid present in formulation has been developed and validated. The mimosine content in Lajjalu Keram was found to be 0.0070% w/w with % relative standard deviation of 0.41. Conclusion: The formulation afforded significant and better protection of carrageenan-induced rat paw edema (72.11% inhibition as compared to

  16. 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.

  17. Controlled-release of Avermectin from Organically Modified Hydrotalcite-like Compound Nanohybrids

    Institute of Scientific and Technical Information of China (English)

    QIU,Depeng; LI,Yonghai; FU,Xiying; JIANG,Zhen; ZHAO,Xinyan; WANG,Tian; HOU,Wanguo

    2009-01-01

    The intercalation of avermectin (AVM)into sodium dodecyl sulfate(SDS)modified hydrotalcite-like com-pounds(HTlc) was carried out using an evaporating solvent enhanced intercalation method to obtain AVM-SDS-HTlc nanohybrids. It was found that the nanohybrids could well control the release of avermectin, showing the nanohybrids are a potential pesticide controlled-release formulation.The release of avermectin from AVM-SDS-HTlc nanohybrids is dependent on the pH.temperature and the presence of electrolyte in release me-dium. Acidic medium and higher temperature and the presence of electrolytes may induce the higher release rate of avermectin. The release process of avermectin from AVM-SDS-HTlc nanohybrids can be described by pseudo-first-order release kinetics, and the activation energy of release is 279 kJ/mol.

  18. Controlled-Release Personal Use Arthropod Repellent Formulation. Phase 2

    Science.gov (United States)

    1986-09-15

    group but none in the washed group. Conjunctival blanching and corneal epithelial peeling in all unwashed and one washed animal. Petite...Conjunctival blanching in all eyes. Corneal epithelial peeling in unwashed eyes and in two of three washed eyes. Five of six unwashed eyes had all zero...prevent the carryover of any negative opinion of the latter. This tube will easily fit into the blouse pocket of a battledress uniform. Initial

  19. 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.

  20. Studies on pectins as potential hydrogel matrices for controlled-release drug delivery.

    Science.gov (United States)

    Sungthongjeen, S; Pitaksuteepong, T; Somsiri, A; Sriamornsak, P

    1999-12-01

    Polymeric hydrogels are widely used as controlled-release matrix tablets. In the present study, we investigated high-methoxy pectins for their potential value in controlled-release matrix formulations. The effects of compression force, ratio of drug to pectin, and type of pectin on drug release from matrix tablets were also investigated. The results of the in vitro release studies show that the drug release from compressed matrix tablets prepared from pectin can be modified by changing the amount and the type of pectin in the matrix tablets. However, compression force did not significantly affect the drug release. The mechanisms controlling release rate were discussed with respect to drug diffusion through the polymer matrices, but may be more complex.

  1. Preventing and controlling accidental gas releases

    Science.gov (United States)

    Moskowitz, P. D.; Fthenakis, V. M.; Kalb, P. D.

    1988-07-01

    Toxic, flammable, and explosive gases may be used in photovoltaic cell research laboratories and in commercial manufacturing facilities. Accidental release of these materials can present hazards to life and property. Accidents can arise from a variety of mechanical and human related failures. These can occur from the time materials are received at the loading dock of the facility to the time treated gases are discharged to the atmosphere through a stack. Each type of initiating event may require a different control approach. These may range from the training and certification of plant workers charged with the handling of gas cylinder hookups to installation of emergency pollution control systems. Since engineering options for controlling released materials are limited, emphasis should be placed on administrative and engineering approaches for preventing such accidents. These are likely to be the most effective approaches for protecting life and property.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  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. 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 ...

  8. 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.

  9. Controlled release fertilizer workshop, 1991: Proceedings

    Energy Technology Data Exchange (ETDEWEB)

    Scheib, R.M. [ed.

    1991-11-01

    Over the last 20 years the Tennessee Valley Authority`s National Fertilizer and Environmental Research Center (NFERC) has carried out a number of programs to develop controlled release fertilizers. They pioneered the development and commercialization of sulfur coated urea and conducted extensive research in an attempt to develop an economical synthesis for oxamide. In recent years there has developed an increasing interest in the environmental impact of fertilizers, particularly on the potential for ground water contamination by nitrate derived from fertilizer materials. In response to this interest NFERC`s Chemical Research Department organized a five member Controlled Release Fertilizer (CRF) Team to reassess the potential for controlled release materials in agriculture with a view to minimizing any adverse environmental impact and increasing the efficiency of nutrient utilization by the crop. This workshop was part of that reassessment program. The workshop goals were: To determine the present status of CRF research, production and use; to assess the future needs of CRF producers and consumers; and to promote communication and exchange of information. To accomplish these goals the team invited speakers from across` the United States representing academics, experimental station researchers, fertilizer producers, environmentalists, and marketing experts to present papers.

  10. Controlled release fertilizer workshop, 1991: Proceedings

    Energy Technology Data Exchange (ETDEWEB)

    Scheib, R.M. (ed.)

    1991-11-01

    Over the last 20 years the Tennessee Valley Authority's National Fertilizer and Environmental Research Center (NFERC) has carried out a number of programs to develop controlled release fertilizers. They pioneered the development and commercialization of sulfur coated urea and conducted extensive research in an attempt to develop an economical synthesis for oxamide. In recent years there has developed an increasing interest in the environmental impact of fertilizers, particularly on the potential for ground water contamination by nitrate derived from fertilizer materials. In response to this interest NFERC's Chemical Research Department organized a five member Controlled Release Fertilizer (CRF) Team to reassess the potential for controlled release materials in agriculture with a view to minimizing any adverse environmental impact and increasing the efficiency of nutrient utilization by the crop. This workshop was part of that reassessment program. The workshop goals were: To determine the present status of CRF research, production and use; to assess the future needs of CRF producers and consumers; and to promote communication and exchange of information. To accomplish these goals the team invited speakers from across' the United States representing academics, experimental station researchers, fertilizer producers, environmentalists, and marketing experts to present papers.

  11. 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.

  12. 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.

  13. Formulation and evaluation of starch acetate matrix tablets in combination with surfactants for controlled release”

    OpenAIRE

    Mahesh Kumar Vishwanadha; B. Shravan Kumar; Rajasri. Ch; Mounika.G; Ramya.D; Saikrupa.B

    2015-01-01

    In the present study, an attempt has been made to evaluate starch acetate in combination with surfactant for the controlled release profile of drug from matrix system. Ibuprofen was used as a model drug to evaluate its release characteristics from different matrices. Starch acetate was synthesized, characterized and then employed in the matrix tablets as a hydrophobic polymer in different ratios in combination with SLS. Formulated tablets were characterized for parameters like thickness, weig...

  14. A mathematical formulation for optimal control of air pollution

    Institute of Scientific and Technical Information of China (English)

    朱江; 曾庆存

    2003-01-01

    The problem of optimal control of air pollution using weather forecastresults and numerical air pollution models is discussed. A mathematical formulation of the problem is presented. The control is an act on pollution sources with feasible constraints. Based on forecasted weather conditions, the objective ofthe optimal control is to minimize total cost caused by control under the constraint that the pollution concentrations over a certain period and a certain spatial domain are less than some specified values. Using the adjoint method, an effective algorithm is given. Since the optimal solutions are based on weather forecasts, the errors in weather forecasts will cause uncertainties in the optimal solutions. Estimation of impacts of weather forecast errors on the optimal solutions is discussed using the adjoint sensitivity analysis technique that is an approximated, however very effective method. The adjoint sensitivity analysis technique can be used to calculate the impacts of errors in wind, temperature and initial pollutant concentration fields on performances of the optimal control.

  15. 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.

  16. 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.

  17. 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.

  18. Designer protein delivery: From natural to engineered affinity-controlled release systems.

    Science.gov (United States)

    Pakulska, Malgosia M; Miersch, Shane; Shoichet, Molly S

    2016-03-18

    Exploiting binding affinities between molecules is an established practice in many fields, including biochemical separations, diagnostics, and drug development; however, using these affinities to control biomolecule release is a more recent strategy. Affinity-controlled release takes advantage of the reversible nature of noncovalent interactions between a therapeutic protein and a binding partner to slow the diffusive release of the protein from a vehicle. This process, in contrast to degradation-controlled sustained-release formulations such as poly(lactic-co-glycolic acid) microspheres, is controlled through the strength of the binding interaction, the binding kinetics, and the concentration of binding partners. In the context of affinity-controlled release--and specifically the discovery or design of binding partners--we review advances in in vitro selection and directed evolution of proteins, peptides, and oligonucleotides (aptamers), aided by computational design.

  19. 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.

  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. 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.

  2. 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.

  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. Controlled release fungicide, soil amendments and biofumigation effects on cotton root rot suppression

    Science.gov (United States)

    The cotton root rot pathogen (Phymatotrichopsis ominora) causes major losses in cotton produced in the Southwest. Granular controlled release formulations (CRF) of the fungicide, Propiconazole, developed to be soil applied at planting were studied at 1.0 and 3.0 lb a.i./ac. applications and with tw...

  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. A Responsive Battery with Controlled Energy Release.

    Science.gov (United States)

    Wang, Xiaopeng; Gao, Jian; Cheng, Zhihua; Chen, Nan; Qu, Liangti

    2016-11-14

    A new type of responsive battery with the fascinating feature of pressure perceptibility has been developed, which can spontaneously, timely and reliably control the power outputs (e.g., current and voltage) in response to pressure changes. The device design is based on the structure of the Zn-air battery, in which graphene-coated sponge serves as pressure-sensitive air cathode that endows the whole system with the capability of self-controlled energy release. The responsive batteries exhibit superior battery performance with high open-circuit voltage (1.3 V), and competitive areal capacity of 1.25 mAh cm(-2) . This work presents an important move towards next-generation intelligent energy storage devices with energy management function. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Bilayer Tablet Formulation of Metformin HCl and Acarbose: A Novel Approach To Control Diabetes.

    Science.gov (United States)

    Tiwari, Ruchi; Gupta, Ankita; Joshi, Meenakshi; Tiwari, Gaurav

    2014-01-01

    The present investigation studied a novel bilayer tablet having an extended release system of metformin HCl with Eudragit RS 100 and RL 100 and an immediate release system of acarbose with polyvinylpyrrolidone K30 (PVP K30) and polyethylene glycol 6000 (PEG 6000) in different ratios using solvent evaporation and cogrinding techniques. Solid dispersions (SDs) were characterized by Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), powder x-ray diffractometry (XRD), scanning electron microscopy (SEM), as well as by content uniformity, in vitro dissolution studies, and release kinetics. The selected SD system was subjected to bilayer tablet preparation by direct compression. Compressed tablets were evaluated for drug content, weight variation, friability, hardness, and thickness, and they underwent in vitro dissolution studies. The progressive disappearance of IR, x-ray, and thermotropic drug signals in SDs and physical mixtures were related to increasing amount of polymer. SEM studies suggested the homogenous dispersion of drug in polymers. FT-IR studies confirmed the formation of hydrogen bonding between drug and polymer. All tablet formulations showed compliance with pharmacopoeial standards. The formulations gave an initial burst effect to provide the loading dose of the drug followed by extended release for 12 h (Higuchi model via a non-Fickian diffusion controlled release mechanism). Stability studies conducted for the optimized formulation did not show any change in physical properties, drug content, or in vitro drug release. The goal of diabetes therapy today is to achieve and maintain as near normal glycemia as possible to prevent the long-term microvascular and macrovascular complications of elevated blood glucose levels. Oral therapeutic options for the treatment of type 2 diabetes mellitus, until recently, have been severely limited. Metformin, a biguanide, targets additional mechanisms of hyperglycemia by inhibiting

  11. 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.

  12. Use of hydrophilic and hydrophobic polymers for the development of controlled release tizanidine matrix tablets

    Directory of Open Access Journals (Sweden)

    Tariq Ali

    2014-12-01

    Full Text Available The aim of the present study was to develop tizanidine controlled release matrix. Formulations were designed using central composite method with the help of design expert version 7.0 software. Avicel pH 101 in the range of 14-50% was used as a filler, while HPMC K4M and K100M in the range of 25-55%, Ethylcellulose 10 ST and 10FP in the range of 15 - 45% and Kollidon SR in the range of 25-60% were used as controlled release agents in designing different formulations. Various physical parameters including powder flow for blends and weight variation, thickness, hardness, friability, disintegration time and in-vitro release were tested for tablets. Assay of tablets were also performed as specified in USP 35 NF 32. Physical parameters of both powder blend and compressed tablets such as compressibility index, angle of repose, weight variation, thickness, hardness, friability, disintegration time and assay were evaluated and found to be satisfactory for formulations K4M2, K4M3, K4M9, K100M2, K100M3, K100M9, E10FP2, E10FP9, KSR2, KSR3 & KSR9. In vitro dissolution study was conducted in 900 ml of 0.1N HCl, phosphate buffer pH 4.5 and 6.8 medium using USP Apparatus II. In vitro release profiles indicated that formulations prepared with Ethocel 10 standard were unable to control the release of drug while formulations K4M2, K100M9, E10FP2 & KSR2 having polymer content ranging from 40-55% showed a controlled drug release pattern in the above mentioned medium. Zero-order drug release kinetics was observed for formulations K4M2, K100M9, E10FP2 & KSR2. Similarity test (f2 results for K4M2, E10FP2 & KSR2 were found to be comparable with reference formulation K100M9. Response Surface plots were also prepared for evaluating the effect of independent variable on the responses. Stability study was performed as per ICH guidelines and the calculated shelf life was 24-30 months for formulation K4M2, K100M9 and E10FP2.

  13. 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.

  14. 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...

  15. 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.

  16. Gelatin methacrylate microspheres for controlled growth factor release.

    Science.gov (United States)

    Nguyen, Anh H; McKinney, Jay; Miller, Tobias; Bongiorno, Tom; McDevitt, Todd C

    2015-02-01

    Gelatin has been commonly used as a delivery vehicle for various biomolecules for tissue engineering and regenerative medicine applications due to its simple fabrication methods, inherent electrostatic binding properties, and proteolytic degradability. Compared to traditional chemical cross-linking methods, such as the use of glutaraldehyde (GA), methacrylate modification of gelatin offers an alternative method to better control the extent of hydrogel cross-linking. Here we examined the physical properties and growth factor delivery of gelatin methacrylate (GMA) microparticles (MPs) formulated with a wide range of different cross-linking densities (15-90%). Less methacrylated MPs had decreased elastic moduli and larger mesh sizes compared to GA MPs, with increasing methacrylation correlating to greater moduli and smaller mesh sizes. As expected, an inverse correlation between microparticle cross-linking density and degradation was observed, with the lowest cross-linked GMA MPs degrading at the fastest rate, comparable to GA MPs. Interestingly, GMA MPs at lower cross-linking densities could be loaded with up to a 10-fold higher relative amount of growth factor than conventional GA cross-linked MPs, despite the GA MPs having an order of magnitude greater gelatin content. Moreover, a reduced GMA cross-linking density resulted in more complete release of bone morphogenic protein 4 and basic fibroblast growth factor and accelerated release rate with collagenase treatment. These studies demonstrate that GMA MPs provide a more flexible platform for growth factor delivery by enhancing the relative binding capacity and permitting proteolytic degradation tunability, thereby offering a more potent controlled release system for growth factor delivery.

  17. Control of noradrenaline release from hippocampal synaptosomes

    Energy Technology Data Exchange (ETDEWEB)

    West, D.P.; Fillenz, M.

    1981-10-01

    Potassium-evoked tritiated noradrenaline (NA) release from hippocampal synaptosomes was measured with a superfusion method. A single 2-min high-K+ pulse released 39% of the vesicular NA by a Ca2+-dependent mechanism: the Ca2+-independent release was negligible. After changing the vesicular NA store size by pretreating rats with either alpha-methyl-para-tyrosine, 500 mg/kg, or tranylcypromine, 10 mg/kg, a single K+ pulse released a constant percentage of the vesicular NA. With two K+ pulses, however, there was a reduction in the percentage of vesicular NA released in response to the second pulse.

  18. 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.

  19. Formulation to Enhance the Insecticidal Activity of Entomopathogenic Nematodes for Control of Insect Pests of Orchards

    Science.gov (United States)

    Extended shelf life and rapid dispersion of entomopathogenic nematode (EPN) infective juveniles (IJs) in spray suspensions were the principal objectives of earlier EPN formulation development. Subsequently, formulation of EPNs for enhanced insecticidal control in greenhouses and field has been inves...

  20. Biological control of weeds release sites : Kulm Wetland Management District

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — Table of release sites of insects for biological control of invasive plants at Kulm Wetland Management District (WMD). Insects were released on Kulm WMD to...

  1. Release mechanisms behind polysaccharides-based famotidine controlled release matrix tablets.

    Science.gov (United States)

    Elmowafy, Enas M; Awad, Gehanne A S; Mansour, Samar; El-Shamy, Abd El-Hamid A

    2008-01-01

    Polysaccharides, which have been explored to possess gelling properties and a wide margin of safety, were used to formulate single-unit floating matrix tablets by a direct compression technique. This work has the aim to allow continuous slow release of famotidine above its site of absorption. The floating approach was achieved by the use of the low density polypropylene foam powder. Polysaccharides (kappa-carrageenan, gellan gum, xyloglucan, and pectin) and blends of polysaccharides (kappa-carrageenan and gellan gum) and cellulose ethers (hydroxypropylmethyl cellulose, hydroxypropylcellulose, sodium carboxymethyl cellulose) were tried to modulate the release characteristics. The prepared floating tablets were evaluated for their floating behavior, matrix integrity, swelling studies, in vitro drug release studies, and kinetic analysis of the release data. The differential scanning calorimetry and Fourier transform infrared spectroscopy studies revealed that changing the polymer matrix system by formulation of polymers blends resulted in formation of molecular interactions which may have implications on drug release characteristics. This was obvious from the retardation in drug release and change in its mechanistics.

  2. A Controlled Antibiotic Release System for the Development of Single-Application Otitis Externa Therapeutics

    Directory of Open Access Journals (Sweden)

    Bogdan A. Serban

    2017-05-01

    Full Text Available Ear infections are a commonly-occurring problem that can affect people of all ages. Treatment of these pathologies usually includes the administration of topical or systemic antibiotics, depending on the location of the infection. In this context, we sought to address the feasibility of a single-application slow-releasing therapeutic formulation of an antibiotic for the treatment of otitis externa. Thixotropic hydrogels, which are gels under static conditions but liquefy when shaken, were tested for their ability to act as drug controlled release systems and inhibit Pseudomonas aeruginosa and Staphylococcus aureus, the predominant bacterial strains associated with outer ear infections. Our overall proof of concept, including in vitro evaluations reflective of therapeutic ease of administration, formulation stability, cytocompatibility assessment, antibacterial efficacy, and formulation lifespan, indicate that these thixotropic materials have strong potential for development as otic treatment products.

  3. Controlled delivery of paclitaxel from stent coatings using novel styrene maleic anhydride copolymer formulations.

    Science.gov (United States)

    Richard, Robert; Schwarz, Marlene; Chan, Ken; Teigen, Nikolai; Boden, Mark

    2009-08-01

    The controlled release of paclitaxel (PTx) from stent coatings comprising an elastomeric polymer blended with a styrene maleic anhydride (SMA) copolymer is described. The coated stents were characterized for morphology by scanning electron microscopy (SEM) and atomic force microscopy (AFM), and for drug release using high-performance liquid chromatography (HPLC). Differential scanning calorimetry (DSC) was used to measure the extent of interaction between the PTx and polymers in the formulation. Coronary stents were coated with blends of poly(b-styrene-b-isobutylene-b-styrene) (SIBS) and SMA containing 7% or 14% maleic anhydride (MA) by weight. SEM examination of the stents showed that the coating did not crack or delaminate either before or after stent expansion. Examination of the coating surface via AFM after elution of the drug indicated that PTx resides primarily in the SMA phase and provided information about the mechanism of PTx release. The addition of SMA altered the release profile of PTx from the base elastomer coatings. In addition, the presence of the SMA enabled tunable release of PTx from the elastomeric stent coatings, while preserving mechanical properties. Thermal analysis reveled no shift in the glass transition temperatures for any of the polymers at all drug loadings studied, indicating that the PTx is not miscible with any component of the polymer blend. An in vivo evaluation indicated that biocompatibility and vascular response results for SMA/SIBS-coated stents (without PTx) are similar to results for SIBS-only-coated and bare stainless steel control stents when implanted in the non-injured coronary arteries of common swine for 30 and 90 days.

  4. Desktop 3D printing of controlled release pharmaceutical bilayer tablets.

    Science.gov (United States)

    Khaled, Shaban A; Burley, Jonathan C; Alexander, Morgan R; Roberts, Clive J

    2014-01-30

    Three dimensional (3D) printing was used as a novel medicine formulation technique for production of viable tablets capable of satisfying regulatory tests and matching the release of standard commercial tablets. Hydroxypropyl methylcellulose (HPMC 2208) (Methocel™ K100M Premium) and poly(acrylic acid) (PAA) (Carbopol(®) 974P NF) were used as a hydrophilic matrix for a sustained release (SR) layer. Hypromellose(®) (HPMC 2910) was used as a binder while microcrystalline cellulose (MCC) (Pharmacel(®) 102) and sodium starch glycolate (SSG) (Primojel(®)) were used as disintegrants for an immediate release (IR) layer. Commercial guaifenesin bi-layer tablets (GBT) were used as a model drug (Mucinex(®)) for this study. There was a favourable comparison of release of the active guaifenesin from the printed hydrophilic matrix compared with the commercially available GBT. The printed formulations were also evaluated for physical and mechanical properties such as weight variation, friability, hardness and thickness as a comparison to the commercial tablet and were within acceptable range as defined by the international standards stated in the United States Pharmacopoeia (USP). All formulations (standard tablets and 3D printed tablets) showed Korsmeyer-Peppas n values between 0.27 and 0.44 which indicates Fickian diffusion drug release through a hydrated HPMC gel layer. Copyright © 2013 Elsevier B.V. All rights reserved.

  5. 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).

  6. Evaluation of Calendula mucilage as a mucoadhesive and controlled release component in buccal tablets.

    Science.gov (United States)

    Sabale, V; Patel, V; Paranjape, A

    2014-01-01

    Mucoadhesive drug delivery systems were developed to sustain drug delivery via various mucus membranes for either local or systemic delivery of poorly absorbed drugs such as peptides and proteins as well as drugs that are subjected to high first-pass metabolism. The present study was undertaken to use isolated Calendula mucilage as a mucoadhesive agent and to formulate controlled release buccoadhesive tablets with an intention to avoid hepatic first-pass metabolism as well as to enhance residence time of drug in the buccal cavity. The mucilage was isolated from the Calendula petals by aqueous extraction method and characterized for various physiochemical parameters as well as for its adhesive properties. By using direct compression technique, tablets were prepared containing dried mucilage and chlorpheniramine maleate (CPM) as a model drug. Three batches of tablets were prepared and evaluated containing three mucoadhesive components namely Methocel K4M, Carbopol 974P and isolated Calendula mucilage in 16.66%, 33.33 % and 50 % (1:2:3 ratio) resulting in 9 different formulations. FTIR studies between mucilage and CPM suggested the absence of a chemical interaction between CPM and Calendula mucilage. The results of the study showed that the isolated mucilage had good physicochemical and morphological characteristics and tablets conformed to the pharmacopoeial specifications. Also in vitro release studies showed controlled action of drug with increasing the concentration of the isolated Calendula mucilage as a mucoadhesive agent in the formulations. Permeability studies indicated that permeability behavior was not statistically different (P>0.05) by changing the mucoadhesive component. The formulated mucoadhesive tablets for buccal administration containing 75 mg Calendula mucilage showed controlled drug release. Thus, mucoadhesive natural Calendula mucilage based buccal tablets for controlled release were successfully formulated.

  7. 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.

  8. 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.

  9. Sustained-release morphine sulfate with sequestered naltrexone for moderate to severe pain: a new opioid analgesic formulation and beyond.

    Science.gov (United States)

    Ruan, Xiulu

    2011-05-01

    Opioid usage during chronic nonmalignant pain has increased substantially over the past two decades. Prescription opioids have become the second most misused drug in the USA and prescription opioid abuse has escalated into a widespread public health problem. It is hoped that abuse-deterrent opioid formulations will take an important role in reducing opioid abuse, misuse and diversion. Embeda (sustained-release morphine sulfate with sequestered naltrexone)represents a new opioid formulation with an intended abuse-deterrent feature, now available on the market. Although Embeda seems to be a successful formulation by passing the efficacy trial, safety trial, pharmacokinetic study and abuse liability study, etc., it will require some long-term prospective epidemiological studies to substantiate fully its abuse-deterrent benefit. Embeda represents a new opioid formulation, adding to our arsenal to treat moderate to severe pain and playing its potential role in discouraging opioid abuse, misuse and diversion. Faced with an overwhelmingly expanding public health burden due to prescription opioid abuse, clinicians should always keep in mind the balance of maximizing pain relief and minimizing prescription opioid abuse.

  10. 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

  11. 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.

  12. 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.

  13. Molecularly imprinted nanotubes for enantioselective drug delivery and controlled release.

    Science.gov (United States)

    Yin, Junfa; Cui, Yue; Yang, Gengliang; Wang, Hailin

    2010-11-07

    Molecularly imprinted nanotubes for enantioselective drug delivery and controlled release are fabricated by the combination of template synthesis and ATRP grafting. The release of R-propranolol from the imprinted nanotubes in rats is restricted while the release of pharmacologically active S-enantiomer is greatly promoted.

  14. Analytical solution of diffusion model for nutrient release from controlled release fertilizer

    Science.gov (United States)

    Ameenuddin Irfan, Sayed; Razali, Radzuan; KuShaari, KuZilati; Mansor, Nurlidia; Azeem, Babar

    2017-09-01

    An analytical method has been developed to solve the initial value problem which arises from Fick’s diffusion equation encountered in the modelling of the Controlled Release Fertilizers. The proposed analytical solution is developed using the modified Adomian decomposition method. This method does not require the discretization method, reliability and efficiency of this method is more and it also reduces the calculation time. The model has predicted the effect of granule radius and diffusion coefficient on the nutrient release and total release time of Controlled Release Fertilizer. Model has predicted that increase in the radius of granule reduces the release and vice versa in case of diffusion coefficient. Detailed understanding of these parameters helps in improved designing of Controlled Release Fertilizer.

  15. Design and in vitro evaluation of controlled release alginate beads of diltiazem hydrochloride

    Institute of Scientific and Technical Information of China (English)

    D.Nagasamy Venkatesh; A.Kalaivani; Kritika D.Kalro; Lalitha Chintha; James Tharani; M.K. Samanta; B.Suresh

    2009-01-01

    Objective:Oral slow and sustained release drug delivery system can release their drug content with a controlled manner,producing a desirable blood serum level,reduction in drug toxicity and improving the patient compli-ance by prolonging dosing intervals.The major drawback of orally administered drug like diltiazem as a calcium channel blocker for the treatment of angina pectoris,arrhythmia and hypertension.Its has higher aqueous solu-bility and shorter elimination half-life.Methods:To overcome these drawbacks associated with diltiazem,an attempt has been made to develop a sustained release dosage form of diltiazem embedded alginate microbeads by ionotropic gelation technique employing various concentrations of polymer and keeping the drug concentra-tion constant.Results:The beads were characterized for its particle size,drug content and in vitro release stud-ies.The results revealed that the surface adhering drug was found to release immediately and a steady state of release was obtained up to 12 h from all the batches.The results indicated there was an inverse relationship be-tween the concentration of alginate and drug release.The drug release was found to follow non-fickian diffusion obeying first order kinetics.Conclusion:The developed alginate microbeads offered a sustained release of dilti-azem.Hence,the formulated microbeads were found to be potential,cost effective,possess satisfactory in vitro release studies.

  16. 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.

  17. 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.

  18. FABRICATION AND EVALUATION OF GLIPIZIDE ABELMOSCHUS ESCULENTUS FRUIT MUCILAGE POVIDONE CONTROLLED RELEASE MATRIX TABLETS

    Directory of Open Access Journals (Sweden)

    Hindustan Abdul Ahad

    2011-02-01

    Full Text Available The present investigation was aimed to prepare matrix type controlled release tablets of Glipizide with Abelmoschus esculentus fruit mucilage and Povidone. The polymers were studied for its functionality as a matrix forming property to sustain the Glipizide release from the dosage form. Physicochemical properties of dried powdered mucilage of Abelmoschus esculentus fruit mucilage and Povidone blend were studied. Various formulations of Glipizide Abelmoschus esculentus fruit mucilage and Povidone were prepared. The prepared tablets were found to have better pharmacopoeial parameters with low standard deviation values. The swelling behavior and release rate characteristics were studied. The in-vitro dissolution study proved that the dried Abelmoschus esculentus fruit mucilage and Povidone in combination can be used as a matrix forming polymers for making controlled release matrix tablets.

  19. The Preparation of Salbutamol Sulfate Controlled Release TabletsCoated with Cellulose Acetate Aqueous Dispersion

    Institute of Scientific and Technical Information of China (English)

    ZhangFengyu; WuTao; PanWeisan; ChenJimin; ZhangRuhua

    2001-01-01

    In this study, emulsion-solvent evaporation method was applied to prepare the cellulose acetate(CA) aqueous dispersion. Upon the analyzing of the character of the aqueous dispersion, a controlled releaseformulation of salbutamol sulfate coated with cellulose acetate aqueous dispersion was prepared through orthogonalexperiment design. The factors that control the drug release character of the tablets were investigated. The drugrelease mechanism of the formulation was also studied. The experimental results indicated that CA aqueousdispersion had excellent film-forming ability under the effect of plasticizer. The drug release profile of the controlledrelease tablets coated with CA aqueous dispersion exhibited zero-order release character and the drug release rate wasmodulated by the osmotic pressure of the dissolution medium.

  20. Effect of diluents on tablet integrity and controlled drug release.

    Science.gov (United States)

    Zhang, Y E; Schwartz, J B

    2000-07-01

    The objective of this study was to evaluate the effect of diluents and wax level on tablet integrity during heat treatment and dissolution for sustained-release formulations and the resultant effect on drug release. Dibasic calcium phosphate dihydrate (DCPD), microcrystalline cellulose (MCC), and lactose were evaluated for their effect on tablet integrity during drug dissolution and heat treatment in wax matrix formulations. A newly developed direct compression diluent, dibasic calcium phosphate anhydrous (DCPA), was also evaluated. Compritol 888 ATO was used as the wax matrix material, with phenylpropanolamine hydrochloride (PPA) as a model drug. Tablets were made by direct compression and then subjected to heat treatment at 80 degrees C for 30 min. The results showed that MCC, lactose, and DCPA could maintain tablets intact during heat treatment above the melting point of wax (70 degrees C-75 degrees C). However, DCPD tablets showed wax egress during the treatment. MCC tablets swelled and cracked during drug dissolution and resulted in quick release. DCPD and lactose tablets remained intact during dissolution and gave slower release than MCC tablets. DCPA tablets without heat treatment disintegrated very quickly and showed immediate release. In contrast, heat-treated DCPA tablets remained intact through the 24-hr dissolution test and only released about 80% PPA at 6 hr. In the investigation of wax level, DCPD was used as the diluent. The drug release rate decreased as the wax content increased from 15% to 81.25%. The dissolution data were best described by the Higuchi square-root-of-time model. Diluents showed various effects during heat treatment and drug dissolution. The integrity of the tablets was related to the drug release rate. Heat treatment retarded drug release if there was no wax egress.

  1. 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...

  2. 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...

  3. Effect of ethylcellulose and propylene glycol on the controlled-release performance of glyceryl monooleate-mertronidazole periodontal gel.

    Science.gov (United States)

    Sallam, Al-Sayed; Hamudi, Firas Falih; Khalil, Enam Ayoub

    2015-03-01

    Controlled-release metronidazole, mucoadhesive gel proposed as a drug-delivery system for periodontal application was developed and characterized. The system was based on a mixture of glycerylmonooleate (GMO) and ethylcellulose (EC). The mechanism of release depends: firstly, on the ability of GMO to form a viscous liquid crystalline mesophases and secondly on the solubilized EC to form a hydrophobic network when the mixture comes into contact with water resulting in sustaining the release of the drug. Ethylcellulose dissolved in GMO had a profound influence on the rate of drug release, reduced the initial drug release and prolonged the sustained release of metronidazole. Propylene glycol (PG) was added to increase the solubility of the drug and water was added with PG to control the viscosity. A controlled release formulation containing w/w, 20% metronidazole, 10% PG, 5% water and 65% GMO that contains 7% EC was found to be mucoadhesive, easily injectable at room temperature, and to follow Fickian diffusion release mechanism. When the drug loading was increased the drug release was accelerated, and the mechanism followed anomalous controlled-release mechanism. Stability studies indicated that the formulation should be stored at 4 °C in a dark place.

  4. 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.

  5. 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.

  6. 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.

  7. [Nutrient release characteristics and use efficiency of slow- and controlled release fertilizers].

    Science.gov (United States)

    Duan, Lu-Lu; Zhang, Min; Liu, Gang; Shang, Zhao-Cong; Yang, Yi

    2009-05-01

    Water extraction method and soil incubation method were used to study the nutrient release characteristics of four slow- and controlled release fertilizers (CRF1, CRF2, SCU, and IBDU), and pot experiment was conducted to assess the effects of the release characteristics on the nutrient requirements of canola (Brassica napus L.). The nutrient release curves of test fertilizers in water were S pattern for CRF1 and CRF2, burst pattern for SCU, and reverse L pattern for IBDU. The nutrient release characteristics of the four fertilizers in water and in soil all fitted binomial equations, suggesting that there existed some similarities in the nutrient release in the two media. The nutrient uptake and biomass of canola plants treated with CRF1 and CRF2 were significantly higher than those treated with SCU and IBDU, and CRF2 had the greatest effect. The nutrient release curves of CRF1 and CRF2 accorded more closely with the nutrient requirements of canola.

  8. Ciprofloxacin Controlled-Solid Lipid Nanoparticles: Characterization, In Vitro Release, and Antibacterial Activity Assessment

    Science.gov (United States)

    2017-01-01

    The objective of this research was to formulate ciprofloxacin (CIP) in solid lipid nanoparticles (SLNs) in an attempt to develop a controlled drug delivery system. An ultrasonic melt-emulsification method was used for preparing CIP-loaded SLNs. Key findings included that SLNs were successfully produced with average particle sizes ranging from 165 to 320 nm and polydispersity index in the range of 0.18–0.33. High entrapment efficiency values were reported in all formulations. The atomic force scanning microscopic images showed spherical shape with the size range closer to those found by the particle size analyzer. CIP release exhibited controlled-release behavior with various lipids. Ciprofloxacin solid lipid nanoparticles formula containing stearic acid (CIPSTE) displayed the strongest burst effect and the most rapid release rate. The release data revealed a better fit to the Higuchi diffusion model. After storing the CIPSTE formula at room temperature for 120 days, no significant difference in particle size and zeta potential was found. CIP-loaded SLNs exhibited superior antibacterial activity. Incorporation of CIP into SLNs leads to controlled release and a superior antibacterial effect of CIP. PMID:28194408

  9. Ciprofloxacin Controlled-Solid Lipid Nanoparticles: Characterization, In Vitro Release, and Antibacterial Activity Assessment

    Directory of Open Access Journals (Sweden)

    Gamal A. Shazly

    2017-01-01

    Full Text Available The objective of this research was to formulate ciprofloxacin (CIP in solid lipid nanoparticles (SLNs in an attempt to develop a controlled drug delivery system. An ultrasonic melt-emulsification method was used for preparing CIP-loaded SLNs. Key findings included that SLNs were successfully produced with average particle sizes ranging from 165 to 320 nm and polydispersity index in the range of 0.18–0.33. High entrapment efficiency values were reported in all formulations. The atomic force scanning microscopic images showed spherical shape with the size range closer to those found by the particle size analyzer. CIP release exhibited controlled-release behavior with various lipids. Ciprofloxacin solid lipid nanoparticles formula containing stearic acid (CIPSTE displayed the strongest burst effect and the most rapid release rate. The release data revealed a better fit to the Higuchi diffusion model. After storing the CIPSTE formula at room temperature for 120 days, no significant difference in particle size and zeta potential was found. CIP-loaded SLNs exhibited superior antibacterial activity. Incorporation of CIP into SLNs leads to controlled release and a superior antibacterial effect of CIP.

  10. Controlled release of insect sex pheromones from paraffin wax and emulsions.

    Science.gov (United States)

    Atterholt, C A; Delwiche, M J; Rice, R E; Krochta, J M

    1999-02-22

    Paraffin wax and aqueous paraffin emulsions can be used as controlled release carriers for insect sex pheromones for mating disruption of orchard pests. Paraffin can be applied at ambient temperature as an aqueous emulsion, adheres to tree bark or foliage, releases pheromone for an extended period of time, and will slowly erode from bark and biodegrade in soil. Pheromone emulsions can be applied with simple spray equipment. Pheromone release-rates from paraffin were measured in laboratory flow-cell experiments. Pheromone was trapped from an air stream with an adsorbent, eluted periodically, and quantified by gas chromatography. Pheromone release from paraffin was partition-controlled, providing a constant (zero-order) release rate. A typical paraffin emulsion consisted of 30% paraffin, 4% pheromone, 4% soy oil, 1% vitamin E, 2% emulsifier, and the balance water. Soy oil and vitamin E acted as volatility suppressants. A constant release of oriental fruit moth pheromone from paraffin emulsions was observed in the laboratory for more than 100 days at 27 degreesC, with release-rates ranging from 0.4 to 2 mg/day, depending on the concentration and surface area of the dried emulsion. The use of paraffin emulsions is a viable method for direct application of insect pheromones for mating disruption. Sprayable formulations can be designed to release insect pheromones to the environment at a rate necessary for insect control by mating disruption. At temperatures below 38 degreesC, zero-order release was observed. At 38 degreesC and higher, pheromone oxidation occurred. A partition-controlled release mechanism was supported by a zero-order pheromone release-rate, low air/wax partition coefficients, and pheromone solubility in paraffin.

  11. Environmental Release Prevention and Control Plan

    Energy Technology Data Exchange (ETDEWEB)

    Mamatey, A.; Arnett, M.

    1997-10-01

    During the history of SRS, continual improvements in facilities, process, and operations, and changes in the site`s mission have reduced the amount of radioactive liquid releases. In the early years of SRS (1958 to 1965), the amount of tritium discharged to the Savannah River averaged approximately 61,000 curies a year. During the mid-1980`s (1983 to 1988), liquid releases of tritium averaged 27,000 curies a year. By 1996, liquid releases of tritium are projected to be just 3000 curies for the year. This large projected decrease is the result of the planned shut-down of all reactors and the anticipated significant decline in the amount of tritium migrating from the site seepage basins and the Solid Waste Disposal Facility.

  12. Bioequivalence of Sandoz methylphenidate osmotic-controlled release tablet with Concerta® (Janssen-Cilag)

    OpenAIRE

    Schapperer, Elisabeth; Daumann, Heike; Lamouche, Stéphane; Thyroff-Friesinger, Ursula; Viel, François; Weitschies, Werner

    2015-01-01

    The aim was to assess the bioequivalence of Sandoz methylphenidate osmotic-controlled release (OCR) tablets (Sandoz [Methylphenidate[ MPH OCR) with Concerta®, a methylphenidate formulation indicated for the treatment of attention deficit/hyperactivity disorder (ADHD). Four open-label, randomized, single-dose, two-way crossover bioequivalence studies were conducted in healthy subjects: three fasting studies with 54-, 36- and 18-mg doses of methylphenidate, and one fed study with the 54-mg dose...

  13. Solid lipid nanoparticles (SLN) for controlled drug delivery--drug release and release mechanism.

    Science.gov (United States)

    zur Mühlen, A; Schwarz, C; Mehnert, W

    1998-03-01

    Solid lipid nanoparticles (SLN) are particulate systems for parenteral drug administration with mean particle diameters ranging from 50 up to 1000 nm. The model drugs tetracaine, etomidate and prednisolone were incorporated (1, 5 and 10%) to study the drug load, effect of drug incorporation on the structure of the lipid matrix and the release profiles and mechanism. SLN were produced by high pressure homogenization of aqueous surfactant solutions containing the drug-loaded lipids in the melted or in the solid state (500/1500 bar, 3/10 cycles). In case of tetracaine and etomidate, high drug loadings up to 10% could be achieved when using Compritol 888 ATO and Dynasan 112 as matrix material. The melting behavior of the drug loaded particles revealed that little or no interactions between drug and lipid occurred. A burst drug release (100% release < 1 min) was observed with tetracaine and etomidate SLN, which was attributed to the large surface area of the nanoparticles and drug enrichment in the outer shell of the particles. In contrast, prednisolone loaded SLN showed a distinctly prolonged release over a monitored period of 5 weeks. Depending on the chemical nature of the lipid matrix, 83.8 and 37.1% drug were released (cholesterol and compritol, respectively). These results demonstrate the principle suitability of SLN as a prolonged release formulation for lipophilic drugs.

  14. 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.

  15. Overview study of LNG release prevention and control systems

    Energy Technology Data Exchange (ETDEWEB)

    Pelto, P.J.; Baker, E.G.; Holter, G.M.; Powers, T.B.

    1982-03-01

    The liquefied natural gas (LNG) industry employs a variety of release prevention and control techniques to reduce the likelihood and the consequences of accidental LNG releases. A study of the effectiveness of these release prevention and control systems is being performed. Reference descriptions for the basic types of LNG facilities were developed. Then an overview study was performed to identify areas that merit subsequent and more detailed analyses. The specific objectives were to characterize the LNG facilities of interest and their release prevention and control systems, identify possible weak links and research needs, and provide an analytical framework for subsequent detailed analyses. The LNG facilities analyzed include a reference export terminal, marine vessel, import terminal, peakshaving facility, truck tanker, and satellite facility. A reference description for these facilities, a preliminary hazards analysis (PHA), and a list of representative release scenarios are included. The reference facility descriptions outline basic process flows, plant layouts, and safety features. The PHA identifies the important release prevention operations. Representative release scenarios provide a format for discussing potential initiating events, effects of the release prevention and control systems, information needs, and potential design changes. These scenarios range from relatively frequent but low consequence releases to unlikely but large releases and are the principal basis for the next stage of analysis.

  16. Novel topical formulation for ischemic chronic wounds. Technological design, quality control and safety evaluation.

    Science.gov (United States)

    Cabrera, Carla Agostina; Ramos, Alberto Nicolas; Loandos, María Del Huerto; Valdez, Juan Carlos; Sesto Cabral, Maria Eugenia

    2016-01-01

    Ulceration of the foot in diabetes is common and disabling, and frequently leads to amputation of the leg. The pathogenesis of foot ulceration is complex, clinical presentation variable and management requires early expert assessment. Despite treatment, ulcers readily become chronic wounds. Chronic wounds are those that remain in a chronic inflammatory state failing a normal healing process patterns. This is partially caused by inefficient eradication of opportunistic pathogens like Pseudomonas aeruginosa. We propose its control or eradication will promote wound healing. Lactobacillus plantarum cultures supernatants (LAPS) shows antipathogenic and pro-healing properties. The main objective was to design two pharmaceutical dosage forms by using LAPS as active pharmaceutical ingredient and to perform its quality control, in vitro activity conservation tests and human trials (safety evaluation). Both selected formulations reach the technological quality expected for 120 days, shows adequate occlusive characteristics and proper adhesion to human skin. From the in vitro release assays were found that LAPS shows adequate release from matrix and maintain its antimicrobial and anti-biofilm activity. First human trials were developed and neither edema nor erythema on healthy skin voluntaries was found. We conclude that C80 and C100 are adequate for their use in future clinical trials to demonstrate a comprehensive therapeutic effectiveness in ischemic chronic wounds.

  17. Formulation and Characterization of Matrix and Triple-Layer matrix tablets for Controlled Delivery of Metoprolol tartrate

    Directory of Open Access Journals (Sweden)

    Izhar Ahmed Syed

    2011-01-01

    Full Text Available In the present study matrix and triple layer matrix tablets of metoprolol tartrate were formulated by using xanthan gum as the matrix forming agent and Sodium Carboxy Methyl Cellulose (Na CMC as barrier layers. The prepared tablets were analysed for their hardness, friability, drug content and in-vitro drug release studies. Marked differences in dissolution characteristics of (M3 and (M3L3 were observed and showed a significant difference statistically. Mean dissolution time (MDT for M3 and M3L3 were found to be 4.02h and 12.75h, while dissolution efficiency (DE8% decreased, indicating that the release of metoprolol tartrate is slower from triple layer matrix tablets. The finding of the study indicated that the matrix tablets prolonged the release, but predominantly in a first order kinetics. Layering with Na CMC granules on the matrix core, provided linear drug release with zero order kinetics. The triple layer matrix tablets (M3L3 shows precise controlled release of the drug than that of plain matrix tablets. FT-IR and DSC studies confirmed that there was no chemical interaction between drug and excipients used in the formulation.

  18. Novel gastroretentive controlled-release drug delivery system for amoxicillin therapy in veterinary medicine.

    Science.gov (United States)

    Horwitz, E; Kagan, L; Chamisha, Y; Gati, I; Hoffman, A; Friedman, M; Lavy, E

    2011-10-01

    Beta-lactam antimicrobials, commonly used in both veterinary and human medicine, generally present short biologic half-lives, whereas their activity is enhanced as pathogen exposure is prolonged. These properties necessitate multiple-dose regimens of standard dosage forms, thereby hampering pet owner adherence, frequently resulting in therapeutic failure. This study presents a novel controlled-release gastroretentive oral drug delivery system for beta-lactams with which single-dose administration provides an effective antimicrobial course, optimizing pharmacokinetic (PK)-pharmacodynamic (PD) profiles, minimizing adverse effects and emergence of antimicrobial resistance and facilitating adherence. Our prototype sustained-delivery swelling-tablet (SDST), based on a degradable hydrophilic polymeric matrix, was designed to enable continuous input of these drugs to their absorption sites over several days. Several SDST formulations of the beta-lactam amoxicillin were evaluated in in vitro dissolution studies. Two formulations were selected for further in vivo canine studies, for determination of gastric retention and PK-PD profiling. Prolonged gastric retention times maintaining allowed for maintained effective drug concentrations against many clinically relevant pathogens for more than 48 h for one formulation and more than 5 days for the other. Both SDST formulations offer significant advantages over standard immediate-release therapy in achieving PK-PD goals and enhancing adherence. The prototypical formulations represent a novel platform which may be modified to meet various clinical requirements. © 2010 Blackwell Publishing Ltd.

  19. 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

  20. 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.

  1. Preparation and characterization of controlled-release fertilizers coated with marine polysaccharide derivatives

    Science.gov (United States)

    Wang, Jing; Liu, Song; Qin, Yukun; Chen, Xiaolin; Xing, Rong'e.; Yu, Huahua; Li, Kecheng; Li, Pengcheng

    2017-09-01

    Encapsulation of water-soluble nitrogen fertilizers by membranes can be used to control the release of nutrients to maximize the fertilization effect and reduce environmental pollution. In this research, we formulated a new double-coated controlled-release fertilizer (CRF) by using food-grade microcrystalline wax (MW) and marine polysaccharide derivatives (calcium alginate and chitosan-glutaraldehyde copolymer). The pellets of water-soluble nitrogen fertilizer were coated with the marine polysaccharide derivatives and MW. A convenient and eco-friendly method was used to prepare the CRF. Scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR) were used to characterize the morphology and composition of the products. The nitrogen-release properties were determined in water using UV-Vis spectrophotometry. The controlled-release properties of the fertilizer were improved dramatically after coating with MW and the marine polysaccharide derivatives. The results show that the double-coated CRFs can release nitrogen in a controlled manner, have excellent controlled-release features, and meet the European Standard for CRFs.

  2. Preparation and characterization of controlled-release fertilizers coated with marine polysaccharide derivatives

    Science.gov (United States)

    Wang, Jing; Liu, Song; Qin, Yukun; Chen, Xiaolin; Xing, Rong'e.; Yu, Huahua; Li, Kecheng; Li, Pengcheng

    2016-10-01

    Encapsulation of water-soluble nitrogen fertilizers by membranes can be used to control the release of nutrients to maximize the fertilization effect and reduce environmental pollution. In this research, we formulated a new double-coated controlled-release fertilizer (CRF) by using food-grade microcrystalline wax (MW) and marine polysaccharide derivatives (calcium alginate and chitosan-glutaraldehyde copolymer). The pellets of water-soluble nitrogen fertilizer were coated with the marine polysaccharide derivatives and MW. A convenient and eco-friendly method was used to prepare the CRF. Scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR) were used to characterize the morphology and composition of the products. The nitrogen-release properties were determined in water using UV-Vis spectrophotometry. The controlled-release properties of the fertilizer were improved dramatically after coating with MW and the marine polysaccharide derivatives. The results show that the double-coated CRFs can release nitrogen in a controlled manner, have excellent controlled-release features, and meet the European Standard for CRFs.

  3. 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 ...

  4. 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

  5. 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.

  6. 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.

  7. Controlled release of verapamil hydrochloride from waxy microparticles prepared by spray congealing.

    Science.gov (United States)

    Passerini, Nadia; Perissutti, Beatrice; Albertini, Beatrice; Voinovich, Dario; Moneghini, Mariarosa; Rodriguez, Lorenzo

    2003-03-01

    In this work, the potential of waxes for preparing with the ultrasonic spray congealing technique microparticles for controlling the in vitro release of verapamil HCl was investigated. The first part of the study encompassed the optimisation of the formulation to achieve an efficient drug incorporation together with a satisfactory in vitro drug release rate. In particular, microcrystalline wax, stearyl alcohol and mixtures of the two were used. Also a surfactant (soya lecithin) was added to the formulations. After the particle size analysis, the characterisation of the microparticles involved the study of the solid state of drug and carriers in the systems (DSC, HSM and XRD) and the morphological and chemical analyses of the microparticle surface (SEM and XPS). Finally, the drug release mechanism from these devices was evaluated using the statistical moment analysis. The results of this study show that by selecting the type and the amount of the carriers, microparticles with a spherical shape and a good encapsulation efficiency were observed. These particles showed a zero-order release for 8 h, without modifying the solid state properties of the drug. Therefore, waxy microparticles prepared by the ultrasonic spray congealing technique are promising solvent-free devices for controlling the release of verapamil HCl.

  8. Preparation and characterization of metoprolol controlled-release solid dispersions.

    Science.gov (United States)

    Varshosaz, Jaleh; Faghihian, Hossein; Rastgoo, Kobra

    2006-01-01

    In recent years, great attention has been paid to using solid dispersions to make sustained-release drugs. The objective of this study is to produce sustained-release systems of metoprolol tartrate using solid dispersion techniques and to evaluate their physicochemical characteristics. The solid dispersions were produced by melting and solvent methods, containing 7%, 15%, or 25% of the drug and different ratios of Eudragit RLPO and RSPO in ratios of 0:10, 3:7, 5:5, 7:3, and 10:0. Drug release profiles were determined by USP XXIII rotating paddle method in phosphate buffer solution (pH 6.8). XRD, DSC, IR, and microscopic observations were performed to evaluate the physical characteristics of solid dispersions. Results showed that the drug release from dispersions was at a slower rate than pure drug and physical mixtures. Moreover, the formulations containing greater ratios of Eudragit RSPO showed slower release rates and smaller DE8% but larger mean dissolution time than those containing greater ratios of Eudragit RLPO. Dispersions with particle size of less than 100 microm containing 7% of metoprolol and Eudragit RL:RS 5:5 (solvent method) and those with the ratio of 3:7 (melting method) had similar release pattern to Lopressor sustained-release tablets by zero-order and Higuchi kinetics, respectively.

  9. 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.

  10. 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.

  11. 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.

  12. Controlled-release Properties of Microencapsulated Disperse Dyes

    Institute of Scientific and Technical Information of China (English)

    LUO Yan; LI Chun-yan; CHEN Shui-lin

    2002-01-01

    Some disperse dyes were microencapsulated by means of in- situ polymerization. These microencapsulated disperse dyes was extracted respectively by ethanol under certain conditions. The controlled-release properties of disperse dyes through the shell of microcapsules were measured by spectrophotometer. According to the results, it was drawn that the type of disperse dyes, the auxiliaries contained in disperse dyes, the quantity of system controlling medium used and the core/shell ratio of microcapsules play important roles in controlling the release properties of microcapsules. The different controlled- release properties of microcapsules, which were prepared under given conditions, however, would in turn influence the performance of microcapsules in multiple-transfer printing.

  13. Optimal Release Control of Companion Satellite System Using Electromagnetic Forces

    Institute of Scientific and Technical Information of China (English)

    Zengwen Xu,Peng Shi; Yushan Zhao∗

    2015-01-01

    Electromagnetic forces generated by the inter⁃action of component satellites can be used to release companion satellites. Optimal release trajectories for companion satellite system using inter⁃electromagnetic forces were investigated. Firstly, nonlinear relative motion dynamic equations of a two⁃craft electromagnetic companion satellite system were derived in spatial polar coordinates. Then principles of electromagnetic satellite formation flying were introduced. Secondly, the characteristics of the electromagnetic companion satellites release were analyzed and optimal release trajectories of companion satellites using electromagnetic forces were obtained using Gauss pseudospectral method. Three performance criteria were chosen as minimum time, minimum acceleration of the separation distance and minimum control acceleration. Finally, three release examples including expansion along separation distance, rotation in orbital plane and stable formation reconfiguration were given to demonstrate the feasibility of this method. Results indicated that the release trajectories can converge to optimal solutions effectively and the concept of release companion satellites using electromagnetic forces is practicable.

  14. 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.

  15. 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.

  16. Release and control of hydrogen sulfide during sludge thermal drying

    Energy Technology Data Exchange (ETDEWEB)

    Weng, Huanxin; Dai, Zhixin; Ji, Zhongqiang; Gao, Caixia; Liu, Chongxuan

    2015-04-15

    The release of hydrogen sulfide (H2S) during sludge drying is a major environmental problem because of its toxicity to human health. A series of experiments were performed to investigate the mechanisms and factors controlling the H2S release. Results of this study show that: 1) the biomass and activity of sulfate-reducing bacteria (SRB) in sludge were the major factors controlling the amount of H2S release, 2) the sludge drying temperature had an important effect on both the extent and the timing of H2S release from the sludge, and 3) decreasing sludge pH increased the H2S release. Based on the findings from this study, a new system that integrates sludge drying and H2S gas treatment was developed to reduce the amount of H2S released from sludge treatments.

  17. Controlled-release fluvoxamine in obsessive-compulsive disorder and social phobia.

    Science.gov (United States)

    Owen, Richard T

    2008-12-01

    Specific serotonin reuptake inhibitors are currently recommended as first-line treatments for obsessive-compulsive disorder (OCD) and social phobia or social anxiety disorder (SAD). Fluvoxamine has demonstrated efficacy in both these conditions and has recently been marketed in a controlled-release (CR) formulation in the United States for treatement of OCD and SAD. Three 12-week double-blind, multicenter, randomized, placebo-controlled studies were conducted with this formulation - two in SAD and one in OCD. All three studies showed a robust effect on the key symptoms of OCD and SAD and had broadly comparable efficacy to studies conducted with immediate-release (IR) fluvoxamine. The beneficial effects of fluvoxamine CR were maintained in a 12-week double-blind, randomized extension to one SAD trial. The CR formulation, when compared to its IR counterpart, offers less daily fluctuation in fluvoxamine levels and a more rapid titration schedule; in addition, a more rapid onset of effect may result from these features. Overall, the benefits of the CR formulation, among them the convenience of oncedaily dosing, were achieved without an increased adverse event burden versus the IR form.

  18. 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.

  19. Qualitative analysis of controlled release ciprofloxacin/carbopol 934 mucoadhesive suspension

    Directory of Open Access Journals (Sweden)

    Subhashree Sahoo

    2011-01-01

    Full Text Available Mucoadhesive polymeric (carbopol 934 suspension of ciprofloxacin was prepared by ultrasonication and optimized with the aim of developing an oral controlled release gastro-retentive dosage form. The qualitative analysis of the formulation was performed by fourier transform infrared spectroscopy (FTIR, Raman spectroscopy, X-ray powder diffraction (XRD, and scanning electron microscopy (SEM analyses. FTIR (400 cm-1 to 4000 cm-1 region and Raman (140 to 2400 cm-1 region Spectroscopic studies were carried out and the spectra were used for interpretation. XRD data of pure drug, polymer and the formulation were obtained using a powder diffractometer scanned from a Bragg′s angle (2q of 10° to 70°. The dispersion of the particle was observed using SEM techniques. The particle size distribution and aspect ratio of particles in the polymeric suspension were obtained from SEM image analysis. The results from FTIR and Raman spectroscopic analyses suggested that, in formulation, the carboxylic groups of ciprofloxacin and hydroxyl groups of C934 undergo a chemical interaction leading to esterification and hydrogen bonding. The XRD data suggested that the retention of crystalline nature of ciprofloxacin in the formulation would lead to increase in stability and drug loading; decrease in solubility; and delay in release of the drug from polymeric suspension with better bioavailability and penetration capacity. The SEM image analysis indicated that, in the formulation maximum particles were having aspect ratio from 2 to 4 and standard deviation was very less which provided supporting evidences for homogeneous, uniformly dispersed, stable controlled release ciprofloxacin suspension which would be pharmaceutically acceptable.

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

    Directory of Open Access Journals (Sweden)

    Bhagwat Durgacharan

    2009-01-01

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

  1. 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.

  2. 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.

  3. Best Practices for Controlling Lead and Copper Release

    Science.gov (United States)

    Presentation draft, covering summary of current state-of-the-art knowledge for the best treatment strategies for minimizing lead release and controlling copper release. The presentation is intended to aid with compliance with the Lead and Copper Rule, but also provide a guide to...

  4. Chitosan-polycarbophil complexes in swellable matrix systems for controlled drug release.

    Science.gov (United States)

    Lu, Z; Chen, W; Hamman, J H

    2007-10-01

    A prerequisite for progress in the design of novel drug delivery systems is the development of excipients that are capable of fulfilling multifunctional roles such as controlling the release of the drug according to the therapeutic needs. Although several polymers have been utilised in the development of specialised drug delivery systems, their scope in dosage form design can be enlarged through combining different polymers. When a polymer is cross-linked or complexed with an oppositely charged polyelectrolyte, a three-dimensional network is formed in which the drug can be incorporated to control its release. The swelling properties and release kinetics of two model drugs with different water solubilities (i.e. diltiazem and ibuprofen) from monolithic matrix tablets consisting of an interpolyelectrolyte complex between chitosan and polycarbophil are reported. Matrix tablets consisting of this polymeric complex without drug or excipients exhibited extremely high swelling properties that are completely reversible upon drying. The drug release from matrix systems with different formulations depended on the concentration of the chitosan-polycarbophil interpolyelectrolyte complex and approached zero order release kinetics for both model drugs. The chitosan-polycarbophil interpolyelectrolyte complex has demonstrated a high potential as an excipient for the production of swellable matrix systems with controlled drug release properties.

  5. 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.

  6. 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.

  7. 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

  8. Photoresponsive lipid-polymer hybrid nanoparticles for controlled doxorubicin release

    Science.gov (United States)

    Yao, Cuiping; Wu, Ming; Zhang, Cecheng; Lin, Xinyi; Wei, Zuwu; Zheng, Youshi; Zhang, Da; Zhang, Zhenxi; Liu, Xiaolong

    2017-06-01

    Currently, photoresponsive nanomaterials are particularly attractive due to their spatial and temporal controlled drug release abilities. In this work, we report a photoresponsive lipid-polymer hybrid nanoparticle for remote controlled delivery of anticancer drugs. This hybrid nanoparticle comprises three distinct functional components: (i) a poly(D,L-lactide-co-glycolide) (PLGA) core to encapsulate doxorubicin; (ii) a soybean lecithin monolayer at the interface of the core and shell to act as a molecular fence to prevent drug leakage; (iii) a photoresponsive polymeric shell with anti-biofouling properties to enhance nanoparticle stability, which could be detached from the nanoparticle to trigger the drug release via a decrease in the nanoparticle’s stability under light irradiation. In vitro results revealed that this core-shell nanoparticle had excellent light-controlled drug release behavior (76% release with light irradiation versus 10% release without light irradiation). The confocal microscopy and flow cytometry results also further demonstrated the light-controlled drug release behavior inside the cancer cells. Furthermore, a CCK8 assay demonstrated that light irradiation could significantly improve the efficiency of killing cancer cells. Meanwhile, whole-animal fluorescence imaging of a tumor-bearing mouse also confirmed that light irradiation could trigger drug release in vivo. Taken together, our data suggested that a hybrid nanoparticle could be a novel light controlled drug delivery system for cancer therapy.

  9. Formulation and Evaluation of Controlled Porosity Osmotic Pump Tablet of Zaltoprofen

    Directory of Open Access Journals (Sweden)

    Jadav Mukesh M.

    2012-05-01

    Full Text Available Zaltoprofen is a non steroidal anti inflammatory class of drug which has excellent effect on post-surgeryor post trauma chronic inflammation of the drug. So, Zaltoprofen may serve as a potent and superioranalgesic for the treatment of pain. Zaltoprofen has the dose of 80 mg three times a day which reducepatient compliance. For that in this present study, an attempt has been made to prepare the controlledrelease CPOP tablet twice a day. An inclusion complex was prepared by kneading method using HP-β-CD in order to increase solubility of the poorly water soluble drug. Then, this complex is used forpreparing the tablet with accessorial material. CPOP tablet containing Zaltoprofen were prepared bydirect compression method by using various osmotic agent like sodium bicarbonate, sodium chloride,mannitol and potassium carbonate. Cellulose acetate, Sorbitol and Poly Ethylene Glycol 400 wereselected for coating materials, and acetone: methanol (65:35 co-solvent was employed as the coatingmedium with 3% and 5% weight gain. Initially compatibility study was carried out using DSC and FTIRSpectrometric method. The blend was examined for pre-compression parameters like angle of repose,density, compressibility index and Hausner’s ratio. Formulated tablet also passes the various tabletparameters like hardness, friability, drug content, weight variation. From the result of in-vitro drugrelease study it was observed that as the amount of osmotic agent increased, amount of drug releaseincreased. Also increased in % weight gain decreased the % drug release. Batch Z4 containing sodiumbicarbonate as osmotic agent has shown 98.08% drug release compare to other batches so, accepted asoptimized batch. The above optimized batch Z4 was also evaluated by different pharmacokinetic modelslike Zero order, First order, Higuchi, Korsmeyer Peppas, and Hixson Crowell model. The results ofthese models have shown that the batch Z4 controls the drug release for 12 hr and follows

  10. Trigger release liposome systems: local and remote controlled delivery?

    Science.gov (United States)

    Bibi, Sagida; Lattmann, E; Mohammed, Afzal R; Perrie, Yvonne

    2012-01-01

    Target-specific delivery has become an integral area of research in order to increase bioavailability and reduce the toxic effects of drugs. As a drug-delivery option, trigger-release liposomes offer sophisticated targeting and greater control-release capabilities. These are broadly divided into two categories; those that utilise the local environment of the target site where there may be an upregulation in certain enzymes or a change in pH and those liposomes that are triggered by an external physical stimulus such as heat, ultrasound or light. These release mechanisms offer a greater degree of control over when and where the drug is released; furthermore, targeting of diseased tissue is enhanced by incorporation of target-specific components such as antibodies. This review aims to show the development of such trigger release liposome systems and the current research in this field.

  11. Nutrients Release from a Novel Gel-Based Slow/Controlled Release Fertilizer

    OpenAIRE

    Ding, H.; Y. S. Zhang; Li, W. H.; Zheng, X. Z.; Wang, M. K.; Tang, L. N.; Chen, D. L.

    2016-01-01

    A novel gel-based slow/controlled release fertilizer (G-CRF) was developed, which was produced by combining various natural, seminatural, and/or synthetic organic macromolecule materials and natural inorganic mineral with conventional NPK fertilizers. Its nutrient release characteristics were studied to compare with conventional fertilizers through the soil column leaching method. The influences of soil factors, including temperature, pH, water, and nutrient contents in the G-CRF on nutrient ...

  12. Controlling Liquid Release by Compressing Electrospun Nanowebs

    Directory of Open Access Journals (Sweden)

    K.G. Kornev

    2009-09-01

    Full Text Available Electrospun nanowebs with pores ranging from nanometers to micrometers, constitute new materials with enhanced absorbency and ability to retain liquids in pores for a long period of time. These materials can be used as nanofluidic probes collecting minute amount of liquids. However, extraction of liquids from nanofibrous materials presents a problem: menisci in the interfiber pores create very high suction pressure which holds the liquid inside the material. This problem can be resolved if the probe is completely filled with the liquid: menisci at the probe edges become flat to establish a pressure equilibrium with the atmosphere. Therefore, one can take advantage of the nanoweb softness and extract liquid by mechanically deforming the nanowebs. We show that the liquid-saturated nanowebs follow the Voigt-type rheology upon loading. We theoretically explain this behavior and derive the relations between the Voigt phenomenological parameters, nanoweb permeability and compression modulus. We show that the limiting deformations follow the Hooke’s law which assumes linear relation between the extracted volume of liquid and the applied load. Because of this predictable behavior, the nanoweb probes can be engineered to release minute liquid doses upon compression. The developed experimental methodology can be used for characterization of nanostructured materials which otherwise impossible to analyze by using the existing instruments.

  13. Formulation, quality control and shelf life of the experimental cytostatic drug cyclopentenyl cytosine

    NARCIS (Netherlands)

    K. Schimmel; H.J. Guchelaar; E. van Kan

    2006-01-01

    This paper describes the formulation and quality control of an aqueous sterilized formulation of the experimental cytostatic drug cyclopentenyl cytosine (CPEC) to be used in Phase I/II clinical trials. The raw drug substance was extensively tested. A High Pressure Liquid Chromotography (HPLC) method

  14. Nanoporous Silicified Phospholipids and Application to Controlled Glycolic Acid Release

    Directory of Open Access Journals (Sweden)

    Kang SangHwa

    2008-01-01

    Full Text Available Abstract This work demonstrates the synthesis and characterization of novel nanoporous silicified phospholipid bilayers assembled inorganic powders. The materials are obtained by silicification process with silica precursor at the hydrophilic region of phospholipid bilayers. This process involves the co-assembly of a chemically active phospholipids bilayer within the ordered porosity of a silica matrix and holds promise as a novel application for controlled drug release or drug containers with a high level of specificity and throughput. The controlled release application of the synthesized materials was achieved to glycolic acid, and obtained a zero-order release pattern due to the nanoporosity.

  15. [Drug release system controlled by near infrared light].

    Science.gov (United States)

    Niidome, Takuro

    2013-01-01

    Gold nanorods have absorption bands in the near-infrared region; in this spectral range, light penetrates deeply into tissues. The absorbed light energy is converted into heat by gold nanorods. This is the so-called photothermal effect. Gold nanorods are therefore expected to act not only as thermal converters for photothermal therapy, but also as controllers for drug-release systems responding to irradiation with near-infrared light. To achieve a controlled-release system that could be triggered by light irradiation, the gold nanorods were modified with double-stranded DNA (dsDNA). When the dsDNA-modified gold nanorods were irradiated with near-infrared light, single-stranded DNA (ssDNA) was released from the gold nanorods because of the photothermal effect. The release of ssDNA was also observed in tumors grown on mice after near-infrared light irradiation. We also proposed a different controlled-release system responding to near-infrared light. Gold nanorods were modified with polyethylene glycol (PEG) through Diels-Alder cycloadducts. When the gold nanorods were irradiated with near-infrared light, the PEG chains were released from the gold nanorods because of the retro Diels-Alder reaction induced by the photothermal effect. Such controlled-release systems triggered by near-infrared light irradiation will be expanded for gold nanorod drug delivery system applications.

  16. "Rolling" phenomenon in twin screw granulation with controlled-release excipients.

    Science.gov (United States)

    Thompson, M R; O'Donnell, K P

    2015-03-01

    The developed knowledge regarding use of twin screw granulators for continuous wet granulation has been primarily limited to immediate release formulations in the literature. The present study highlights an issue previously unreported for wet granulation with twin screw extruders when using formulations containing controlled-release (CR) excipients. Long (3-10 mm), twisted noodle-like granules can be produced in the presence of these excipients that are difficult to control and are anticipated to create complications in downstream unit operations to the granulator. Working with two different CR excipients, METHOCEL™ K4M and Kollidon® SR, each blended at different ratios with a mixture of 80% α-lactose monohydrate/20% microcrystalline cellulose, these unique particles were found to be produced in the conveying elements of the extruder, arising from a rolling action at the top of the screw flights. The CR excipients adhesively strengthen the wetted mass, forming this undesired granule shape such that they persisted to the exit of the machine; the shape appeared most strongly affected by screw speed, producing particles of higher aspect ratio as speed was increased. Adjusting the concentration of these CR excipients in the formulation, the flow rate or the type of compression element used in the screws proved ineffective in controlling the problem. Rather, a re-design of the extruder screws was required to prevent generation of these extended-form granules.

  17. Hydrogels containing redispersible spray-dried melatonin-loaded nanocapsules: a formulation for transdermal-controlled delivery

    Science.gov (United States)

    Hoffmeister, Cristiane RD; Durli, Taís L.; Schaffazick, Scheila R.; Raffin, Renata P.; Bender, Eduardo A.; Beck, Ruy CR; Pohlmann, Adriana R.; Guterres, Sílvia S.

    2012-05-01

    The aim of the present study was to develop a transdermal system for controlled delivery of melatonin combining three strategies: nanoencapsulation of melatonin, drying of melatonin-loaded nanocapsules, and incorporation of nanocapsules in a hydrophilic gel. Nanocapsules were prepared by interfacial deposition of the polymer and were spray-dried using water-soluble excipients. In vitro drug release profiles were evaluated by the dialysis bag method, and skin permeation studies were carried out using Franz cells with porcine skin as the membrane. The use of 10% ( w/ v) water-soluble excipients (lactose or maltodextrin) as spray-drying adjuvants furnished redispersible powders (redispersibility index approximately 1.0) suitable for incorporation into hydrogels. All formulations showed a better controlled in vitro release of melatonin compared with the melatonin solution. The best controlled release results were achieved with hydrogels prepared with dried nanocapsules (hydrogels > redispersed dried nanocapsules > nanocapsule suspension > melatonin solution). The skin permeation studies demonstrated a significant modulation of the transdermal melatonin permeation for hydrogels prepared with redispersible nanocapsules. In this way, the additive effect of the different approaches used in this study (nanoencapsulation, spray-drying, and preparation of semisolid dosage forms) allows not only the control of melatonin release, but also transdermal permeation.

  18. Design and evaluation of osmotic pump-based controlled release system of Ambroxol Hydrochloride.

    Science.gov (United States)

    Cheng, Xiongkai; Sun, Min; Gao, Yan; Cao, Fengliang; Zhai, Guangxi

    2011-08-01

    The purpose of the present study was to design and evaluate an osmotic pump-based drug delivery system for controlling the release of Ambroxol Hydrochloride (Amb). Citric acid, lactose and polyethylene glycol 6000 (PEG 6000) were employed as osmotic agents. Surelease EC containing polyethylene glycol 400 (PEG 400) controlling the membrane porosity was used as semi-permeable membrane. The formulation of tablet core was optimized by orthogonal design and evaluated by weighted mark method. The influences of the amount of PEG 400 and membrane thickness on Amb release were investigated. The optimal osmotic pump tablet (OPT) was evaluated in different release media and at different stirring rates. The major release power confirmed was osmotic pressure. The release of Amb from OPT was verified at a rate of approximately zero-order, and cumulative release percentage at 12?h was 92.6%. The relative bioavailability of Amb OPT in rabbits relative to the commercial sustained capsule was 109.6%. Our results showed that Amb OPT could be a practical preparation with a good prospect.

  19. Preparation and evaluation of waxes/fat microspheres loaded with lithium carbonate for controlled release

    Directory of Open Access Journals (Sweden)

    Gowda D

    2007-01-01

    Full Text Available To minimize the unwanted toxic effects of anti maniac drug lithium carbonate by kinetic control of drug release, it was entrapped into gastro resistant, biodegradable, waxes and fat such as beeswax, cetostearyl alcohol, spermaceti and cetylalcohol microspheres using meltable emulsified dispersion cooling induced solidification technique utilizing a wetting agent. Solid, discrete, reproducible free flowing microspheres were obtained. The yield of the microspheres was up to 90.0%. More than 98.0% of the isolated microspheres were of particle size range 115 to 855 mm. The microspheres had smooth surfaces, with free flowing and good packing properties. Scanning electron microscope confirmed their spherical structures within a size range of 339-355 mm. The drug loaded in waxes and fat microspheres was stable and compatible, as confirmed by DSC and FTIR studies. The release of drug was controlled for more than 8 hours. Intestinal drug release from waxes/ fat microspheres was studied and compared with the releases behavior of commercially available formulation Intalith CR ®-450. The release kinetics followed different transport mechanisms. The drug release performance was greatly affected by the materials used in microsphere preparations, which allows absorption in the intestinal tract.

  20. 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.

  1. Fabrication of ultrathin polyelectrolyte fibers and their controlled release properties.

    Science.gov (United States)

    Chunder, Anindarupa; Sarkar, Sourangsu; Yu, Yingbo; Zhai, Lei

    2007-08-01

    Ultrathin fibers comprising 2-weak polyelectrolytes, poly(acrylic acid) (PAA) and poly(allylamine hydrochloride) (PAH) were fabricated using the electrospinning technique. Methylene blue (MB) was used as a model drug to evaluate the potential application of the fibers for drug delivery. The release of MB was controlled in a nonbuffered medium by changing the pH of the solution. The sustained release of MB in a phosphate buffered saline (PBS) solution was achieved by constructing perfluorosilane networks on the fiber surfaces as capping layers. Temperature controlled release of MB was obtained by depositing temperature sensitive PAA/poly(N-isopropylacrylamide) (PNIPAAM) multilayers onto the fiber surfaces. The controlled release of drugs from electrospun fibers have potential applications as drug carriers in biomedical science.

  2. 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.

  3. Controlled release implants based on cast lipid blends.

    Science.gov (United States)

    Kreye, F; Siepmann, F; Zimmer, A; Willart, J F; Descamps, M; Siepmann, J

    2011-05-18

    The aim of this study was to use lipid:lipid blends as matrix formers in controlled release implants. The systems were prepared by melting and casting and thoroughly characterized before and after exposure to the release medium. Based on the experimental results, a mechanistic realistic mathematical model was used to get further insight into the underlying drug release mechanisms. Importantly, broad spectra of drug release patterns could be obtained by simply varying the lipid:lipid blend ratio in implants based on Precirol ATO 5 (glyceryl palmitostearate):Dynasan 120 (hardened soybean oil) mixtures loaded with propranolol hydrochloride. Release periods ranging from a few days up to several months could be provided. Interestingly, the drug release rate monotonically decreased with increasing Dynasan 120 content, except for implants containing about 20-25% Precirol, which exhibited surprisingly high release rates. This could be attributed to the incomplete miscibility of the two lipids at these blend ratios: DSC thermograms showed phase separation in these systems. This is likely to cause differences in the implants' microstructure, which determines the mobility of water and dissolved drug as well as the mechanical stability of the systems. Purely diffusion controlled drug release was only observed at Precirol ATO 5 contents around 5-10%. In all other cases, limited drug solubility effects or matrix former erosion are also expected to play a major role. Thus, lipid:lipid blends are very interesting matrix formers in controlled release implants. However, care must be taken with respect to the mutual miscibility of the compounds: in case of phase separation, surprisingly high drug release rates might be observed.

  4. Stimuli-Responsive Materials for Controlled Release Applications

    KAUST Repository

    Li, Song

    2015-04-01

    The controlled release of therapeutics has been one of the major challenges for scientists and engineers during the past three decades. To address this outstanding problem, the design and fabrication of stimuli-responsive materials are pursued to guarantee the controlled release of cargo at a specific time and with an accurate amount. Upon applying different stimuli such as light, magnetic field, heat, pH change, enzymes or redox, functional materials change their physicochemical properties through physical transformation or chemical reactions, allowing the release of payload agents on demand. This dissertation studied three stimuli-responsive membrane systems for controlled release from films of macro sizes to microcapsules of nano sizes. The first membrane system is a polymeric composite film which can decrease and sustain diffusion upon light irradiation. The photo-response of membranes is based on the photoreaction of cinnamic derivatives. The second one is composite membrane which can improve diffusion upon heating. The thermo-response of membranes comes from the volume phase transition ability of hydrogels. The third one is microcapsule which can release encapsulated agents upon light irradiation. The photo-response of capsules results from the photoreaction of nitrobenzyl derivatives. The study on these membrane systems reveals that stimuli-responsive release can be achieved by utilizing different functional materials on either macro or micro level. Based on the abundant family of smart materials, designing and fabricating stimuli-responsive systems shall lead to various advanced release processes on demand for biomedical applications.

  5. DESIGN AND OPTIMIZATION OF CONTROLLED RELEASE OCULAR INSERTS OF DORZOLAMIDE HYDROCHLORIDE AND TIMOLOL MALEATE FOR TREATMENT OF GLAUCOMA

    Directory of Open Access Journals (Sweden)

    K.M. Manjunatha et al

    2012-10-01

    Full Text Available Goal of the present investigation was to formulate ocular inserts of dorzolamide hydrochloride and timolol maleate for the treatment of glaucoma. Ocular inserts of dorzolamide hydrochloride and timolol maleate were prepared using different polymers ethylcellulose, Eudragit RL 100, and Eudragit RS100 by solvent casting method with an objective to increasing the contact time, achieving controlled release, reducing in frequency of administration, and improving therapeutic efficacy. The drug-excipients interaction was studied by Fourier transform infrared spectroscopy (FTIR studies. Prepared ocular inserts were evaluated for their physicochemical properties such as uniformity of thickness, weight uniformity, tensile strength, percentage elongation, drug content, moisture loss, moisture absorption. The in vitro diffusion of drug from the inserts was studied using the classical biochemical donor - receptor compartment model fabricated in the laboratory and the formulation that showed better release profile was subjected to in vivo studies on albino-rabbits. Ocular irritation study was performed using healthy albino rabbits and confirmed that there was no irritation in the rabbit eyes. All the inserts were found to be uniform thickness and uniform weight. The inserts possessed good tensile strength and percentage elongation. All the formulations followed a first order release pattern. Optimized formulation RSRL3 showed high correlation coefficient (R = 0.996 & 0.995 respectively for dorzolamide HCl & timolol maleate between in vitro and in vivo release. Stability study was carried out on RSRL3 formulation and showed no significant changes in the drug content as well as physical characteristics of the film.

  6. Controlled release of tocopherols from polymer blend films

    Science.gov (United States)

    Obinata, Noe

    Controlled release packaging has great potential to increase storage stability of foods by releasing active compounds into foods continuously over time. However, a major limitation in development of this technology is the inability to control the release and provide rates useful for long term storage of foods. Better understanding of the factors affecting active compound release is needed to overcome this limitation. The objective of this research was to investigate the relationship between polymer composition, polymer processing method, polymer morphology, and release properties of active compounds, and to provide proof of principle that compound release is controlled by film morphology. A natural antioxidant, tocopherol was used as a model active compound because it is natural, effective, heat stable, and soluble in most packaging polymers. Polymer blend films were produced from combination of linear low density polyethylene (LLDPE) and high density polyethylene (HDPE), polypropylene (PP), or polystyrene (PS) with 3000 ppm mixed tocopherols using conventional blending method and innovative blending method, smart blending with a novel mixer using chaotic advection. Film morphologies were visualized with scanning electron microscopy (SEM). Release of tocopherols into 95% ethanol as a food simulant was measured by UV/Visible spectrophotometry or HPLC, and diffusivity of tocopherols in the polymers was estimated from this data. Polymer composition (blend proportions) and processing methods have major effects on film morphology. Four different types of morphologies, dispersed, co-continuous, fiber, and multilayer structures were developed by either conventional extrusion or smart blending. With smart blending of fixed polymer compositions, different morphologies were progressively developed with fixed polymer composition as the number of rod rotations increased, providing a way to separate effects of polymer composition and morphology. The different morphologies

  7. Controlled release of curcumin from poly(HEMA-MAPA) membrane.

    Science.gov (United States)

    Caka, Müşerref; Türkcan, Ceren; Aktaş Uygun, Deniz; Uygun, Murat; Akgöl, Sinan; Denizli, Adil

    2017-05-01

    In this work, poly(HEMA-MAPA) membranes were prepared by UV-polymerization technique. These membranes were characterized by SEM, FTIR, and swelling studies. Synthesized membranes had high porous structure. These membranes were used for controlled release of curcumin which is already used as folk remedy and used as drug for some certain diseases and cancers. Curcumin release was investigated for various pHs and temperatures. Optimum drug release yield was found to be as 70% at pH 7.4 and 37 °C within 2 h period. Time-depended release of curcumin was also investigated and its slow release from the membrane demonstrated within 48 h.

  8. 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.

  9. Optimization of matrix tablets controlled drug release using Elman dynamic neural networks and decision trees.

    Science.gov (United States)

    Petrović, Jelena; Ibrić, Svetlana; Betz, Gabriele; Đurić, Zorica

    2012-05-30

    The main objective of the study was to develop artificial intelligence methods for optimization of drug release from matrix tablets regardless of the matrix type. Static and dynamic artificial neural networks of the same topology were developed to model dissolution profiles of different matrix tablets types (hydrophilic/lipid) using formulation composition, compression force used for tableting and tablets porosity and tensile strength as input data. Potential application of decision trees in discovering knowledge from experimental data was also investigated. Polyethylene oxide polymer and glyceryl palmitostearate were used as matrix forming materials for hydrophilic and lipid matrix tablets, respectively whereas selected model drugs were diclofenac sodium and caffeine. Matrix tablets were prepared by direct compression method and tested for in vitro dissolution profiles. Optimization of static and dynamic neural networks used for modeling of drug release was performed using Monte Carlo simulations or genetic algorithms optimizer. Decision trees were constructed following discretization of data. Calculated difference (f(1)) and similarity (f(2)) factors for predicted and experimentally obtained dissolution profiles of test matrix tablets formulations indicate that Elman dynamic neural networks as well as decision trees are capable of accurate predictions of both hydrophilic and lipid matrix tablets dissolution profiles. Elman neural networks were compared to most frequently used static network, Multi-layered perceptron, and superiority of Elman networks have been demonstrated. Developed methods allow simple, yet very precise way of drug release predictions for both hydrophilic and lipid matrix tablets having controlled drug release.

  10. Core-in-cup tablet design of metoprolol succinate and its evaluation for controlled release.

    Science.gov (United States)

    Nagaraju, Ravouru; Meera, Durgumahanthi Sai; Kaza, Rajesh; Arvind, Vakati Venkata; Venkateswarlu, Vobalaboina

    2009-12-01

    The core-in-cup matrix tablets of Metoprolol succinate were prepared by wet granulation technique. Of all the investigated formulations, the optimized formulation of MS-09 followed zero-order kinetics of drug release. Trail on MS-09 was formulated using 7.5% hydrogenated castor-oil (HCO) and 4% of hydroxyl propyl methylcellulose (HPMC K15M) with an objective to achieve a linear release profile for 24 h. There is no initial burst release, with 16.17% of drug released during the first hour and release was extended up to 24 hrs. Study of drug release kinetics was performed by application of dissolution data to various kinetic equations like zero-order; first order, Higuchi and Korsmeyer-Peppas, from R(2) value (0.9975) it was concluded that the drug release followed zero order kinetics with both erosion and diffusion as the release mechanisms.

  11. Nutrients Release from a Novel Gel-Based Slow/Controlled Release Fertilizer

    Directory of Open Access Journals (Sweden)

    H. Ding

    2016-01-01

    Full Text Available A novel gel-based slow/controlled release fertilizer (G-CRF was developed, which was produced by combining various natural, seminatural, and/or synthetic organic macromolecule materials and natural inorganic mineral with conventional NPK fertilizers. Its nutrient release characteristics were studied to compare with conventional fertilizers through the soil column leaching method. The influences of soil factors, including temperature, pH, water, and nutrient contents in the G-CRF on nutrient release, were also investigated through soil-water incubation method. These results indicated that the G-CRF had better effect on controlling release of N, P, and K nutrients, and the effect was more efficient when soil-water content was lower than 45% (w/w, temperature was below 35°C, and soil pH was in the range from weak acid to neutral. In addition, considering the effect of controlling nutrient release and cost of the materials in the G-CRF, it is recommended that the most feasible NPK nutrient contents in the G-CRF ranged from 30 to 35%.

  12. Magnetic molecularly imprinted polymer for aspirin recognition and controlled release

    Science.gov (United States)

    Kan, Xianwen; Geng, Zhirong; Zhao, Yao; Wang, Zhilin; Zhu, Jun-Jie

    2009-04-01

    Core-shell structural magnetic molecularly imprinted polymers (magnetic MIPs) with combined properties of molecular recognition and controlled release were prepared and characterized. Magnetic MIPs were synthesized by the co-polymerization of methacrylic acid (MAA) and trimethylolpropane trimethacrylate (TRIM) around aspirin (ASP) at the surface of double-bond-functionalized Fe3O4 nanoparticles in chloroform. The obtained spherical magnetic MIPs with diameters of about 500 nm had obvious superparamagnetism and could be separated quickly by an external magnetic field. Binding experiments were carried out to evaluate the properties of magnetic MIPs and magnetic non-molecularly imprinted polymers (magnetic NIPs). The results demonstrated that the magnetic MIPs had high adsorption capacity and selectivity to ASP. Moreover, release profiles and release rate of ASP from the ASP-loaded magnetic MIPs indicated that the magnetic MIPs also had potential applications in drug controlled release.

  13. Magnetic molecularly imprinted polymer for aspirin recognition and controlled release

    Energy Technology Data Exchange (ETDEWEB)

    Kan Xianwen; Geng Zhirong; Zhao Yao; Wang Zhilin; Zhu Junjie [State Key Laboratory of Coordination Chemistry, MOE Key Lab of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, 22 Hankou Road, Nanjing 210093 (China)], E-mail: wangzl@nju.edu.cn, E-mail: jjzhu@nju.edu.cn

    2009-04-22

    Core-shell structural magnetic molecularly imprinted polymers (magnetic MIPs) with combined properties of molecular recognition and controlled release were prepared and characterized. Magnetic MIPs were synthesized by the co-polymerization of methacrylic acid (MAA) and trimethylolpropane trimethacrylate (TRIM) around aspirin (ASP) at the surface of double-bond-functionalized Fe{sub 3}O{sub 4} nanoparticles in chloroform. The obtained spherical magnetic MIPs with diameters of about 500 nm had obvious superparamagnetism and could be separated quickly by an external magnetic field. Binding experiments were carried out to evaluate the properties of magnetic MIPs and magnetic non-molecularly imprinted polymers (magnetic NIPs). The results demonstrated that the magnetic MIPs had high adsorption capacity and selectivity to ASP. Moreover, release profiles and release rate of ASP from the ASP-loaded magnetic MIPs indicated that the magnetic MIPs also had potential applications in drug controlled release.

  14. 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

  15. FERLENT - a controlled release fertilizer produced from a polymer material

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2011-07-01

    The possibility to use release controlled fertilizers in the agriculture of the tropical countries is more important than in the agriculture of the countries of the template regions. In this context, this work purpose the development of a new Fertilizer of Controlled Release named FERLENT, which was obtained starting from a polymeric material, under controlled conditions which allowed to corroborate the adjustment of the synthesis parameters under the modulate of nutrients liberation. It was characterized by, Scanning Microscopy Electron (SEM), Thermogravimetric analysis (TGA), Nuclear Magnetic Resonance (NMR) and infrared spectroscopy (FTIR). (author)

  16. Design and Comparative Evaluation of In-vitro Drug Release, Pharmacokinetics and Gamma Scintigraphic Analysis of Controlled Release Tablets Using Novel pH Sensitive Starch and Modified Starch- acrylate Graft Copolymer Matrices

    Science.gov (United States)

    Kumar, Pankaj; Ganure, Ashok Laxmanrao; Subudhi, Bharat Bhushan; Shukla, Shubhanjali

    2015-01-01

    The present investigation deals with the development of controlled release tablets of salbutamol sulphate using graft copolymers (St-g-PMMA and Ast-g-PMMA) of starch and acetylated starch. Drug excipient compatibility was spectroscopically analyzed via FT-IR, which confirmed no interaction between drug and other excipients. Formulations were evaluated for physical characteristics like hardness, friability, weight variations, drug release and drug content analysis which satisfies all the pharmacopoeial requirement of tablet dosage form. Release rate of a model drug from formulated matrix tablets were studied at two different pH namely 1.2 and 6.8, spectrophotometrically. Drug release from the tablets of graft copolymer matrices is profoundly pH-dependent and showed a reduced release rate under acidic conditions as compared to the alkaline conditions. Study of release mechanism by Korsmeyer’s model with n values between 0.61-0.67, proved that release was governed by both diffusion and erosion. In comparison to starch and acetylated starch matrix formulations, pharmacokinetic parameters of graft copolymers matrix formulations showed a significant decrease in Cmax with an increase in tmax, indicating the effect of dosage form would last for longer duration. The gastro intestinal transit behavior of the formulation was determined by gamma scintigraphy, using 99mTc as a marker in healthy rabbits. The amount of radioactive tracer released from the labelled tablets was minimal when the tablets were in the stomach, whereas it increased as tablets reached to intestine. Thus, in-vitro and in-vivo drug release studies of starch-acrylate graft copolymers proved their controlled release behavior with preferential delivery into alkaline pH environment. PMID:26330856

  17. Controlled drug-release system based on pH-sensitive chloride-triggerable liposomes.

    Science.gov (United States)

    Wehunt, Mark P; Winschel, Christine A; Khan, Ali K; Guo, Tai L; Abdrakhmanova, Galya R; Sidorov, Vladimir

    2013-03-01

    New pH-sensitive lipids were synthesized and utilized in formulations of liposomes suitable for controlled drug release. These liposomes contain various amounts of NaCl in the internal aqueous compartments. The release of the drug model is triggered by an application of HCl cotransporter and exogenous physiologically relevant NaCl solution. HCl cotransporter allows an uptake of HCl by liposomes to the extent of their being proportional to the transmembrane Cl(-) gradient. Therefore, each set of liposomes undergoes internal acidification, which, ultimately, leads to the hydrolysis of the pH-sensitive lipids and content release at the desired time. The developed system releases the drug model in a stepwise fashion, with the release stages separated by periods of low activity. These liposomes were found to be insensitive to physiological concentrations of human serum albumin and to be nontoxic to cells at concentrations exceeding pharmacological relevance. These results render this new drug-release model potentially suitable for in vivo applications.

  18. Chemical analysis of substrates with controlled release fertilizer

    NARCIS (Netherlands)

    Kreij, de C.

    2004-01-01

    Water-soluble fertilizer added to media containing controlled release fertilizer cannot be analysed with the 1:1.5 volume water extract, because the latter increases the element content in the extract. During storage and stirring or mixing the substrate with the extractant, part of the controlled re

  19. Controlled release fertilizer improves quality of container longleaf pine seedlings

    Science.gov (United States)

    R. Kasten Dumroese; Jeff Parkhurst; James P. Barnett

    2005-01-01

    In an operational trial, increasing the amount of nitrogen (N) applied to container longleaf pine seedlings by incorporating controlled release fertilizer (CRF) into the media improved seedling growth and quality. Compared with control seedlings that received 40 mg N, seedlings receiving 66 mg N through CRF supplemented with liquid fertilizer had needles that were 4 in...

  20. Chemical analysis of substrates with controlled release fertilizer

    NARCIS (Netherlands)

    Kreij, de C.

    2004-01-01

    Water-soluble fertilizer added to media containing controlled release fertilizer cannot be analysed with the 1:1.5 volume water extract, because the latter increases the element content in the extract. During storage and stirring or mixing the substrate with the extractant, part of the controlled re

  1. [Controlled release hydromorphone for visceral, somatic and neuropathic pain].

    Science.gov (United States)

    Alon, E; Cachin, C

    2010-03-03

    The aim of this multicentre, longitudinal investigation was to document the efficacy and tolerability profiles of controlled release hydromorphone in patients with heavy visceral, somatic or neuropathic pain under practical conditions. To this end, a prospective observational study was conducted in 57 centres in Switzerland, on a total of 196 patients. After an average of 43 days of treatment with controlled release hydromorphone, the intensity of momentary pain dropped by 46.5% and that of maximum pain dropped by 41.3%, with the efficacy of the treatment being most pronounced with visceral and somatic pain. At the same time, the prevalence of sleep disorders as a result of pain decreased from initially 86.7% to 21.0%. Controlled release hydromorphone was excellently tolerated in this group of elderly (average age 70.6 years), multimorbid pain patients receiving various medical treatments (average of 2.4 drugs in addition to pain medication), even in the voluntary long-term extension study of up to 96 days. No medical interactions were reported. Six and thirteen weeks after introducing the treatment, 89.8% and 85.2%, respectively, were still taking controlled release hydromorphone. Controlled release hydromorphone is a recommendable option for practical treatment of heavy and extremely heavy pain of various genesis.

  2. 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.

  3. Antimicrobial beeswax coated polylactide films with silver control release capacity.

    Science.gov (United States)

    Martínez-Abad, Antonio; Lagarón, Jose Maria; Ocio, María Jose

    2014-03-17

    Although the application of silver based antimicrobial systems is a widespread technology, its implementation in areas such as food packaging is still challenging. The present paper describes the fabrication of poly(lactic acid) (PLA) coated with beeswax with controlled release properties for sustained antimicrobial performance. Release of silver ions from the polymers was monitored voltammetrically under various conditions (surface contact, immersion in various liquid media and at different pH values) throughout at least 7days. A higher release was noted with decreasing pH while surface release was much slower than the release when immersed in liquid medium. While uncoated films demonstrated a high burst release which in some instances implied surpassing some current migration restrictions (beeswax layer allowed a sustained release of the antimicrobial compound. Increasing the thickness of the beeswax layer resulted in an increase in the water barrier properties of the films while reducing the relatively constant values of sustained release. Antimicrobial performance was correlated with the release of silver ions, indicating threshold concentrations for biocide action of <6μg/L and 9-14μg/L for surface contact and in liquid media, respectively. Either by surface contact or by immersion in growth medium or vegetable soup, the coated films displayed a strong bactericidal effect against Salmonella enterica. The application of this functional barrier thus offers the possibility of tuning the release profiles of the films to suit a specific application and puts forth the possible suitability of these materials for food packaging or other migration sensitive applications.

  4. 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.

  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. Economic model predictive control theory, formulations and chemical process applications

    CERN Document Server

    Ellis, Matthew; Christofides, Panagiotis D

    2017-01-01

    This book presents general methods for the design of economic model predictive control (EMPC) systems for broad classes of nonlinear systems that address key theoretical and practical considerations including recursive feasibility, closed-loop stability, closed-loop performance, and computational efficiency. Specifically, the book proposes: Lyapunov-based EMPC methods for nonlinear systems; two-tier EMPC architectures that are highly computationally efficient; and EMPC schemes handling explicitly uncertainty, time-varying cost functions, time-delays and multiple-time-scale dynamics. The proposed methods employ a variety of tools ranging from nonlinear systems analysis, through Lyapunov-based control techniques to nonlinear dynamic optimization. The applicability and performance of the proposed methods are demonstrated through a number of chemical process examples. The book presents state-of-the-art methods for the design of economic model predictive control systems for chemical processes. In addition to being...

  7. Design and evaluation of controlled release mucoadhesive microspheres of amoxicillin for anti Helicobacter pylori therapy

    Directory of Open Access Journals (Sweden)

    N Venkateswaramurthy

    2011-01-01

    Full Text Available The aim of this study was to develop controlled release mucoadhesive microspheres of amoxicillin trihydrate for the treatment of peptic ulcer disease caused by Helicobacter pylori (H. pylori. Microspheres were prepared by solvent evaporation technique using carbopol 974P, hydroxypropyl methyl cellulose K4M (HPMC K4M and Eudragit RS 100. The prepared microspheres were subjected to evaluation for particle size, incorporation efficiency, in vitro mucoadhesion and in vitro drug release characteristics. Absence of drug-polymer interaction was confirmed using differential scanning calorimetry analysis and fourier transform infrared spectrophotometry. The prepared microspheres showed a strong mucoadhesive property. The polymer concentration influenced the in vitro drug release significantly in 0.1N HCl. The particle sizes of systems ranged between 123±8.35 μm and 524±11.54 μm. Percent drug entrapment and release profiles of amoxicillin trihydrate in 0.1 N HCl were determined using high-performance liquid chromatography. The percentage drug entrapment and percentage yield of formulations were about 56.71±1.66% to 88.32±0.65% and 39.20±1.62% to 92.40±1.32%, respectively. The stability of the drugs was assessed in 0.1 N HCl. The results further substantiated that mucoadhesive microspheres improved the gastric stability of amoxicillin trihydrate (due to entrapment within the microsphere. From the above results, it was concluded that the mucoadhesive microspheres of amoxicillin trihydrate has feasibility for eradicating H. pylori from the stomach more effectively because of the prolonged gastrointestinal residence time and controlled release of drug from the formulation.

  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. Control-Theoretic Formulation of Operating Systems Resource Management Policies.

    Science.gov (United States)

    1978-05-01

    algorithm) controls the transfer of pages from virtual memory (disk or drum) to primary memory, and so on. - - - -- i nt roductlocn Pige 1-3 log in Rqet...the primary memory. Til : situation is called " pige fault". On a page fault, the demanded page is brought in to the core. Space for the incoming page

  10. Comparative evaluation of polymersome versus micelle structures as vehicles for the controlled release of drugs

    Energy Technology Data Exchange (ETDEWEB)

    Alibolandi, Mona [Mashhad University of Medical Sciences, Biotechnology Research Center, School of Pharmacy (Iran, Islamic Republic of); Ramezani, Mohammad; Abnous, Khalil [Mashhad University of Medical Sciences, Pharmaceutical Research Center, School of Pharmacy (Iran, Islamic Republic of); Sadeghi, Fatemeh, E-mail: sadeghif@mums.ac.ir [Mashhad University of Medical Sciences, Targeted Drug Delivery Research Center, School of Pharmacy (Iran, Islamic Republic of); Hadizadeh, Farzin, E-mail: hadizadehf@mums.ac.ir [Mashhad University of Medical Sciences, Biotechnology Research Center, School of Pharmacy (Iran, Islamic Republic of)

    2015-02-15

    Di-block copolymers composed of two biocompatible polymers, poly(ethylene glycol) and poly(d,l-lactide), were synthesized by ring-opening polymerization for the preparation of doxorubicin-loaded self-assembled nanostructures, including polymeric vesicles (polymersomes) and micelles. The capability and stability of the nanostructures prepared for the controlled release of DOX are discussed in this paper. The in vitro drug release at 37 °C was evaluated up to 6 days at pH 7.4 and 5.5 and in the presence of 50 % FBS. The cellular uptake and cytotoxicity effect of both formulations were also evaluated in the MCF-7 cell line. The SEM and AFM images confirmed the hollow spherical structure of the polymersomes and the solid round structures of the micelles. The TEM results also revealed the uniformity in size and shape of the drug-loaded micelle and polymersome nanostructures. The DOX-loaded micelles and polymersomes presented efficient anticancer performance, as verified by flow cytometry and MTT assay tests. The most important finding of this study is that the prepared nanopolymersomes presented significant increases in the doxorubicin encapsulation efficiency and the stability of the formulation in comparison with the micelle formulation. In vitro studies revealed that polymersomes may be stable in the blood circulation and meet the requirements for an effective drug delivery system.

  11. Controlled release ibuprofen-poloxamer gel for epidural use - A pharmacokinetic study using microdialysis in pigs.

    Science.gov (United States)

    Paavola, Anne; Bernards, Christopher M; Rosenberg, Per H

    2016-11-01

    In order to avoid the risks of sideeffects of epidural local anesthetics and opioids, the use of nonsteroidal anti-inflammatory drugs (NSAIDs) epidurally would be an interesting option of analgesic therapy. The fairly short duration of action of spinally administered NSAIDs, e.g., ibuprofen, may be prolonged by using controlled release poloxamer gel formulation. Using a microdialysis technique we studied the epidural and intrathecal pharmacokinetics of ibuprofen after its epidural administration as a poloxamer 407 formulation or a solution formulation. In addition, plasma ibuprofen concentrations were analyzed from central venous blood samples. Ibuprofen concentrations in the epidural space were significantly higher and longer lasting after the epidural gel injection compared with the epidural solution injection. The epidural AUC of ibuprofen was over threefold greater after epidural ibuprofen gel injection compared with the ibuprofen solution injection (pgel was very low. The in situ forming poloxamer gel acted as a reservoir allowing targeted ibuprofen release at the epidural injection site and restricted ibuprofen molecules to a smaller spinal area. Ibuprofen diffusion from the epidural space to the intrathecal space was steady and prolonged. These results demonstrate that the use of epidurally injectable poloxamer gel can increase and prolong ibuprofen delivery from epidural space to the CSF enhancing thus ibuprofen entry into the central neuroaxis for spinal analgesia. Further toxicological and dose-finding studies are justified.

  12. Control Efficacy of Serenade Formulation against Rhizoctonia and Pythium Damping-off Diseases

    Directory of Open Access Journals (Sweden)

    Eun Ju Jo

    2014-09-01

    Full Text Available Damping-off, caused by Rhizoctonia solani and Pythium ultimum, is a very important plant disease and affects seeds and seedlings of many plant species worldwide. To investigate control efficacy of Serenade formulation (1.34%, SC against Rhizoctonia and Pythium damping-off diseases, seeds of chili pepper and cucumber were sown in soils inoculated with R. solani and P. ultimum and Serenade formulation was applied by soil-drenching with 9-, 19-, and 39-fold dilutions. Control values of Serenade formulation on Rhizoctonia damping-off of chili pepper was 58% and 29% for 9- and 19-fold dilutions, respectively. In the case of cucumber Rhizoctonia damping-off, Serenade treatments showed similar control efficacy with damping-off of chili pepper. On the other hand, control efficacy of Serenade formulation on Pythium damping-off of cucumber was less than control effects on Rhizoctonia damping-off. Only Pythium damping-off of chili pepper treated with 9-fold dilution Serenade was statistically different with untreated control. This result suggest that Serenade formulation could be effectively used for controlling Rhizoctonia and Pythium damping-off diseases.

  13. Press-coating of immediate release powders onto coated controlled release tablets with adhesives.

    Science.gov (United States)

    Waterman, Kenneth C; Fergione, Michael B

    2003-05-20

    A novel adhesive coating was developed that allows even small quantities of immediate-release (IR) powders to be press-coated onto controlled-release (CR), coated dosage forms without damaging the CR coating. The process was exemplified using a pseudoephedrine osmotic tablet (asymmetric membrane technology, AMT) where a powder weighing less than 25% of the core was pressed onto the osmotic tablet providing a final combination tablet with low friability. The dosage form with the adhesive plus the press-coated powder showed comparable sustained drug release rates to the untreated dosage form after an initial 2-h lag. The adhesive layer consisted of an approximately 100- microm coating of Eudragit RL, polyethylene glycol (PEG) and triethyl citrate (TEC) at a ratio of 5:3:1.2. This coating provides a practical balance between handleability before press-coating and good adhesion.

  14. Emulsified lipids: formulation and control of end-use properties

    Directory of Open Access Journals (Sweden)

    Leal-Calderon Fernando

    2012-03-01

    Full Text Available In many practical applications including foods, cosmetics, pharmaceuticals, etc., lipids are emulsified in an aqueous phase in the presence of surface-active molecules and other additives like thickening/gelling agents. Once fabricated, the emulsions may exhibit all kinds of rheological behaviors from viscous fluid to elastic pastes, and transitions: reversible phase transitions as a result of droplet interactions that may be modified to a large extent, and irreversible transitions that generally involve their destruction. Besides the predominance of empiricism in controlling most of the end-use properties, the scientific background of emulsions is progressing. In this paper we aim to review some advances concerning the control of the structure, the texture (rheological properties and the ageing of emulsions.

  15. 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).

  16. Clean Photothermal Heating and Controlled Release from Near-Infrared Dye Doped Nanoparticles without Oxygen Photosensitization.

    Science.gov (United States)

    Guha, Samit; Shaw, Scott K; Spence, Graeme T; Roland, Felicia M; Smith, Bradley D

    2015-07-21

    The photothermal heating and release properties of biocompatible organic nanoparticles, doped with a near-infrared croconaine (Croc) dye, were compared with analogous nanoparticles doped with the common near-infrared dyes ICG and IR780. Separate formulations of lipid-polymer hybrid nanoparticles and liposomes, each containing Croc dye, absorbed strongly at 808 nm and generated clean laser-induced heating (no production of (1)O2 and no photobleaching of the dye). In contrast, laser-induced heating of nanoparticles containing ICG or IR780 produced reactive (1)O2, leading to bleaching of the dye and also decomposition of coencapsulated payload such as the drug doxorubicin. Croc dye was especially useful as a photothermal agent for laser-controlled release of chemically sensitive payload from nanoparticles. Solution state experiments demonstrated repetitive fractional release of water-soluble fluorescent dye from the interior of thermosensitive liposomes. Additional experiments used a focused laser beam to control leakage from immobilized liposomes with very high spatial and temporal precision. The results indicate that fractional photothermal leakage from nanoparticles doped with Croc dye is a promising method for a range of controlled release applications.

  17. AN IN-VITRO STUDY FOR MUCOADHESION AND CONTROL RELEASE PROPERTIES OF GUAR GUM AND CHITOSAN IN ITRACONAZOLE MUCOADHESIVE TABLETS

    Directory of Open Access Journals (Sweden)

    A. A. Shaikh*, Y. D. Pawar and S. T. Kumbhar

    2012-05-01

    Full Text Available This study describes the effect of Guar gum and chitosan on formulation of mucoadhesive drug delivery system of itraconazole. Mucoadhesive strength, Drug content, Hardness, Friability, Weight variation, Moisture content and accelerated stability studies were performed to study the effect of polymers on prepared mucoadhesive tablets. Results of the present study clarified the potential of guar gum and chitosan in mucoadhesion and control release of itraconazole tablets. Both polymers i.e. Chitosan and guar gum were helpful for controlling the drug release in better way when used in proper combinations. When result of mucoadhesion was checked guar gum gives more mucoadhesive strength to the prepared tablets as compared to chitosan. Accelerated stability studies were performed on prepared formulations, results indicates that the formulations were stable that mince excipients used in the formulations were stable and are not causing major changes in drug release pattern after a period of 6 months. From above mentioned work it can be concluded that combination of Chitosan and guar gum is better and effective approach to have controlled mucoadhesive drug delivery system of Itraconazole.

  18. Development and in vitro/in vivo evaluation of controlled release provesicles of a nateglinide–maltodextrin complex

    Directory of Open Access Journals (Sweden)

    Ranjan Ku. Sahoo

    2014-10-01

    Full Text Available The aim of this study was to characterize the provesicle formulation of nateglinide (NTG to facilitate the development of a novel controlled release system of NTG with improved efficacy and oral bioavailability compared to the currently marketed NTG formulation (Glinate™ 60. NTG provesicles were prepared by a slurry method using the non-ionic surfactant, Span 60 (SP, and cholesterol (CH as vesicle forming agents and maltodextrin as a coated carrier. Multilamellar niosomes with narrow size distribution were shown to be successfully prepared by means of dynamic laser scattering (DLS and field emission scanning electron microscopy (FESEM. The absence of drug-excipient interactions was confirmed by Fourier transform infrared spectroscopy (FT-IR, differential scanning calorimetry (DSC and X-ray diffraction (XRD studies. In vitro release of NTG in different dissolution media was improved compared to pure drug. A goat intestinal permeation study revealed that the provesicular formulation (F4 with an SP:CH ratio of 5:5 gave higher cumulative amount of drug permeated at 48 h compared to Glinate™ 60 and control. A pharmacodynamic study in streptozotocin-induced diabetic rats confirmed that formulation F4 significantly (P<0.05 reduced blood glucose levels in comparison to Glinate 60. Overall the results show that controlled release NTG provesicles offer a useful and promising oral delivery system for the treatment of type II diabetes.

  19. Development and optimization of novel controlled-release pioglitazone provesicular powders using 3² factorial design.

    Science.gov (United States)

    Shukr, Marwa H; Eltablawy, Nadia A

    2015-02-01

    This work aimed at studying a novel controlled drug delivery proniosomal formulation of pioglitazone for treatment of diabetes type-2. The effects of independent variables like type of surfactant and ratio of surfactants/cholesterol were studied using 3(2) factorial design. The provesicular powders were characterized regarding their encapsulation efficiency, vesicle size, morphology, and in vitro drug release. The revealed optimal provesicular powder was exposed to stability testing and in vivo performance evaluation. Results showed that F6 was selected as the optimal formulation, and its in vivo hypoglycemic effect on normal healthy and STZ-induced diabetic albino rats was investigated. F6 proniosomal formulation exhibited a significantly higher % decrease (56.18 % for STZ-induced diabetic albino rats) of blood glucose level (BGL) than Actos® (32. % for STZ-induced diabetic albino rats). Higher % decrease of BGL with longer t max and lower AUC0-24 confirms the development of a successful proniosomal pioglitazone formulation.

  20. Evaluation of Direct Collocation Optimal Control Problem Formulations for Solving the Muscle Redundancy Problem.

    Science.gov (United States)

    De Groote, Friedl; Kinney, Allison L; Rao, Anil V; Fregly, Benjamin J

    2016-10-01

    Estimation of muscle forces during motion involves solving an indeterminate problem (more unknown muscle forces than joint moment constraints), frequently via optimization methods. When the dynamics of muscle activation and contraction are modeled for consistency with muscle physiology, the resulting optimization problem is dynamic and challenging to solve. This study sought to identify a robust and computationally efficient formulation for solving these dynamic optimization problems using direct collocation optimal control methods. Four problem formulations were investigated for walking based on both a two and three dimensional model. Formulations differed in the use of either an explicit or implicit representation of contraction dynamics with either muscle length or tendon force as a state variable. The implicit representations introduced additional controls defined as the time derivatives of the states, allowing the nonlinear equations describing contraction dynamics to be imposed as algebraic path constraints, simplifying their evaluation. Problem formulation affected computational speed and robustness to the initial guess. The formulation that used explicit contraction dynamics with muscle length as a state failed to converge in most cases. In contrast, the two formulations that used implicit contraction dynamics converged to an optimal solution in all cases for all initial guesses, with tendon force as a state generally being the fastest. Future work should focus on comparing the present approach to other approaches for computing muscle forces. The present approach lacks some of the major limitations of established methods such as static optimization and computed muscle control while remaining computationally efficient.

  1. LQR Control of Thin Shell Dynamics: Formulation and Numerical Implementation

    Science.gov (United States)

    delRosario, R. C. H.; Smith, R. C.

    1997-01-01

    A PDE-based feedback control method for thin cylindrical shells with surface-mounted piezoceramic actuators is presented. Donnell-Mushtari equations modified to incorporate both passive and active piezoceramic patch contributions are used to model the system dynamics. The well-posedness of this model and the associated LQR problem with an unbounded input operator are established through analytic semigroup theory. The model is discretized using a Galerkin expansion with basis functions constructed from Fourier polynomials tensored with cubic splines, and convergence criteria for the associated approximate LQR problem are established. The effectiveness of the method for attenuating the coupled longitudinal, circumferential and transverse shell displacements is illustrated through a set of numerical examples.

  2. A dynamical formulation for multiflexible controlled spacecraft simulation

    Science.gov (United States)

    Corrado, G.; Ravazzotti, M. T.

    1981-09-01

    The dynamic behavior of highly flexible, rotating spacecraft is described by a method which does not require any particular approximation and is not limited to any particular arrangement of the bodies constituting the system. The analytical technique is based on the formalism of the DISCOS computer program (Bodley, 1978), a powerful tool for the dynamic simulation of complex spacecraft. The state equations, described in a general format, are applicable to any complex spacecraft under any environmental load. The approach takes into account the distributed flexibility, the relative motion of the bodies, the automatic coupling of the momentum wheels, the system control laws, and their interaction with the structure. Synthesis and analysis of the linearized system are used to solve time and frequency equations. The required computing times for different program options are listed, along with the number of equations and the integration step size. A block diagram of the DISCOS package structure is given, showing the development from problem definition to simulation results.

  3. Automated drop-on-demand system with real-time gravimetric control for precise dosage formulation.

    Science.gov (United States)

    Sahay, A; Brown, M; Muzzio, F; Takhistov, Paul

    2013-04-01

    Many of the therapies for personalized medicine have few dosage options, and the successful translation of these therapies to the clinic is significantly dependent on the drug/formulation delivery platform. We have developed a lab-scale integrated system for microdosing of drug formulations with high accuracy and precision that is capable of feedback control. The designed modular drug dispensing system includes a microdispensing valve unit and is fully automated with a LabVIEW-controlled computer interface. The designed system is capable of dispensing drug droplets with volumes ranging from nanoliters to microliters with high accuracy (relative standard deviation gravimetric control.

  4. Controlled antiseptic release by alginate polymer films and beads.

    Science.gov (United States)

    Liakos, Ioannis; Rizzello, Loris; Bayer, Ilker S; Pompa, Pier Paolo; Cingolani, Roberto; Athanassiou, Athanassia

    2013-01-30

    Biodegradable polymeric materials based on blending aqueous dispersions of natural polymer sodium alginate (NaAlg) and povidone iodine (PVPI) complex, which allow controlled antiseptic release, are presented. The developed materials are either free standing NaAlg films or Ca(2+)-cross-linked alginate beads, which properly combined with PVPI demonstrate antibacterial and antifungal activity, suitable for therapeutic applications, such as wound dressing. Glycerol was used as the plasticizing agent. Film morphology was studied by optical and atomic force microscopy. It was found that PVPI complex forms well dispersed circular micro-domains within the NaAlg matrix. The beads were fabricated by drop-wise immersion of NaAlg/PVPI/glycerol solutions into aqueous calcium chloride solutions to form calcium alginate beads encapsulating PVPI solution (CaAlg/PVPI). Controlled release of PVPI was possible when the composite films and beads were brought into direct contact with water or with moist media. Bactericidal and fungicidal properties of the materials were tested against Escherichia coli bacteria and Candida albicans fungi. The results indicated very efficient antibacterial and antifungal activity within 48 h. Controlled release of PVPI into open wounds is highly desired in clinical applications to avoid toxic doses of iodine absorption by the wound. A wide variety of applications are envisioned such as external and internal wound dressings with controlled antiseptic release, hygienic and protective packaging films for medical devices, and polymer beads as water disinfectants.

  5. Biopolymers in controlled release devices for agricultural applications.

    Science.gov (United States)

    The use of biopolymers such as starch for agricultural applications including controlled release devices is growing due the environmental benefits. Recently, concerns have grown about the worldwide spread of parasitic mites (Varroa destructor) that infect colonies of honey bees (Apis mellifera L.). ...

  6. Using Randomized Controlled Trials to Evaluate Interventions for Releasing Prisoners

    Science.gov (United States)

    Pettus-Davis, Carrie; Howard, Matthew Owen; Dunnigan, Allison; Scheyett, Anna M.; Roberts-Lewis, Amelia

    2016-01-01

    Randomized controlled trials (RCTs) are rarely used to evaluate social and behavioral interventions designed for releasing prisoners. Objective: We use a pilot RCT of a social support intervention (Support Matters) as a case example to discuss obstacles and strategies for conducting RCT intervention evaluations that span prison and community…

  7. Composition for the controlled release of active compounds

    NARCIS (Netherlands)

    Hovens, I.A.P.; Jongboom, R.O.J.; Stuut, P.I.

    1999-01-01

    The invention provides a composition for the controlled release of one or more biologically active substances encapsulated in a degradable biopolymer matrix, consisting of a thermoplastic and/or partly crystalline inulin. A plasticiser such as glycerol, and an emulsifier may be present. The active s

  8. Rectal absorption of morphine from controlled release suppositories

    NARCIS (Netherlands)

    Moolenaar, Frits; Meyler, Pim; Frijlink, Erik; Jauw, Tjoe Hang; Visser, Jan; Proost, Johannes

    1995-01-01

    The absorption profiles and bioavailability of morphine in human volunteers (n = 13) were described after oral administration of MS Contin tablets and rectal administration of a newly developed controlled release suppository. By manipulating the viscosity of fatty suppository base an entirely

  9. Improvement of waste release control in French NPP

    Energy Technology Data Exchange (ETDEWEB)

    Samson, T.; Lucquin, E.; Dupin, M. [EDF/GDL (France); Florence, D. [EDF/GENV (France); Grisot, M. [EDF/CNPE Saint Laurent (France)

    2002-07-01

    The new waste release control in French NPP is more restrictive than the old one and needs heavy investment to bring plants to compliance with it. The great evolutions are a chemical follow up on more chemicals with a higher measurement frequency and with lower maximum concentrations and a specific measurement of carbon 14. Regarding radioactive releases, a new counting has been settled and activity of carbon 14 release is now measured and no longer calculated. The evolution of the French regulation leads to develop specific procedures and analytical techniques in chemistry and in radiochemistry (UV spectrometric methods, carbon 14 measurements,..) EDF NPP operators have launched a voluntarist process to reduce their releases since the beginning and before the evolution of the regulation. EDF priorities in terms of environment care lead henceforth to implement a global optimisation of the impact for a better control of releases. The new regulation will help EDF to reach its goals because it covers all the aspects in one administrative document: it is seen as a real simplification and a clarification towards public. In addition, this new regulation fits in with international practices which will allow an easier comparison of results between EDF and foreign NPP. These big environmental concerns lead EDF to create a national dedicated laboratory (LAMEN) in charge of developing specific measurement procedures to be implemented either by NPP or by sub-contractor laboratories. (authors)

  10. Multifunctional conducting fibres with electrically controlled release of ciprofloxacin.

    Science.gov (United States)

    Esrafilzadeh, Dorna; Razal, Joselito M; Moulton, Simon E; Stewart, Elise M; Wallace, Gordon G

    2013-08-10

    We hereby present a new method of producing coaxial conducting polymer fibres loaded with an antibiotic drug that can then be subsequently released (or sustained) in response to electrical stimulation. The method involves wet-spinning of poly(3,4-ethylenedioxythiophene) poly(styrenesulfonate) (PEDOT:PSS) fibre, which served as the inner core to the electropolymerised outer shell layer of polypyrrole (Ppy). Ciprofloxacin hydrochloride (Cipro) was selected as the model drug and as the dopant in the Ppy synthesis. The release of Cipro in phosphate buffered saline (PBS) from the fibres was controlled by switching the redox state of Ppy.Cipro layer. Released Cipro under passive and stimulated conditions were tested against Gram positive (Streptococcus pyogenes) and Gram negative (Escherichia coli) bacteria. Significant inhibition of bacterial growth was observed against both strains tested. These results confirm that Cipro retains antibacterial properties during fibre fabrication and electrochemically controlled release. In vitro cytotoxicity testing utilising the neural B35 cell line confirmed the cytocompatibility of the drug loaded conducting fibres. Electrical conductivity, cytocompatibility and tuning release profile from this flexible fibre can lead to promising bionic applications such as neuroprosthetics and localised drug delivery. Copyright © 2013 Elsevier B.V. All rights reserved.

  11. Controlled release of ethylene via polymeric films for food packaging

    Science.gov (United States)

    Pisano, Roberto; Bazzano, Marco; Capozzi, Luigi Carlo; Ferri, Ada; Sangermano, Marco

    2015-12-01

    In modern fruit supply chain a common method to trigger ripening is to keep fruits inside special chambers and initiate the ripening process through administration of ethylene. Ethylene is usually administered through cylinders with inadequate control of its final concentration in the chamber. The aim of this study is the development of a new technology to accurately regulate ethylene concentration in the atmosphere where fruits are preserved: a polymeric film, containing an inclusion complex of α-cyclodextrin with ethylene, was developed. The complex was prepared by molecular encapsulation which allows the entrapment of ethylene into the cavity of α-cyclodextrin. After encapsulation, ethylene can be gradually released from the inclusion complex and its release rate can be regulated by temperature and humidity. The inclusion complex was dispersed into a thin polymeric film produced by UV-curing. This method was used because is solvent-free and involves low operating temperature; both conditions are necessary to prevent rapid release of ethylene from the film. The polymeric films were characterized with respect to thermal behaviour, crystalline structure and kinetics of ethylene release, showing that can effectively control the release of ethylene within confined volume.

  12. Bioadhesive emulsions for control release of progesterone resistant to vaginal fluids clearance.

    Science.gov (United States)

    Campaña-Seoane, Maria; Peleteiro, Aaron; Laguna, Reyes; Otero-Espinar, Francisco J

    2014-12-30

    The aim of this study is to propose that mucoadhesive vaginal emulsions can be able to resist the clearance effect of vaginal fluid and to have an effective control release of progesterone. With this goal, silicon derivative, cyclomethicone pentamer, was selected as the bioadhesive and water resistant material. In order to obtain a system which is insensitive to the dilution of aqueous fluids, water in silicone (W/S) emulsions were prepared and different proportions of cyclomethicone as well as 8% or 15% w/w of progesterone were employed. The rheological, mechanical and mucoadhesive properties of emulsions were characterized and the drug release was measured for each formulation. Mucoadhesive behavior was determined and the influence of simulated vaginal fluid (SVF) at bioadhesion was assessed using three commercial mucoadhesive vaginal gels (Crinone(®), K-Y jelly(®) and Zidoval(®)) as the bioadhesive references. All assayed emulsions have good rheological and mechanical properties and their consistence and viscosity increase when the proportion of the internal phase increases. Related to mucoadhesion, in the absence of SVF, W/S emulsions showed similar bioadhesive levels like the commercial formulations. However, in the presence of SVF, W/S emulsions are able to keep their mucoadhesive properties while the marketed references drastically lose their consistency and adherence to the vaginal mucosa. Drug release profiles from W/S emulsion show that progesterone is released with pseudo-order zero kinetics and a constant release rate is maintained for at least two weeks. The results of the in vivo studies developed in rats show that after a single vaginal administration, bioadhesive W/S emulsions increase the uterine tissue progesterone levels in young and postmenopausal rats. Moreover in postmenopausal rats, they provide high uterine levels of progesterone compared to the bioadhesive-marketed gel used as a reference. Therefore, W/S emulsions have an interesting

  13. Oral controlled release drug delivery system and Characterization of oral tablets; A review

    Directory of Open Access Journals (Sweden)

    Muhammad Zaman

    2016-01-01

    Full Text Available Oral route of drug administration is considered as the safest and easiest route of drug administration. Control release drug delivery system is the emerging trend in the pharmaceuticals and the oral route is most suitable for such kind of drug delivery system. Oral route is more convenient for It all age group including both pediatric and geriatrics. There are various systems which are adopted to deliver drug in a controlled manner to different target sites through oral route. It includes diffusion controlled drug delivery systems; dissolution controlled drug delivery systems, osmotically controlled drug delivery systems, ion-exchange controlled drug delivery systems, hydrodynamically balanced systems, multi-Particulate drug delivery systems and microencapsulated drug delivery system. The systems are formulated using different natural, semi-synthetic and synthetic polymers. The purpose of the review is to provide information about the orally controlled drug delivery system, polymers which are used to formulate these systems and characterizations of one of the most convenient dosage form which is the tablets. 

  14. 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.

  15. 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.

  16. Tailoring liquid crystalline lipid nanomaterials for controlled release of macromolecules.

    Science.gov (United States)

    Bisset, Nicole B; Boyd, Ben J; Dong, Yao-Da

    2015-11-10

    Lipid-based liquid crystalline materials are being developed as drug delivery systems. However, the use of these materials for delivery of large macromolecules is currently hindered by the small size of the water channels in these structures limiting control over diffusion behaviour. The addition of the hydration-modulating agent, sucrose stearate, to phytantriol cubic phase under excess water conditions incrementally increased the size of these water channels. Inclusion of oleic acid enabled further control of swelling and de-swelling of the matrix via a pH triggerable system where at low pH the hexagonal phase is present and at higher pH the cubic phase is present. Fine control over the release of various sized model macromolecules is demonstrated, indicating future application to controlled loading and release of large macromolecules such as antibodies. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Synthesis and Insecticidal Activity of Enzyme-Triggered Functionalized Hollow Mesoporous Silica for Controlled Release.

    Science.gov (United States)

    Kaziem, Amir E; Gao, Yunhao; He, Shun; Li, Jianhong

    2017-09-13

    In the present study, enzymatic responsive controlled release formulations (CRFs) were fabricated. The CRFs were achieved by anchoring mechanically interlocked molecules using α-cyclodextrin onto the surface pore rims of hollow mesoporous silica (HMS). The CRFs were characterized using Fourier transform infrared spectroscopy, scanning electron microscopy, transmission electron microscopy, and thermogravimetric analysis. The results showed that the CRFs had extraordinary loading ability for chlorantraniliprole (42% w/w) and could effectively preserve chlorantraniliprole against degradation under thermal conditions and UV radiation. The CRFs have been proven to be enzyme-sensitive. The release ratio of chlorantraniliprole from CRFs can be accelerated observably when external α-amylase was introduced. The persistence of CRFs was evaluated by regular sampling feeding experiment using Plutella xylostella as the target insect. The results showed that the larval mortality of P. xylostella was much higher than that of Coragen under all concentrations after 14 days, which proved that CRFs had remarkable persistence.

  18. Controlled release of doxorubicin from electrospun PEO/chitosan/graphene oxide nanocomposite nanofibrous scaffolds.

    Science.gov (United States)

    Ardeshirzadeh, Behnaz; Anaraki, Nadia Aboutalebi; Irani, Mohammad; Rad, Leila Roshanfekr; Shamshiri, Soodeh

    2015-03-01

    Polyethylene oxide (PEO)/chitosan (CS)/graphene oxide (GO) electrospun nanofibrous scaffolds were successfully developed via electrospinning process for controlled release of doxorubicin (DOX). The SEM analysis of nanofibrous scaffolds with different contents of GO (0.1, 0.2, 0.5 and 0.7wt.%) indicated that the minimum diameter of nanofibers was found to be 85nm for PEO/CS/GO 0.5% nanofibers. The π-π stacking interaction between DOX and GO with fine pores of nanofibrous scaffolds exhibited higher drug loading (98%) and controlled release of the DOX loaded PEO/CS/GO nanofibers. The results of DOX release from nanofibrous scaffolds at pH5.3 and 7.4 indicated strong pH dependence. The hydrogen bonding interaction between GO and DOX could be unstable under acidic conditions which resulted in faster drug release rate in pH5.3. The cell viability results indicated that DOX loaded PEO/CS/GO/DOX nanofibrous scaffold could be used as an alternative source of DOX compared with free DOX to avoid the side effects of free DOX. Thus, the prepared nanofibrous scaffold offers as a novel formulation for treatment of lung cancer.

  19. Controlled Release Inhalable Polymeric Microspheres for Treatment of Pulmonary Arterial Hypertension.

    Science.gov (United States)

    Saigal, Aparna; Ng, Wai Kiong; Tan, Reginald B H; Chan, Sui Yung

    2015-01-01

    Pulmonary arterial hypertension (PAH) is a chronic ailment of the lungs, exhibiting elevated arterial pressure and vascular resistance; with a mean arterial pressure above 25 mmHg at rest and above 30 mmHg during exercise. It is associated with poor prognosis, and its prevalence is estimated to be 15 cases per one million. The current treatment options for PAH are discussed with the prostanoid class of drugs being the most effective. The latter drugs act by dilating systemic and pulmonary arterial vascular beds and, with sustained long-term usage, altering pulmonary remodelling. They are administered as IV infusions or inhalation solutions. Despite their clinical effectiveness, prostanoids have short half-lives requiring frequent administration of 6-9 times daily and thus suffer from poor compliance. Controlled release inhalation delivery systems for treatment of PAH, ranging from liposomes, biodegradable nano- and microparticles, formation of co-precipitates and complexation with cyclodextrins, are explored. Arising from these formulation strategies, we developed novel polymeric microspheres for inhalation to reduce dosing frequency and improve medication compliance. These microspheres are designed with release modifiers, to reside in the lung which is the site of drug action for a longer duration so as to release the drug slowly and consistently over a prolonged period. This could lead to the development of the first commercially available controlled release inhalation product.

  20. 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.

  1. Halloysite clay nanotubes for controlled release of protective agents.

    Science.gov (United States)

    Lvov, Yuri M; Shchukin, Dmitry G; Möhwald, Helmuth; Price, Ronald R

    2008-05-01

    Halloysite aluminosilicate nanotubes with a 15 nm lumen, 50 nm external diameter, and length of 800 +/- 300 nm have been developed as an entrapment system for loading, storage, and controlled release of anticorrosion agents and biocides. Fundamental research to enable the control of release rates from hours to months is being undertaken. By variation of internal fluidic properties, the formation of nanoshells over the nanotubes and by creation of smart caps at the tube ends it is possible to develop further means of controlling the rate of release. Anticorrosive halloysite coatings are in development and a self-healing approach has been developed for repair mechanisms through response activation to external impacts. In this Perspective, applications of halloysite as nanometer-scale containers are discussed, including the use of halloysite tubes as drug releasing agents, as biomimetic reaction vessels, and as additives in biocide and protective coatings. Halloysite nanotubes are available in thousands of tons, and remain sophisticated and novel natural nanomaterials which can be used for the loading of agents for metal and plastic anticorrosion and biocide protection.

  2. Control of contents and release kinetics in block copolymer vesicles

    Science.gov (United States)

    Eisenberg, Adi

    2005-03-01

    Block copolymer vesicles have received considerable attention recently because of a wide range of potential applications. In our group, the thermodynamic aspects of vesicle formation, including curvature stabilization, as well as active loading and release from vesicles have been the focus of recent research. The vesicles are prepared from an amphiphilic diblock copolymer such as polystyrene-block-poly(acrylic acid) at a low pH (2.5) by adding water to a solution in a common solvent; then the extenal pH is raised to 6.5, and the compound, such as doxorubicin or another amine, is added. Since the compund inside the vesicle becomes ionized at the low pH, it can only escape at a rate very much slower than that of the loading process. The permeability of the wall can be controlled by the presence of plasticizers for the polystyrene wall; the plasticizers partition between the wall and the external aqueous solution with a known partition coefficient, and can be removed from the wall by dialysis. Release is then studied under perfect sink conditions and is diffusional. It is noteworthy that the rates of both loading and release can be varied by more than two orders of magnitude by controlling the plasticizer content. Also, between the loading and release processes, the vesicle wall can be hardened by removal of the plasticizer by dialysis. This degree of control makes block copolymer vesicles a promising delivery vehicle for a range of materials, including drugs.

  3. CONTROLLED RELEASE FROM PDMAEMA GELS PREPARED BY GAMMA RADIATION

    Institute of Scientific and Technical Information of China (English)

    Ning Liu; Min Yi; Shuang-ji Chen; Hong-fei Ha

    2002-01-01

    Poly(N,N-dimethylaminoethyl methacrylate) (polyDMAEMA) hydrogels prepared by γ-irradiation showed obvious temperature-sensitivity in a temperature range of 38-40℃ and pH-sensitivity at pH = 2.5. They also showed electric response behavior although it was not typical. The hydrogels were used in controlled release at different pH, temperature, and electric voltage. The release rates of methylene blue (MB) from the gels at 52℃ and pH = 1.24 were faster than those at 20℃ and pH = 10.56, respectively. In addition, the release rate at a field voltage of 5.0 was also faster than that without electric field.

  4. Optogenetic control of serotonin and dopamine release in Drosophila larvae.

    Science.gov (United States)

    Xiao, Ning; Privman, Eve; Venton, B Jill

    2014-08-20

    Optogenetic control of neurotransmitter release is an elegant method to investigate neurobiological mechanisms with millisecond precision and cell type-specific resolution. Channelrhodopsin-2 (ChR2) can be expressed in specific neurons, and blue light used to activate those neurons. Previously, in Drosophila, neurotransmitter release and uptake have been studied after continuous optical illumination. In this study, we investigated the effects of pulsed optical stimulation trains on serotonin or dopamine release in larval ventral nerve cords. In larvae with ChR2 expressed in serotonergic neurons, low-frequency stimulations produced a distinct, steady-state response while high-frequency patterns were peak shaped. Evoked serotonin release increased with increasing stimulation frequency and then plateaued. The steady-state response and the frequency dependence disappeared after administering the uptake inhibitor fluoxetine, indicating that uptake plays a significant role in regulating the extracellular serotonin concentration. Pulsed stimulations were also used to evoke dopamine release in flies expressing ChR2 in dopaminergic neurons and similar frequency dependence was observed. Release due to pulsed optical stimulations was modeled to determine the uptake kinetics. For serotonin, Vmax was 0.54 ± 0.07 μM/s and Km was 0.61 ± 0.04 μM; and for dopamine, Vmax was 0.12 ± 0.03 μM/s and Km was 0.45 ± 0.13 μM. The amount of serotonin released per stimulation pulse was 4.4 ± 1.0 nM, and the amount of dopamine was 1.6 ± 0.3 nM. Thus, pulsed optical stimulations can be used to mimic neuronal firing patterns and will allow Drosophila to be used as a model system for studying mechanisms underlying neurotransmission.

  5. Design and Comparative Evaluation of In-vitro Drug Release, Pharmacokinetics and Gamma Scintigraphic Analysis of Controlled Release Tablets Using Novel pH Sensitive Starch and Modified Starch- acrylate Graft Copolymer Matrices

    OpenAIRE

    Kumar, Pankaj; Ganure, Ashok Laxmanrao; Subudhi, Bharat Bhushan; Shukla, Shubhanjali

    2015-01-01

    The present investigation deals with the development of controlled release tablets of salbutamol sulphate using graft copolymers (St-g-PMMA and Ast-g-PMMA) of starch and acetylated starch. Drug excipient compatibility was spectroscopically analyzed via FT-IR, which confirmed no interaction between drug and other excipients. Formulations were evaluated for physical characteristics like hardness, friability, weight variations, drug release and drug content analysis which satisfies all the pharm...

  6. Highly Efficient Thermoresponsive Nanocomposite for Controlled Release Applications

    Science.gov (United States)

    Yassine, Omar; Zaher, Amir; Li, Er Qiang; Alfadhel, Ahmed; Perez, Jose E.; Kavaldzhiev, Mincho; Contreras, Maria F.; Thoroddsen, Sigurdur T.; Khashab, Niveen M.; Kosel, Jurgen

    2016-06-01

    Highly efficient magnetic release from nanocomposite microparticles is shown, which are made of Poly (N-isopropylacrylamide) hydrogel with embedded iron nanowires. A simple microfluidic technique was adopted to fabricate the microparticles with a high control of the nanowire concentration and in a relatively short time compared to chemical synthesis methods. The thermoresponsive microparticles were used for the remotely triggered release of Rhodamine (B). With a magnetic field of only 1 mT and 20 kHz a drug release of 6.5% and 70% was achieved in the continuous and pulsatile modes, respectively. Those release values are similar to the ones commonly obtained using superparamagnetic beads but accomplished with a magnetic field of five orders of magnitude lower power. The high efficiency is a result of the high remanent magnetization of the nanowires, which produce a large torque when exposed to a magnetic field. This causes the nanowires to vibrate, resulting in friction losses and heating. For comparison, microparticles with superparamagnetic beads were also fabricated and tested; while those worked at 73 mT and 600 kHz, no release was observed at the low field conditions. Cytotoxicity assays showed similar and high cell viability for microparticles with nanowires and beads.

  7. Highly Efficient Thermoresponsive Nanocomposite for Controlled Release Applications

    KAUST Repository

    Yassine, Omar

    2016-06-23

    Highly efficient magnetic release from nanocomposite microparticles is shown, which are made of Poly (N-isopropylacrylamide) hydrogel with embedded iron nanowires. A simple microfluidic technique was adopted to fabricate the microparticles with a high control of the nanowire concentration and in a relatively short time compared to chemical synthesis methods. The thermoresponsive microparticles were used for the remotely triggered release of Rhodamine (B). With a magnetic field of only 1 mT and 20 kHz a drug release of 6.5% and 70% was achieved in the continuous and pulsatile modes, respectively. Those release values are similar to the ones commonly obtained using superparamagnetic beads but accomplished with a magnetic field of five orders of magnitude lower power. The high efficiency is a result of the high remanent magnetization of the nanowires, which produce a large torque when exposed to a magnetic field. This causes the nanowires to vibrate, resulting in friction losses and heating. For comparison, microparticles with superparamagnetic beads were also fabricated and tested; while those worked at 73 mT and 600 kHz, no release was observed at the low field conditions. Cytotoxicity assays showed similar and high cell viability for microparticles with nanowires and beads.

  8. Release Characteristics of Different N Forms in an Uncoated Slow/Controlled Release Compound Fertilizer

    Institute of Scientific and Technical Information of China (English)

    DONG Yan; WANG Zheng-yin

    2007-01-01

    This study examined the release characteristics of different N forms in an uncoated slow/controlled-release compound fertilizer (UCRF) and the N uptake and N-use efficiency by rice plants. Water dissolution, soil leaching, and pot experiments were employed. The dynamics of N release from the UCRF could be quantitatively described by three equations: the first-order kinetics equation [Nt = N0 (1-e-kt)], Elovich equation (Nt = a + blnt), and parabola equation (Nt = a + bt0.5), with the best fitting by the first-order kinetics equation for different N (r= 0.9569**-0.9999**). The release potentials (N0 values estimated by the first-order kinetics equation) of different N in the UCRF decreased in the order of total N > DON > urea-N > NH4+-N > NO3--N in water, and total N > NH4+-N > DON > urea-N > NO3--N in soil, respectively,being in accordance with cumulative amounts of N release. The constants of N release rate (k values and b values) for different N forms were in decreasing order of total N > DON > NH4+-N > NO3--N in water, whereas the k values were urea-N >DON > NH4+-N > total N > NO3--N, and the b values were total N > NH4+-N > DON > NO3--N > urea-N in soil. Compared with a common compound fertilizer, the N-use efficiency, N-agronomy efficiency, and N-physiological efficiency of the UCRF were increased by 11.4%, 8.32 kg kg-1, and 5.17 kg kg-1, respectively. The ratios of different N to total N in the UCRF showed significant correlation with N uptake by rice plants. The findings showed that the first-order kinetics equation [Nt=N0(1-e-kt)] could be used to describe the release characteristics of different N forms in the fertilizer. The UCRF containing different N forms was more effective in facilitating N uptake by rice compared with the common compound fertilizer containing single urea-N form.

  9. Normal-release and controlled-release oxycodone: pharmacokinetics, pharmacodynamics, and controversy.

    Science.gov (United States)

    Davis, Mellar P; Varga, James; Dickerson, Duke; Walsh, Declan; LeGrand, Susan B; Lagman, Ruth

    2003-02-01

    Oxycodone has become one of the most popular opioids in the United States. It is superior to morphine in oral absorption and bioavailability, and similar in terms of protein binding and lipophilicity. Gender more than age influences oxycodone elimination. Unlike morphine, oxycodone is metabolized by the cytochrome isoenzyme CYP2D6, which is severely impaired by liver dysfunction. Controlled-release (CR) oxycodone has become one of the most frequently utilized sustained-release opioids in the United States. Both its analgesic benefits and its side effects are similar to those of CR morphine. CR oxycodone is similar to morphine and other opioids in its abuse potential. Deaths attributable to oxycodone are usually associated with polysubstance abuse in which oxycodone is combined with psychostimulants, other opioids, benzodiazepines or alcohol. Oxycodone's kappa receptor binding has little role in abuse or addiction. The cost of CR oxycodone is prohibitive for most American hospices.

  10. Mechanism of controlled release kinetics from medical devices

    Directory of Open Access Journals (Sweden)

    A. Raval

    2010-06-01

    Full Text Available Utilization of biodegradable polymers for controlled drug delivery has gained immense attention in the pharmaceutical and medical device industry to administer various drugs, proteins and other bio-molecules both systematically and locally to cure several diseases. The efficacy and toxicity of this local therapeutics depends upon drug release kinetics, which will further decide drug deposition, distribution, and retention at the target site. Drug Eluting Stent (DES presently possesses clinical importance as an alternative to Coronary Artery Bypass Grafting due to the ease of the procedure and comparable safety and efficacy. Many models have been developed to describe the drug delivery from polymeric carriers based on the different mechanisms which control the release phenomenon from DES. Advanced characterization techniques facilitate an understanding of the complexities behind design and related drug release behavior of drug eluting stents, which aids in the development of improved future drug eluting systems. This review discusses different drug release mechanisms, engineering principles, mathematical models and current trends that are proposed for drug-polymer coated medical devices such as cardiovascular stents and different analytical methods currently utilized to probe diverse characteristics of drug eluting devices.

  11. Controlled Release of Agrochemicals Intercalated into Montmorillonite Interlayer Space

    Directory of Open Access Journals (Sweden)

    Harrison Wanyika

    2014-01-01

    Full Text Available Periodic application of agrochemicals has led to high cost of production and serious environmental pollution. In this study, the ability of montmorillonite (MMT clay to act as a controlled release carrier for model agrochemical molecules has been investigated. Urea was loaded into MMT by a simple immersion technique while loading of metalaxyl was achieved by a rotary evaporation method. The successful incorporation of the agrochemicals into the interlayer space of MMT was confirmed by several techniques, such as, significant expansion of the interlayer space, reduction of Barrett-Joyner-Halenda (BJH pore volumes and Brunauer-Emmett-Teller (BET surface areas, and appearance of urea and metalaxyl characteristic bands on the Fourier-transform infrared spectra of the urea loaded montmorillonite (UMMT and metalaxyl loaded montmorillonite (RMMT complexes. Controlled release of the trapped molecules from the matrix was done in water and in the soil. The results reveal slow and sustained release behaviour for UMMT for a period of 10 days in soil. For a period of 30 days, MMT delayed the release of metalaxyl in soil by more than 6 times. It is evident that MMT could be used to improve the efficiency of urea and metalaxyl delivery in the soil.

  12. Controlled Release of Agrochemicals Intercalated into Montmorillonite Interlayer Space

    Science.gov (United States)

    2014-01-01

    Periodic application of agrochemicals has led to high cost of production and serious environmental pollution. In this study, the ability of montmorillonite (MMT) clay to act as a controlled release carrier for model agrochemical molecules has been investigated. Urea was loaded into MMT by a simple immersion technique while loading of metalaxyl was achieved by a rotary evaporation method. The successful incorporation of the agrochemicals into the interlayer space of MMT was confirmed by several techniques, such as, significant expansion of the interlayer space, reduction of Barrett-Joyner-Halenda (BJH) pore volumes and Brunauer-Emmett-Teller (BET) surface areas, and appearance of urea and metalaxyl characteristic bands on the Fourier-transform infrared spectra of the urea loaded montmorillonite (UMMT) and metalaxyl loaded montmorillonite (RMMT) complexes. Controlled release of the trapped molecules from the matrix was done in water and in the soil. The results reveal slow and sustained release behaviour for UMMT for a period of 10 days in soil. For a period of 30 days, MMT delayed the release of metalaxyl in soil by more than 6 times. It is evident that MMT could be used to improve the efficiency of urea and metalaxyl delivery in the soil. PMID:24696655

  13. Development and evaluation of controlled-release buccoadhesive verapamil hydrochloride tablets

    Directory of Open Access Journals (Sweden)

    Emami J.

    2008-05-01

    Full Text Available Background and purpose of the study: Verapamil hydrochloride is a calcium channel blocker which is used in the control of supraventricular arrhythmia, hypertension and myocardial infraction. There are considerable inter-individual variations in serum concencentration of verpamil due to variation in the extent of hepatic metabolism. In this study controlled-release buccoadhesive tablets of verapamil hydrochloride (VPH were prepared in order to achieve constant plasma concentrations, to improve the bioavailability by the avoidance of hepatic first-pass metabolism, and to prevent frequent administration. Materials and methods: Tablets containing fixed amount of VPH were prepared by direct compression method using polymers like carbomer (CP, hydroxypropylmethyl cellulose (HPMC and sodium carboxymethyl cellulose (NaCMC in various combination and ratios and evaluated for thickness, weight variation, hardness, drug content uniformity, swelling, mucoadhesive strength, drug release and possible interaction between ingredients. Results: All tablets were acceptable with regard to thickness, weight variation, hardness, and drug content. The maximum bioadhesive strength was observed in tablets formulated with a combination of CP-NaCMC followed by CP-HPMC and NaCMC-HPMC.  Decreasing the content of CP in CP-HPMC tablets or NaCMC in CP-NaCMC or NaCMC-HPMC systems resulted in decrease in detachment forces. Lower release rates were observed by lowering the content of CP in CP-HPMC containing formulations or NaCMC in tablets which contained CP-NaCMC or NaCMC-HPMC. The release behavior was non-Fickian controlled by a combination of diffusion and chain relaxation mechanisms and best fitted zero-order kinetics. Conclusion: The buccoadhesive VPH tablets containing 53% CP and 13.3% HPMC showed suitable release kinetics (n = 0.78, K0 zero order release = 4.11 mg/h, MDT = 5.66 h and adhesive properties and did not show any interaction between polymers and drug based on

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

    Science.gov (United States)

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

    2017-11-01

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

  15. Commercial formulation of Metarhizium anisopliae for the control of Rhipicephalus microplus in a pen study.

    Science.gov (United States)

    Camargo, Mariana G; Marciano, Allan F; Sá, Fillipe A; Perinotto, Wendell M S; Quinelato, Simone; Gôlo, Patrícia S; Angelo, Isabele C; Prata, Márcia C A; Bittencourt, Vânia R E P

    2014-09-15

    The present study evaluated, for the first time, the effect of the commercial formulation Metarril(®) SP Organic of Metarhizium anisopliae plus 10% mineral oil to control Rhipicephalus microplus in a pen study. Three groups were formed with six animals each: the first group was exposed to Metarril(®) plus 10% mineral oil and 1% Tween 80; the second group was exposed to sterile distilled water, mineral oil and Tween 80 (oil control group); and the third group received no treatment (control group). The fungal formulation contained 1 × 10(8)conidiaml(-1). Each animal was sprayed with 3L of formulation. Fallen ticks were counted daily and a sample of 20 engorged females per day was incubated for assessment of biological parameters. Throughout the study period, Metarril(®) oil-based formulation showed an efficacy ranging from 19.20% to 67.39% in comparison with the control group; and from 8.18% to 61.38% in comparison with the oil control group. The average efficacy of Metarril(®) oil-based formulation was 47.74% and 40.89% in comparison with control and oil control groups, respectively. Changes in the biological parameters of engorged R. microplus females were observed in the first three days after treatment, with a significant reduction in hatching percentage and egg production index. We concluded that Metarril(®) SP Organic plus 10% mineral oil was efficient against R. microplus in pen studies. However, further in vivo studies are required to increase the efficacy and to establish a protocol for the use of this product in the field against the cattle tick.

  16. Multilayer laminar co-extrudate as a novel controlled release dosage form.

    Science.gov (United States)

    Müllers, Katrin C; Wahl, Martin A; Pinto, João F

    2013-07-16

    Design of a new dosage form manufactured by laminar extrusion for oral administration of drugs. Different mixtures of materials (microcrystalline cellulose [MCC], hydroxypropyl methylcellulose [HPMC], lactose [LAC], dicalcium phosphate [DCP], coumarin [COU], propranolol hydrochloride [PRO], water [W]) were prepared prior to laminar extrusion. Mono, bi and tri layer extrudates were manufactured and evaluated for extrudability, drying, water uptake and swelling ability and in vitro characterization of the drug release. Good quality extrudates were manufactured with higher HPMC molecular weight and fraction in formulation at an extrusion rate of 400 mm/min and slow drying (forced air stream), otherwise surface roughness, thickness in-homogeneity, bending and shark skin were present in the extrudates. Swelling of extrudates was dependent on HPMC fraction and molecular weight (60% up to 90% weight gain for low and high polymer chains, respectively) and the presence of either MCC or DCP. The release of drug was dependent on its solubility (PRO>COU), the fraction of HPMC (low>high fractions), the type of diluent (DCP>MCC) and number of layers (1>2>3 layers). By designing the number and type of layers, dosage forms with well-defined release-kinetics can be tailored. The study has shown the ability of the technology of extrusion to manufacture a controlled release dosage form in a continuous fashion.

  17. 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

  18. Are fluoride releasing dental materials clinically effective on caries control?

    Science.gov (United States)

    Cury, Jaime Aparecido; de Oliveira, Branca Heloisa; dos Santos, Ana Paula Pires; Tenuta, Livia Maria Andaló

    2016-03-01

    (1) To describe caries lesions development and the role of fluoride in controlling disease progression; (2) to evaluate whether the use of fluoride-releasing pit and fissure sealants, bonding orthodontic agents and restorative materials, in comparison to a non-fluoride releasing material, reduces caries incidence in children or adults, and (3) to discuss how the anti-caries properties of these materials have been evaluated in vitro and in situ. The search was performed on the Cochrane Database of Systematic Reviews and on Medline via Pubmed. Caries is a biofilm-sugar dependent disease and as such it provokes progressive destruction of mineral structure of any dental surface - intact, sealed or restored - where biofilm remains accumulated and is regularly exposed to sugar. The mechanism of action of fluoride released from dental materials on caries is similar to that of fluoride found in dentifrices or other vehicles of fluoride delivery. Fluoride-releasing materials are unable to interfere with the formation of biofilm on dental surfaces adjacent to them or to inhibit acid production by dental biofilms. However, the fluoride released slows down the progression of caries lesions in tooth surfaces adjacent to dental materials. This effect has been clearly shown by in vitro and in situ studies but not in randomized clinical trials. The anti-caries effect of fluoride releasing materials is still not based on clinical evidence, and, in addition, it can be overwhelmed by fluoride delivered from dentifrices. Copyright © 2015 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

  19. Controlled exosome release from the retinal pigment epithelium in situ.

    Science.gov (United States)

    Locke, Christina J; Congrove, Nicole R; Dismuke, W Michael; Bowen, Trent J; Stamer, W Daniel; McKay, Brian S

    2014-12-01

    Retinal Pigment Epithelial cells (RPE) express both GPR143 and myocilin, which interact in a signal transduction-dependent manner. In heterologous systems, activation of GPR143 with ligand causes transient recruitment of myocilin to internalized receptors, which appears to be the entry point of myocilin to the endocytic pathway. In some but not all cells, myocilin also traffics through the multivesicular body (MVB) and is released on the surface of exosomes in a signal transduction-dependent fashion. Little is known regarding the role of exosomes in RPE, but they likely serve as a mode of communication between the RPE and the outer retina. In this study, we used posterior poles with retina removed from fresh human donor eyes as a model to test the relationship between GPR143, myocilin, and exosomes in an endogenous system. We isolated exosomes released by RPE using differential centrifugation of media conditioned by the RPE for 25 min, and then characterized the exosomes using nanoparticle tracking to determine the number and size of the exosomes. Next, we tested whether ligand stimulation of GPR143 using l-DOPA altered RPE exosome release. Finally, we investigated whether myocilin was present on the exosomes released by RPE and whether l-DOPA stimulation of GPR143 caused recruitment of myocilin to the endocytic pathway, as we have previously observed using cultured cells. Activation of GPR143 halted RPE exosome release, while simultaneously recruiting myocilin to the endocytic compartment. Together, our results indicate that GPR143 and myocilin function in a signal transduction system that can control exosome release from RPE.

  20. 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.

  1. Hybrid Porous Materials for Controlled Release and Catalysis

    OpenAIRE

    Liu, Rui

    2010-01-01

    First reported in 1992, ordered mesoporous materials exhibit unique features, such as regular pore geometry, high surface area, and large pore volume, and have shown great potential in various applications. This dissertation combines the knowledge from the field of ordered mesoporous materials and several other research areas to design advanced hybrid porous materials for controlled release and catalysis applications.The demand for better treatment of illness has led to ever-increasing effort...

  2. Smart nanofibers with a photoresponsive surface for controlled release.

    Science.gov (United States)

    Fu, Guo-Dong; Xu, Li-Qun; Yao, Fang; Li, Guo-Liang; Kang, En-Tang

    2009-11-01

    A novel photocontrolled "ON-OFF" release system for the alpha-cyclodextrin-5-fluorouracial (alpha-CD-5FU) prodrug, based on host-guest interaction on the photoresponsive and cross-linked nanofiber surface, was demonstrated. The nanofibers with a stimuli-responsive surface were electrospun from the block copolymer prepared via controlled radical polymerization, followed by surface modification via "Click Chemistry", and loading of the prodrug via host-guest interaction.

  3. Hybrid Porous Materials for Controlled Release and Catalysis

    OpenAIRE

    Liu, Rui

    2010-01-01

    First reported in 1992, ordered mesoporous materials exhibit unique features, such as regular pore geometry, high surface area, and large pore volume, and have shown great potential in various applications. This dissertation combines the knowledge from the field of ordered mesoporous materials and several other research areas to design advanced hybrid porous materials for controlled release and catalysis applications.The demand for better treatment of illness has led to ever-increasing effort...

  4. Development of Metarhizium anisopliae and Beauveria bassiana formulations for control of malaria mosquito larvae

    Directory of Open Access Journals (Sweden)

    Takken Willem

    2011-02-01

    Full Text Available Abstract Background The entomopathogenic fungi Metarhizium anisopliae and Beauveria bassiana have demonstrated effectiveness against anopheline larvae in the laboratory. However, utilising these fungi for the control of anopheline larvae under field conditions, relies on development of effective means of application as well as reducing their sensitivity to UV radiation, high temperatures and the inevitable contact with water. This study was conducted to develop formulations that facilitate the application of Metarhizium anisopliae and Beauveria bassiana spores for the control of anopheline larvae, and also improve their persistence under field conditions. Methods Laboratory bioassays were conducted to test the ability of aqueous (0.1% Tween 80, dry (organic and inorganic and oil (mineral and synthetic formulations to facilitate the spread of fungal spores over the water surface and improve the efficacy of formulated spores against anopheline larvae as well as improve spore survival after application. Field bioassays were then carried out to test the efficacy of the most promising formulation under field conditions in western Kenya. Results When formulated in a synthetic oil (ShellSol T, fungal spores of both Metarhizium anisopliae and Beauveria bassiana were easy to mix and apply to the water surface. This formulation was more effective against anopheline larvae than 0.1% Tween 80, dry powders or mineral oil formulations. ShellSol T also improved the persistence of fungal spores after application to the water. Under field conditions in Kenya, the percentage pupation of An. gambiae was significantly reduced by 39 - 50% by the ShellSol T-formulated Metarhizium anisopliae and Beauveria bassiana spores as compared to the effects of the application of unformulated spores. Conclusions ShellSol T is an effective carrier for fungal spores when targeting anopheline larvae under both laboratory and field conditions. Entomopathogenic fungi formulated with

  5. 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.

  6. A foam formulation of an entomopathogenic fungus for control of boring beetles in avocado orchards

    Science.gov (United States)

    A foam formulation of Beauveria bassiana was adapted to control boring beetles in avocado orchards. The two geographically independent avocado growing areas in the United States are threatened by emerging diseases vectored by boring beetles. In the California growing region, Fusarium dieback is vect...

  7. Port Hamiltonian Formulation of Infinite Dimensional Systems II. Boundary Control by Interconnection

    NARCIS (Netherlands)

    Macchelli, Alessandro; Schaft, Arjan J. van der; Melchiorri, Claudio

    2004-01-01

    In this paper, some new results concerning the boundary control of distributed parameter systems in port Hamiltonian form are presented. The classical finite dimensional port Hamiltonian formulation of a dynamical system has been generalized to the distributed parameter and multi-variable case by ex

  8. Port Hamiltonian formulation of infinite dimensional systems II. Boundary control by interconnection

    NARCIS (Netherlands)

    Macchelli, Alessandro; Schaft, van der Arjan J.; Melchiorri, Claudio

    2004-01-01

    In this paper, some new results concerning the boundary control of distributed parameter systems in port Hamiltonian form are presented. The classical finite dimensional port Hamiltonian formulation of a dynamical system has been generalized to the distributed parameter and multivariable case by ext

  9. Progress in Brassicaceae seed meal formulation and application for replant disease control in organic apple orchards

    Science.gov (United States)

    Brassicaceae seed meals when used independently do not provide uniform or sufficient control of the pathogen complex that incites apple replant disease. Trials were established at multiple sites (STM, SR and Tukey orchards) in Washington State to evaluate the efficacy of seed meal formulations for ...

  10. 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

  11. Rheological behaviour and physical properties of controlled-release gluten-based bioplastics.

    Science.gov (United States)

    Gómez-Martínez, D; Partal, P; Martínez, I; Gallegos, C

    2009-03-01

    Bioplastics based on glycerol, water and wheat gluten have been manufactured in order to determine the effect that mechanical processing and further thermal treatments exert on different thermo-mechanical properties of the biomaterials obtained. An "active agent", KCl was incorporated in these matrices to develop controlled-release formulations. Oscillatory shear, dynamic mechanical thermal analysis (DMTA), diffusion and water absorption tests were carried out in order to study the influence of the above-mentioned treatments on the physico-chemical characteristics and rheological behaviour of these bioplastic samples. Wheat gluten protein-based bioplastics studied in this work present a high ability for thermosetting modification, due to protein denaturation, which may favour the development of a wide variety of biomaterials. Bioplastic hygroscopic properties depend on plasticizer nature and processing procedure, and may be a key factor for industrial applications where water absorption is required. On the other hand, high water absorption and slow KCl release from bioplastic samples (both of them suitable properties in agricultural applications) may be obtained by adding citric acid to a given formulation, at selected processing conditions.

  12. Controlled release of 5-flurouracil from biomedical polyurethanes

    Indian Academy of Sciences (India)

    Reddy Seetharamareddy Harisha; Kallappa Mahadevappa Hosamani; Rangappa Sangappa Keri; Namdev Shelke; Vijay Kumar Wadi; Tejaraj M Aminabhavi

    2010-03-01

    Novel biodegradable aliphatic poly(ether-urethane)s (PEUs) based on pluronic F-68 (PLF68) and castor oil were synthesized by the solution polymerization technique. These polymers were characterized by Fourier transform infrared spectroscopy (FTIR), nuclear magnetic spectroscopy (1HNMR) and gel permeation chromatography (GPC) to confirm the PEU formation and the molecular weight. Moderate molecular weight PEUs were obtained and converted into microspheres by solvent evaporation method to study the controlled release (CR) characteristics for 5-flurouracil (5-FU). PLF-68 acts as amphiphilic filler, which enhances the release of a hydrophobic drug such as 5-FU. Sizes of the microspheres as measured by laser light scattering technique ranged between 15 and 42 m. An increase in the size of particles was observed with increasing molar ratio of PLF-68 with respect to castor oil. The percentage encapsulation efficiency varied between 71 and 98. Surface morphology of the microspheres as studied by scanning electron microscopy (SEM) revealed the spherical nature of the particles with wrinkles on their surfaces. The release of 5-FU through the microspheres was investigated in pH 7.4-phosphate buffer. An increase in release rate was observed with increasing molar ratio of PLF68 with respect to castor oil.

  13. Encapsulation efficiency and controlled release characteristics of crosslinked polyacrylamide particles.

    Science.gov (United States)

    Sairam, Malladi; Babu, V Ramesh; Vijaya, Boya; Naidu, Kumar; Aminabhavi, Tejraj M

    2006-08-31

    Polyacrylamide (pAAm) particles crosslinked with N,N-methylenebis-acrylamide/ethylene glycol dimethacrylate (NNMBA/EGDMA) have been prepared in water-methanol medium by the dispersion polymerization using poly(vinyl pyrrolidone), PVP as a steric stabilizer. 5-fluorouracil an anticancer drug, has been loaded in situ into the crosslinked pAAm particles. Plain as well as drug loaded microparticles have been characterized by differential scanning calorimetry (DSC) and X-ray diffraction studies (XRD) and scanning electron microscopy (SEM). DSC and XRD studies have indicated a molecular level dispersion of the drug in pAAm particles during in situ loading and SEM pictures have shown the formation of spherical and oval-shaped particles. In vitro release of 5-fluorouracil from the crosslinked pAAm particles has been carried out in 7.4 pH buffer medium. Both encapsulation efficiency and release patterns are found to depend on the nature of the crosslinking agent, amount of crosslinking agent used and the amount of drug loaded. In vitro release studies indicated the controlled release of 5-fluorouracil up to 12 h.

  14. Preparation and Characterization of Ionotropic Cross-Linked Chitosan Microparticles for Controlled Release of Aceclofenac

    Directory of Open Access Journals (Sweden)

    N. G. Raghavendra Rao

    2010-04-01

    Full Text Available Aceclofenac, (2-[2-[2-(2, 6-dichlorophenyl aminophenyl] acety] oxyacetic acid a non-steroidal anti-inflammatory drug (NSAID, has been indicated for various conditions like post-traumatic pain, rheumatoid arthritis, ankylosing spondylitis. Multiple-unit systems have been reported to avoid the variations in gastric emptying and different transit rates through gastro-intestinal and spread over a large area preventing exposure of the absorbing site to high drug concentration on chronic dosing. The purpose of this study was therefore to develop aceclofenac loaded chitosan microparticles by ionotropic gelation method. Drug loading efficiency (DLE of microparticles was found between 62.20 to 92.93 % and depended on the formulation variables. Increase in the Tripolyphosphate (TPP concentration, pH of the TPP solution and cross-linking time decreased the drug release. The particle size decreased with increase in cross-linking time and found between the ranges of 1194.1 to 1568.9 µm. Drug release showed slight burst effect in phosphate buffer pH 7.4 in first hour followed by prolonged release for 8 hrs. FTIR and DSC revealed that there was no interaction between drug and polymer. The release data was fitted into first order, zero order and Higuchi model to find release kinetics. The values of regression coefficient r2 were found to be greater (£ 0.9541 for first order than for zero order (£ 0.8740 and the r2 value for Higuchi was £ 0.9805 suggesting diffusion controlled process. The result concluded that TPP-chitosan microparticles developed by ionotropic gelation method might become potential delivery system to prolonging the release of aceclofenac.

  15. Montanide ISA 720 vaccines: quality control of emulsions, stability of formulated antigens, and comparative immunogenicity of vaccine formulations.

    Science.gov (United States)

    Miles, Aaron P; McClellan, Holly A; Rausch, Kelly M; Zhu, Daming; Whitmore, Michael D; Singh, Sanjay; Martin, Laura B; Wu, Yimin; Giersing, Birgitte K; Stowers, Anthony W; Long, Carole A; Saul, Allan

    2005-03-31

    Montanide ISA 720 is an experimental adjuvant, formulated as water-in-oil emulsions, that induces high antibody titers in several animal species. It has been used in human vaccine trials with malaria and HIV vaccines. The heightened response is likely due, in part, to the formation of a depot at the injection site. However, post-formulation modifications were seen with seven proteins tested during storage of ISA 720 formulations at 37 degrees C for 1 week and two proteins stored longer at 4 degrees C. Potency studies in mice, in which the stored vaccines were diluted into placebo emulsions for appropriate dosing, indicated that this instability could lead to loss of immunogenicity in the post-injection depot, limiting the allowable storage time of preformed vaccines. We describe point-of-injection formulation for ISA 720 vaccines that meets the requirement for in vitro stability. For preformed vaccines, addition of glycine or glycylglycine prevented antigen modification on storage at 37 degrees C, providing a potential way of stabilizing antigen/ISA 720 formulations for in vitro storage and the post-injection depot.

  16. 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.

  17. Statistical optimization of controlled release microspheres containing cetirizine hydrochloride as a model for water soluble drugs.

    Science.gov (United States)

    El-Say, Khalid M; El-Helw, Abdel-Rahim M; Ahmed, Osama A A; Hosny, Khaled M; Ahmed, Tarek A; Kharshoum, Rasha M; Fahmy, Usama A; Alsawahli, Majed

    2015-01-01

    The purpose was to improve the encapsulation efficiency of cetirizine hydrochloride (CTZ) microspheres as a model for water soluble drugs and control its release by applying response surface methodology. A 3(3) Box-Behnken design was used to determine the effect of drug/polymer ratio (X1), surfactant concentration (X2) and stirring speed (X3), on the mean particle size (Y1), percentage encapsulation efficiency (Y2) and cumulative percent drug released for 12 h (Y3). Emulsion solvent evaporation (ESE) technique was applied utilizing Eudragit RS100 as coating polymer and span 80 as surfactant. All formulations were evaluated for micromeritic properties and morphologically characterized by scanning electron microscopy (SEM). The relative bioavailability of the optimized microspheres was compared with CTZ marketed product after oral administration on healthy human volunteers using a double blind, randomized, cross-over design. The results revealed that the mean particle sizes of the microspheres ranged from 62 to 348 µm and the efficiency of entrapment ranged from 36.3% to 70.1%. The optimized CTZ microspheres exhibited a slow and controlled release over 12 h. The pharmacokinetic data of optimized CTZ microspheres showed prolonged tmax, decreased Cmax and AUC0-∞ value of 3309 ± 211 ng h/ml indicating improved relative bioavailability by 169.4% compared with marketed tablets.

  18. Improved antimicrobial property and controlled drug release kinetics of silver sulfadiazine loaded ordered mesoporous silica

    Directory of Open Access Journals (Sweden)

    Suman Jangra

    2016-09-01

    Full Text Available The present study deals with the loading of silver sulfadiazine into ordered mesoporous silica material by post-impregnation method and its effect on the in vitro release kinetics and antimicrobial property of the drug. The formulated SBA-15 silica material with rope-like morphology and SBA-15-silver sulfadiazine (SBA-AgSD were characterized by UV–visible spectrophotometer, small and wide-angle powder X-ray diffraction (PXRD, field emission scanning electron microscope (FESEM and high resolution transmission electron microscope (HRTEM. Thermo-gravimetric analysis of SBA-AgSD revealed a high loading amount of 52.87%. Nitrogen adsorption–desorption analysis confirmed the drug entrapment into host material by revealing a reduced surface area (214 m2/g and pore diameter (6.7 nm of the SBA-AgSD. The controlled release of silver sulfadiazine drug from the mesoporous silica to simulated gastric, intestinal and body fluids was evaluated. The Korsmeyer–Peppas model fits the drug release data with the non-Fickian diffusion model and zero order kinetics of SBA-AgSD. The antibacterial performance of the SBA-AgSD was evaluated with respect to Staphylococcus aureus, Bacillus subtilis and Pseudomonas aeruginosa. The controlled drug delivery of the SBA-AgSD revealed improved antibacterial activity, thus endorsing its applicability in effective wound dressing.

  19. Biodegradable hydrophobic-hydrophilic hybrid hydrogels: swelling behavior and controlled drug release.

    Science.gov (United States)

    Wu, Da-Qing; Chu, Chih-Chang

    2008-01-01

    The objective of this work was to investigate a new family of hydrophobic-hydrophilic biodegradable hybrid hydrogels as drug carriers. A series of hydrophobic-hydrophilic biodegradable hybrid hydrogels was formulated via photo means from hydrophobic three-arm poly (epsilon-caprolactone) maleic acid (PGCL-Ma) and hydrophilic dextran maleic acid (Dex-Ma) precursors over a wide range of the two precursors' feed ratio (PGCL-Ma/Dex-Ma at 100:0, 70:30, 50:50, 30:70 and 0:100). A low-molecular-weight and hydrophilic drug, the alpha-7 agonist cocaine methiodide, was used as the model drug for the release study from the hybrid hydrogels in pH 7.4 phosphate buffer solution at 37 degrees C. The swelling data of these hybrid hydrogels depended on the hydrophobic to hydrophilic precursors' feed ratio, and there were several-fold differences in swelling ratios between a pure hydrophilic Dex-Ma and a pure hydrophobic PGCL-Ma hydrogels. The presence of the hydrophobic PGCL-Ma component significantly reduced the initial burst swelling of the hybrid hydrogels. Depending on the two precursors' feed ratios, the swelling data during the early period obeyed either Fickian diffusion (for 50:50 PGCL-Ma/Dex-Ma hydrogel), non-Fickian or anomalous transport (for 70:30 and 100:0 PGCL-Ma/Dex-Ma), or relaxation-controlled (for 30:70 and 0:100 PGCL-Ma/Dex-Ma). A wide range of cocaine methiodide release profiles was achieved by controlling hydrophobic to hydrophilic precursors' feed ratios. Initial drug burst release was significantly reduced as the concentration of the hydrophobic PGCL-Ma component increased in the hybrid hydrogels. The bulk of cocaine methiodide released during the 160-h period was via diffusion-controlled mechanism, while degradation-controlled mechanism dominated thereafter.

  20. Formulation development and evaluation of metronidazole magnetic nanosuspension as a magnetic-targeted and polymeric-controlled drug delivery system

    Energy Technology Data Exchange (ETDEWEB)

    Latha, Subbiah [Department of Pharmaceutical Technology, Anna University Tiruchirappalli, Tiruchirappalli 620 024, Tamil Nadu (India)], E-mail: lathasuba@yahoo.co.in; Selvamani, Palanisamy; Kumar, Chelladurai Senthil; Sharavanan, Palaniappan; Suganya, Govindan [Department of Pharmaceutical Technology, Anna University Tiruchirappalli, Tiruchirappalli 620 024, Tamil Nadu (India); Beniwal, Vijender Singh; Rao, Poduri Rama [Centre for Pharmaceutical Nanotechnology, National Institute of Pharmaceutical Education and Research (NIPER), Mohali 160 062, Punjab (India)

    2009-05-15

    A nanosuspension of magnetically tagged metronidazole was developed by the solvent displacement method coupled with ultrasonication and was evaluated for its physicochemical properties. The drug release from metronidazole magnetic nanosuspension at pH 1.2 and 7.0 shows maximum correlation coefficient for zero order and Higuchi model, respectively. The anthelmintic activity of the formulated metronidazole magnetic nanosuspension was evaluated on Indian earthworms (Pheretima poi). Metronidazole magnetic nanosuspension at a dose of 10 and 50 mg/ml shortened by 31% and 34%, respectively, the mean time to death of the earthworms when compared against a non-magnetic metronidazole suspension. Thus, the developed metronidazole magnetic nanosuspension showed potent, controlled and targeted drug action and might be a good therapeutic avenue in combating infectious GI disorders.

  1. Formulation development and evaluation of metronidazole magnetic nanosuspension as a magnetic-targeted and polymeric-controlled drug delivery system

    Science.gov (United States)

    Latha, Subbiah; Selvamani, Palanisamy; Kumar, Chelladurai Senthil; Sharavanan, Palaniappan; Suganya, Govindan; Beniwal, Vijender Singh; Rao, Poduri Rama

    2009-05-01

    A nanosuspension of magnetically tagged metronidazole was developed by the solvent displacement method coupled with ultrasonication and was evaluated for its physicochemical properties. The drug release from metronidazole magnetic nanosuspension at pH 1.2 and 7.0 shows maximum correlation coefficient for zero order and Higuchi model, respectively. The anthelmintic activity of the formulated metronidazole magnetic nanosuspens