Box-Behnken效应面法优化塞来昔布微球制备工艺

目的：制备塞来昔布聚乳酸-羟基乙酸共聚物（PLGA）载药微球,优化其处方和制备工艺,考察其体外释药行为。方法：分别以油相中PLGA浓度、水相PVA浓度和油/水相体积比为考察因素,以包封率为考察指标,采用Box-Behnken效应面法优化塞来昔布微球的处方和工艺;透析袋法评估其体外释放能力。结果：塞来昔布PLGA微球的最佳处方工艺条件为：PLGA浓度75 g·L^-1,水相PVA体积分数1.5%,油/水相体积比1∶30。所制备的微球形态圆整,大小均一,实测包封率为66.1%,与预测值67.3%相比,偏差为1.8%。最优处方体外14 d累积释药56%,体外释放曲线符合Higuchi方程。结论：Box-Behnken效应面法简便可行,可用于优化塞来昔布PLGA微球的制备,微球体外释放具有缓释效果。     

Lacidipine encapsulated gastroretentive microspheres prepared by chemical denaturation for pylorospasm

The purpose of this research work was to formulate and systematically evaluate in vitro performance of mucoadhesive microspheres of lacidipine for treatment of pylorospasm. Lacidipine microspheres containing chitosan were prepared by chemical denaturation using glutaraldehyde as a cross-linking agent. The microspheres were evaluated for physical characteristics such as particle size, particle shape and surface morphology by scanning electron microscopy, drug entrapment efficiency and in vitro mucoadhesion. Results of preliminary trials indicated that the polymer concentration, cross-linking agent and stirring speed had a noticeable effect on size and surface morphology. A central composite design was employed to study the effect of independent variables, polymer concentration (X(1)), volume of glutaraldehyde (X(2)), stirring speed (X(3)) and cross-linking time (X(4)) on dependent variables, drug entrapment efficiency and percentage mucoadhesion. The entrapment efficiency varied from 14-40.82% depending upon the polymer concentration, volume of cross-linker and stirring speed. All batches of microspheres exhibited good mucoadhesive property (73-83%) in the in vitro wash-off test. It was observed that polymer concentration and glutaraldehyde volume had a more significant effect on the dependent variables. Maximum entrapment (36.53%) and mucoadhesion (81.33%) was predicted at 3.5% chitosan, 3 ml glutaraldehyde, 3000 rpm stirring speed and 75 min cross-linking time under optimized process condition. The selected formulation showed controlled release for more than 6 h. The release followed Higuchi kinetics via a Fickian diffusion.     

白藜芦醇PLGA长效注射微球的制备及工艺考察

目的采用乳化溶剂挥发法制备白藜芦醇聚乳酸羟基乙酸[poly(lactic-co-glycolic acid),PL-GA]长效微球,评价各因素对微球性质的影响。方法以微球的包封率、载药量、突释和粒径作为微球的质量评价指标,研究分散相与连续相的体积比、PLGA浓度、聚乙烯醇(polyvinyl alcohol,PVA)浓度、搅拌速度对微球性质的影响,并优化白藜芦醇PLGA微球的制备工艺。结果分散相与连续相的体积比为1∶50时,包封率高,但4 h突释量达到76%,当分散相与连续相体积比由1∶50提升到1∶150时,突释降低了22%;随着聚合物浓度的增加粒径明显增大,突释显著降低;理论载药量对粒径影响不大,在高载药量时突释显著减少;搅拌速度的增加使粒径减小,突释增加;PVA浓度的增加对粒径没有明显的影响,但当PVA的质量浓度从1 g.L-1增加到5 g.L-1时,包封率从93.57%降低到80.31%。结论分散相与连续相的体积比、PLGA浓度、PVA浓度、搅拌速度对微球性质有很大的影响。优化条件下制备的微球形态完整,载药量为(27.86±1.00)%,包封率为(93.57±2.87)%,平均粒径约为21.12μm。白藜芦醇PLGA微球体外释放25 d的累积释药率达(94.04±4.94)%,有望研制成1个月给药1次的给药系统。     

Lacidipine encapsulated gastroretentive microspheres prepared by chemical denaturation for Pylorospasm

Abstract

The purpose of this research work was to formulate and systematically evaluate in vitro performance of mucoadhesive microspheres of lacidipine for treatment of pylorospasm. Lacidipine microspheres containing chitosan were prepared by chemical denaturation using glutaraldehyde as a cross-linking agent. The microspheres were evaluated for physical characteristics such as particle size, particle shape and surface morphology by scanning electron microscopy, drug entrapment efficiency and in vitro mucoadhesion. Results of preliminary trials indicated that the polymer concentration, cross-linking agent and stirring speed had a noticeable effect on size and surface morphology. A central composite design was employed to study the effect of independent variables, polymer concentration (X₁), volume of glutaraldehyde (X₂), stirring speed (X₃) and cross-linking time (X₄) on dependent variables, drug entrapment efficiency and percentage mucoadhesion. The entrapment efficiency varied from 14–40.82% depending upon the polymer concentration, volume of cross-linker and stirring speed. All batches of microspheres exhibited good mucoadhesive property (73–83%) in the in vitro wash-off test. It was observed that polymer concentration and glutaraldehyde volume had a more significant effect on the dependent variables. Maximum entrapment (36.53%) and mucoadhesion (81.33%) was predicted at 3.5% chitosan, 3 ml glutaraldehyde, 3000 rpm stirring speed and 75 min cross-linking time under optimized process condition. The selected formulation showed controlled release for more than 6 h. The release followed Higuchi kinetics via a Fickian diffusion.     

Effects of formulation parameters on encapsulation efficiency and release behavior of thienorphine loaded PLGA microspheres

To develop a long-acting injectable thienorphine biodegradable poly (d, l-lactide-co-glycolide) (PLGA) microsphere for the therapy of opioid addiction, the effects of formulation parameters on encapsulation efficiency and release behavior were studied. The thienorphine loaded PLGA microspheres were prepared by o/w solvent evaporation method and characterized by HPLC, SEM, laser particle size analysis, residual solvent content and sterility testing. The microspheres were sterilized by gamma irradiation (2.5 kGy). The results indicated that the morphology of the thienorphine PLGA microspheres presented a spherical shape with smooth surface, the particle size was distributed from 30.19?±?1.17 to 59.15?±?0.67μm and the drug encapsulation efficiency was influenced by drug/polymer ratio, homogeneous rotation speed, PVA concentration in the water phase and the polymer concentration in the oil phase. These changes were also reflected in drug release. The plasma drug concentration vs. time profiles were relatively smooth for about 25 days after injection of the thienorphine loaded PLGA microspheres to beagle dogs. In vitro and in vivo correlation was established.     

Effects of formulation factors on encapsulation efficiency and release behaviour in vitro of huperzine A-PLGA microspheres

To develop a long-acting injectable huperzine A-PLGA microsphere for the chronic therapy of Alzheimer's disease, the microsphere was prepared by using o/w emulsion solvent extraction evaporation method based on a series of formulation design of the emulsion. The dialysis method was used for release analysis. The encapsulation efficiency and release amount of the microspheres were determined by UV/VIS spectrophotometry. The morphology of the microspheres was observed by scanning electron microscopy. The distribution of the drug within microspheres was observed by a confocal laser scanning microscope. The results indicated that the PLGA 15 000 microspheres possessed a smooth and round appearance with average particle size of 50 microm or so. The encapsulation percentages of microspheres prepared from PLGA 15 000, 20 000 and 30 000 were 62.75, 27.52 and 16.63%, respectively. The drug release percentage during the first day decreased from 22.52% of PLGA 30 000 microspheres to 3.97% of PLGA 15 000 microspheres, the complete release could be prolonged to 3 weeks. The initial burst release of microspheres with higher molecular weight PLGA could be explained by the inhomogeneous distribution of drug within microspheres. The encapsulation efficiency of the microspheres improved as the polymer concentration increase in oil phase and PVA concentration decreased in aqueous phase. The burst release could be controlled by reducing the polymer concentration. Evaporation temperature had a large effect on the drug release profiles. It had better be controlled under 30 degrees C. Within a certain range of particle size, encapsulation efficiency decreased and drug release rate increased with the reducing of the particle size.     

Effects of formulation factors on encapsulation efficiency and release behaviour in vitro of huperzine A-PLGA microspheres

To develop a long-acting injectable huperzine A-PLGA microsphere for the chronic therapy of Alzheimer's disease, the microsphere was prepared by using an o/w emulsion solvent extraction evaporation method based on a series of formulation design of the emulsion. The dialysis method was used for release analysis. The encapsulation efficiency and release amount of the microspheres were determined by a UV/VIS spectrophotometer. The morphology of the microspheres was observed by scanning electron microscopy. The distribution of the drug within microspheres was observed by a confocal laser scanning microscope. The results indicated that the PLGA 15,000 microspheres possessed a smooth and round appearance with average particle size of 50 microm or so. The encapsulation percentages of microspheres prepared from PLGA 15,000, 20,000 and 30,000 were 62.75%, 27.52% and 16.63%, respectively. The drug release percentage during the first day decreased from 22.52% of PLGA 30,000 microspheres to 3.97% of PLGA 15,000 microspheres, the complete release could be prolonged to 3 weeks. The initial burst release of microspheres with higher molecular weight PLGA could be explained by the inhomogeneous distribution of drug within microspheres. The encapsulation efficiency of the microspheres improved as the polymer concentration increased in the oil phase and PVA concentration decreased in the aqueous phase. The burst release could be controlled by reducing the polymer concentration. Evaporation temperature had a large effect on the drug release profiles. It had better be controlled under 30 degrees C. Within a certain range of particle size, encapsulation efficiency decreased and drug release rate increased with the reducing of the particle size.     

Effects of formulation factors on encapsulation efficiency and release behaviour in vitro of huperzine A-PLGA microspheres

To develop a long-acting injectable huperzine A-PLGA microsphere for the chronic therapy of Alzheimer's disease, the microsphere was prepared by using an o/w emulsion solvent extraction evaporation method based on a series of formulation design of the emulsion. The dialysis method was used for release analysis. The encapsulation efficiency and release amount of the microspheres were determined by a UV/VIS spectrophotometer. The morphology of the microspheres was observed by scanning electron microscopy. The distribution of the drug within microspheres was observed by a confocal laser scanning microscope. The results indicated that the PLGA 15?000 microspheres possessed a smooth and round appearance with average particle size of 50?µm or so. The encapsulation percentages of microspheres prepared from PLGA 15?000, 20?000 and 30?000 were 62.75%, 27.52% and 16.63%, respectively. The drug release percentage during the first day decreased from 22.52% of PLGA 30?000 microspheres to 3.97% of PLGA 15?000 microspheres, the complete release could be prolonged to 3 weeks. The initial burst release of microspheres with higher molecular weight PLGA could be explained by the inhomogeneous distribution of drug within microspheres. The encapsulation efficiency of the microspheres improved as the polymer concentration increased in the oil phase and PVA concentration decreased in the aqueous phase. The burst release could be controlled by reducing the polymer concentration. Evaporation temperature had a large effect on the drug release profiles. It had better be controlled under 30°C. Within a certain range of particle size, encapsulation efficiency decreased and drug release rate increased with the reducing of the particle size.     

Design and Evaluation of Niacin Microspheres

Present study aims to prepare and evaluate niacin microspheres. Niacin-ethyl cellulose microspheres were prepared by water-in-oil-in-oil double emulsion solvent diffusion method. Spherical, free flowing microspheres having an entrapment efficiency of 72% were obtained. The effect of polymer-drug ratio, surfactant concentration for secondary emulsion process and stirring speed of emulsification process were evaluated with respect to entrapment efficiency, in vitro drug release behavior and particle size. FT-IR and DSC analyses confirmed the absence of drug-polymer interaction. The in vitro release profile could be altered significantly by changing various processing and formulation parameters to give a controlled release of drug from the microspheres. The percentage yield was 85%, particle size range was 405 to 560 μm. The drug release was controlled for 10 h. The in vitro release profiles from optimized formulations were applied on various kinetic models. The best fit with the highest correlation coefficient was observed in Higuchi model, indicating diffusion controlled principle. The in vitro release profiles of optimized formulation was studied and compared with commercially available niacin extended release formulation.     

β-methasone-containing biodegradable poly(lactide-co-glycolide) acid microspheres for intraarticular injection: effect of formulation parameters on characteristics and in vitro release

A sustained drug release system based on the injectable poly(lactic-co-glycolic acid) (PLGA) microspheres loaded with β-methasone was prepared for localized treatment of rheumatic arthritis. The microscopy and structure of microspheres were characterized by scanning electron microscope (SEM) and Fourier transform infrared (FTIR). The effects of various formulation parameters on the properties of microspheres and in vitro release pattern of β-methasone were also investigated. The results demonstrated that increase in drug/polymer ratio led to increased particle size as well as drug release rate. Increase in PLGA concentration led to increased particle size, but decreased burst release. The drug encapsulation efficiency increased sharply by increasing polyvinyl alcohol (PVA) concentration in the aqueous phase from 1.5 to 2.0%. β-methasone release rate decreased considerately with decreasing OP (organic phase)/AP (aqueous phase) volume ratio. Stirring rate had significantly influence on the particle size and encapsulation efficiency. Independent of formulation parameters, β-methasone was slowly released from the PLGA microspheres over 11 days. The drug release profile of high drug loaded microspheres agree with Higuchi equation with a release mechanism of diffusion and erosion, that of middle drug loaded microspheres best agreed with Hixcon-Crowell equation and controlled by diffusion and erosion as well. The low drug loaded microspheres well fitted to logarithm normal distribution equation with mechanism of purely Fickian diffusion.     

Preparation of poly(lactide-co-glycolide) microspheres and evaluation of pharmacokinetics and tissue distribution of BDMC-PLGA-MS in rats

The aim of the present study was to develop a novel long-acting Poly (lactic-co-glycolic acid) (PLGA)-based microspheres formulation of Bisdemethoxycurcum (BDMC) by emulsion-solvent evaporation method. Meanwhile, the effects of the volume ratio of the dispersed phase and continuous phase, the concentration of PLGA and PVA, the theoretical drug loading and stirring speed were investigated. The mean diameter of the microspheres was 8.5 µm and the size distribution was narrow. The encapsulation efficiency (EE) and drug loading efficiency (DLE) of BDME loaded PLGA microspheres (BDMC-PLGA-MS) was 94.18% and 8.14%, respectively. In an in vitro study of drug release, it can be concluded that the BDMC-PLGA-MS exhibited sustained and long-term release properties for 96 h. Stability studies suggested that the microspheres we prepared had a very good stability. Furthermore, the results of an in vivo study indicated that the BDMC-PLGA-MS had sustained release effect and was mainly distributed in the lung tissue, and less distribution in other tissues, which indicated that microspheres could be an effective parenteral carrier for the delivery of BDMC in lung cancer treatment.     

Development and evaluation of stavudine loaded injectable polymeric particulate systems

Present research investigates the formulation of stavudine loaded biodegradable microspheres from different grades of Poly (D, L Lactide-co-glycolide) as a depot system for parenteral delivery. Prolonged release of stavudine facilitates reduction in symptoms of HIV infection and delay AIDS progression by reducing viral load to undetectable levels. Microspheres were prepared from PLGA 85:15 and PLGA 50:50 (RESOMER(?) 505H) by solvent evaporation technique with different drug/polymer ratios (1:4, 1:10, 1:20, 1:50, 1:100) and a polymer solution/vehicle ratio of 1:2. The effects of various formulation variables like polymer type and concentration, surfactant concentration and drug to polymer ratio on the characteristics of microspheres were evaluated. All thirteen formulations of microspheres were evaluated for yield, entrapment efficiency, particle size and In vitro release studies. Microspheres were characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), X-ray diffraction (XRD), residual solvent analysis and confocal laser scanning microscopy (CLSM). Microspheres showed excellent surface topography with uniform distribution and structural integrity of the drug. Resulting microspheres showed the maximum entrapment efficiency of 68.0 ± 1.62% and mean particle diameter below 100μ. Drug release kinetics data were obtained from various kinetic models and best explained by "Higuchi Kinetic" i.e. drug release was largely governed by diffusion through water-filled pores in the matrix. Korsmeyer-Peppas equation depicted that drug release mechanism is anomalous transport, i.e. diffusion as well as polymer relaxation. Drug release from microspheres exhibited the characteristic release pattern of a monolithic matrix system with a maximum of 80-90% drug release in 6-8 weeks demonstrating the feasibility of prolonged delivery of stavudine using biodegradable microspheres for parenteral depot system.     

5-Fluorouracil-loaded microspheres prepared by spray-drying poly(D,L-lactide) and poly(lactide-co-glycolide) polymers: characterization and drug release

5-Fluorouracil (5-FU), a hydrosoluble anti-neoplastic drug, was encapsulated in microspheres of poly(D,L-lactide) (PLA) and poly(lactide-co-glycolide) (PLGA) polymers using the spray-drying technique, in order to obtain small size microspheres with a significant drug entrapment efficiency. Drug-loaded microspheres included between 47 +/- 11 and 67 +/- 12 microg 5-FU mg(-1) microspheres and the percentage of entrapment efficiency was between 52 +/- 12 and 74 +/- 13. Microspheres were of small size (average diameter: 0.9 +/- 0.4-1.4 +/- 0.8 microm microspheres without drug; 1.1 +/- 0.5-1.7 +/- 0.9 microm 5-FU-loaded microspheres) and their surface was smooth and slightly porous, some hollows or deformations were observed in microspheres prepared from polymers with larger Tg. A fractionation process of the raw polymer during the formation of microspheres was observed as an increase of the average molecular weight and also of Tg of the polymer of the microspheres. The presence of 5-FU did not modify the Tg values of the microspheres. Significant interactions between the drug and each one of the polymers did not take place and total release of the included drug was observed in all cases. The time needed for the total drug release (28-129 h) was in the order PLA > PLGA 75/25 > PLGA 50/50. A burst effect (17-20%) was observed during the first hour and then a period of constant release rate (3.52 +/- 0.82-1.46 +/- 0.26 microg 5-FU h(-1) per milligram of microspheres) up to 8 or 13 h, depending on the polymer, was obtained.     

Preparation and in vivo pharmacokinetics of rhGH-loaded PLGA microspheres

Recombinant human growth hormone (rhGH) therapy must be administered as a daily injection due to its short half-life. To achieve sustained release of rhGH, the preparation of rhGH-loaded PLGA microspheres was investigated, and the influence of various factors on encapsulation efficiency was tested, including rhGH concentration, the ratio of internal phase to organic phase, stirring speed, PVA concentration, surrounding pH value, and the type of emulsifier and organic solvent. A pharmacokinetic study was performed by subcutaneous administration to explore the sustained release effect. It was found that rhGH-loaded PLGA microspheres were prepared with a narrow size distribution, and optimization of the formulation could enhance encapsulation efficiency. FTIR analysis indicated that the activity of rhGH was maintained after encapsulation. The pharmacokinetic behavior of rhGH solutions was consistent with a two-compartment model, which showed fast absorption and distribution. RhGH-loaded PLGA microspheres achieved a higher bioavailability and a long-term effective concentration by controlling the release, and PLGA 50/50 demonstrated favorable AUC compared with PLGA 75/25. Nevertheless, the higher bioavailability of rhGH-loaded PLGA microspheres lacking Span 80 did not predicate better sustained release behavior, indicating that further investigation is needed to explore the use of bioavailability as the standard in evaluating the sustained release characteristics and in vivo behavior of microspheres.     

超微粒制备系统制备利培酮长效注射微球

目的:制备利培酮长效注射微球并进行体外释药动力学考察。方法:选用聚乳酸-羟基乙酸共聚物[poly(D,L-lactic-co-glycolic acid),PLGA]为载体,采用新型超微粒制备系统制备利培酮PLGA微球。以转碟上聚合物析出量、丝状物的形成和微粒表面形态为考察指标单因素实验优化制备工艺参数及处方;观察微球表面形态,测定其粒径、包封率、考察其体外释药动力学。结果:20%和30%载药量的微球表面均光滑圆整,分散性好;其包封率分别为94.7%和93.94%,中值粒径分别为31.65和28.13μm;持续释药时间均可达16 d,释放数据用释放动力学方程拟合符合一级和Higuchi方程。20%载药量微球1 h释药率仅为4.2%,突释率低,且其释放速率和释放时间与市售利醅酮微球(恒德)快速释放期基本一致而无延滞期。结论:超微粒制备系统(UPPS)可单步骤制备长效微球,工艺稳定,简单可行,有望成为一种适合工业微球制备技术。UPPS制备的20%载药量微球可开发为释放2周的制剂,由于无释放延滞期,将比市售品更具临床优势。     

Preparation and characterization of ibuprofen microspheres

Ibuprofen was microencapsulated with Eudragit RS using an o/w emulsion solvent evaporation technique. The effects of three formulation variables including the drug:polymer ratio, emulsifier (polyvinyl alcohol) concentration and organic solvent (chloroform) volume on the entrapment efficiency and microspheres size distribution were examined. The drug release rate from prepared microspheres and the release kinetics were also studied. The results demonstrated that microspheres with good range of particle size can be prepared, depending on the formulation components. The drug:polymer ratio had a considerable effect on the entrapment efficiency. However, particle size distribution of microspheres was more dependent on the volume of chloroform and polyvinyl alcohol concentration rather than the drug:polymer ratio. The drug release pattern showed a burst effect for all prepared microspheres due to the presence of uncovered drug crystals on the surface. It was shown that the release profiles of all formulations showed good correlation with the Higuchi model of release.     

Preparation and characterization of biodegradable urea-loaded microparticles as an approach for transdermal delivery

This work describes the formulation and characterization of urea-loaded microspheres prepared using various polymers such as ethyl cellulose (EC), cellulose acetate phthalate (CAP) and poly (D,L-lactic-co-glycolic acid) (PLGA), along with the utilization of a solvent evaporation technique. The effect of various formulation parameters (i.e. polymer type and concentration, vehicle type, polymer solution/vehicle volume ratio, drug/polymer ratio, homogenizer and stirrer speed, sonication time and speed, type of washing solution, drying and separation method) on the characteristics of microspheres was also evaluated. Results obtained indicated that, in the presence of urea, highest rate of EC microsphere production could be obtained at a drug/polymer ratio of 1:2 and a polymer solution/vehicle volume ratio of 1:50. In some cases, crystallization of urea was observed during the encapsulation process using cellulose derivative polymers. CAP microparticles showed a rough and tortuous surface while EC microparticles had a wider range of particle size. However, with the PLGA polymer, much better desired microparticles with a smaller size range of 1-3 microm were obtained. In general, PLGA microspheres were spherical in shape and possessed smooth surfaces with less pores in comparison with those obtained by the other polymers. The yield of particle production and the extent of urea encapsulation in PLGA particles were measured to be 68.87% +/- 5.3 and 40.5% +/- 3.4, respectively. The release study from PLGA microspheres revealed that up to 70% of the drug was released within a few days, through a four-stage release pattern.     

Preparation and characterization of ibuprofen microspheres

Ibuprofen was microencapsulated with Eudragit RS using an o/w emulsion solvent evaporation technique. The effects of three formulation variables including the drug:polymer ratio, emulsifier (polyvinyl alcohol) concentration and organic solvent (chloroform) volume on the entrapment efficiency and microspheres size distribution were examined. The drug release rate from prepared microspheres and the release kinetics were also studied. The results demonstrated that microspheres with good range of particle size can be prepared, depending on the formulation components. The drug:polymer ratio had a considerable effect on the entrapment efficiency. However, particle size distribution of microspheres was more dependent on the volume of chloroform and polyvinyl alcohol concentration rather than the drug:polymer ratio. The drug release pattern showed a burst effect for all prepared microspheres due to the presence of uncovered drug crystals on the surface. It was shown that the release profiles of all formulations showed good correlation with the Higuchi model of release.     

Preparation and in vitro evaluation of ethyl cellulose microspheres containing stavudine by the double emulsion method

The aim of this study was to formulate and evaluate microspheres of stavudine by water-in-oil-in-oil (w/o/o) double emulsion solvent diffusion method using ethyl cellulose and ethyl cellulose in combination with polyvinyl pyrrolidone. A mixed solvent system consisting of acetonitrile and dichloromethane in an 1: 1 ratio and light liquid paraffin was chosen as primary and secondary oil phase, respectively. Span 80 was used as surfactant for stabilizing the secondary oil phase. The influence of formulation factors like stirring speed, surfactant concentration on particle size and polymer:drug ratio and combination of polymers on drug release characteristics of the microspheres was investigated. The prepared microspheres characterized by micrometric properties, drug loading, Fourier transform infrared spectroscopy, X-ray powder difractometry and scanning electron microscopy. The prepared microspheres were white, free flowing and spherical in shape, stable in nature, with 41-65% of drug entrapment efficiency. The best-fit release kinetics was achieved with Higuchi plot followed by first order and zero order. The release of stavudine was influenced by the drug to polymer ratio, particle size and polymer combination.     

Multiparticulate System for Colon Targeted Delivery of Ondansetron

Targeted delivery of drugs to colon has the potential for local treatment of a variety of colonic diseases. The main objective of the study was to develop a multiparticulate system containing chitosan microspheres for the colon targeted delivery of ondansetron for the treatment of irritable bowel syndrome. This work combines pH-dependent solubility of eudragit S-100 polymers and microbial degradability of chitosan polymers. Chitosan microspheres containing ondansetron were prepared by emulsion cross linking method. The effect of process variables like chitosan concentration, drug-polymer ratio, emulsifier concentration and stirring speed were studied on particle size and entrapment efficiency of chitosan microspheres. In vitro drug release studies in simulated gastro intestinal fluids showed a burst drug release pattern in the initial hour necessitating microencapsulation around the chitosan microspheres. The optimized formulation was then subjected to microencapsulation with eudragit S-100 by solvent evaporation technique. The effect of different coat/core ratio on particle size, drug entrapment efficiency and in vitro drug release were studied. Formulation which contain 1:10 core/coat ratio released lesser amount of drug in the upper gastro intestinal conditions and so selected as best formulation and then subjected to in vitro drug release studies in presence of rat ceacal contents to assess biodegradability of chitosan microspheres in colon. In order to study the drug release mechanism in vitro drug release data was fitted into various kinetic models. Analysis of regression values suggested that the possible drug release mechanism was Peppas model.