Chitosan/pectin polyelectrolyte complexes: Selection of suitable preparative conditions for colon-specific delivery of vancomycin

The influence of polyelectrolyte complexes composed of chitosan and pectin on the release behaviour of vancomycin has been investigated. Polyelectrolyte complexes between chitosan and pectin were prepared in various pH regions and at different molar ratios by mixing solutions of pectin and chitosan with the same ionic strength. The precipitates were collected by spray-drying and tablets were obtained with the different complexes and vancomycin. FT-IR spectra and TGA thermograms were analysed to study the degree of interactive strength between polyions. In vitro swelling, mucoadhesion and release tests were performed in order to investigate the chitosan/pectin complex ability in the delivery of vancomycin in the gastro-intestinal tract. The results confirmed the formation of polyelectrolyte complexes between pectin and chitosan at pH values in the vicinity of the pK_a interval of the two polymers. Chitosan/pectin complexes showed a pH-sensitive swelling ability and drug release behaviour suggesting their possible use for colon-specific localization of vancomycin. Among the different complexes, chitosan/pectin complex prepared in molar ratio of 1:9 showed the highest mucoadhesive properties and a pH-dependent swelling sensitivity suitable for colon-delivery. Moreover, the particular composition of these complexes improved vancomycin availability at alkaline pH on the bases of an enzyme-dependent degradation as confirmed from release studies performed in presence of beta-glucosidase.     

Preparation and characterization of free mixed-film of pectin/chitosan/Eudragit RS intended for sigmoidal drug delivery.

Polyelectrolyte complex (PEC) film between pectin as an anionic polyelectrolyte and chitosan as a cationic species was prepared by blending two polymer solutions at weight ratio of 2:1 and then solvent casting method. Besides pectin/chitosan PEC film, Eudragit RS, pectin/Eudragit RS and pectin/chitosan/Eudragit RS films were also prepared by aforementioned method. In mixed-film formulations, a fixed weight ratio of 1:5 of pectin or pectin/chitosan complex to Eudragit RS was used. Characterizations of pectin/chitosan interaction in solution were investigated by turbidity and viscosity measurement and in the solid state by Fourier transform infrared (FTIR) spectroscopy, wide angle X-ray diffraction (WAXRD) and thermogravimetric analysis (TGA). It was observed that the swelling profile of pectin/chitosan film was pH-dependent and its swelling ratio in phosphate buffer solution (PBS) pH 7.4 was about 2.5-fold higher than that of PBS pH 6.0. Formulation containing only pectin/chitosan could not protect free film from high swelling in the aqueous media, therefore, Eudragit RS as a water-insoluble polymer must be included in the mixed-film. The formation of PEC between pectin and chitosan resulted in a decrease in the crystallinity and thermal stability caused by the interactions between polyions. Drug permeation or diffusion studies were carried out using Plexiglas diffusion cell consisting of donor and acceptor compartments. Theophylline was selected as a model drug to measure permeability coefficient. Drug permeation through pectin/chitosan/Eudragit RS showed a sigmoidal pattern; whereas drug diffusion through pectin/Eudragit RS and Eudragit RS films followed a linear characteristic. The drug permeation through the ternary mixed-film showed a burst release upon exposure to PBS pH 6.0. This mixed-film formulation showed the potential for sigmoidal drug delivery with an initial, controllable slow release followed by a burst release immediately after the change in pH. The burst drug permeation might possibly be due to change in film's porosity.     

Preparation and characterization of drug‐loaded chitosan–tripolyphosphate microspheres by spray drying

The present study reports on the preparation of chitosan–tripolyphosphate (TPP) microspheres by the spray‐drying method using acetaminophen as a model drug substance. Chitosan–TPP microspheres were spherical and had a smooth surface. Perfectly spherical chitosan–TPP microparticles loaded with acetaminophen were obtained in the size range of 3.1–10.1 µm. Spray‐dried chitosan–TPP microspheres were positively charged (zeta potential ranged from +18.4 to +31.8). The encapsulation efficiency of these microspheres was in the range of 48.9–99.5%. The swelling capacity of chitosan–TPP microspheres increased with increases in the molecular weight of chitosan and decreases with increasing volume of 1% wt/vol TPP solution used for the cross‐linking reaction. The effect of chitosan concentration, drug loading, volume of TPP solution used for cross‐linking, and chitosan molecular weight on surface morphology and drug release rate was extensively investigated. Microparticles with spherical shape and slower release rates were obtained from chitosan–TPP microspheres prepared using a higher concentration of chitosan, higher volume of TPP solution, a higher molecular weight chitosan and/or a higher drug loading. Most importantly, the drug release rate was mainly controlled by the chitosan–TPP matrix density and, thus, by the degree of swelling of the hydrogel matrix. Drug release from chitosan–TPP microspheres occurred via diffusion as the best fit for drug release was obtained using the Higuchi equation. Drug Dev. Res. 64:114–128, 2005. © 2005 Wiley‐Liss, Inc.     

Bumadizone calcium dihydrate microspheres compressed tablets for colon targeting: formulation,optimization and in vivo evaluation in rabbits

Abstract

The objective of this study was the development of a colon-targeted microspheres which were compressed into tablets containing the non-steroidal anti-inflammatory bumadizone calcium dihydrate. A 3² full factorial design was adopted for the evaluation of the prepared microspheres. The effect of two independent variables namely polymer type (Eudragit RS100, ethyl cellulose and cellulose acetate butyrate), and drug: polymer ratio (1:1, 9:1 and 18:1) was studied on the entrapment efficiency and in vitro drug release for 12?h. Colon targeting aims to minimize the release of the drug off target area (pH 1.2 and 6.8) and to maximize the release of the drug in target area (pH 7.4). Candidate formulae were compressed into core tablets and colon targeting was achieved using the enzyme-dependent polymer (pectin) as coat in three different concentrations 50, 75 and 90%. Candidate formula F15 (microspheres prepared using BDZ:CAB in a ratio of 18:1 and compressed into tablets using 50% pectin and 50% Avicel in the coat) was able to adequately modulate drug release avoiding drug release in the gastric ambient, and reaching the colonic targeting where 99.7% release was achieved within 12?h following zero-order model. In vivo studies showed that F15 achieved significant decrease in myeloperoxidase activity and inflammation with delayed T_max (4?h) and lower C_max (2700?ng/ml) when compared to marketed product.     

Colon-specific delivery of mesalazine chitosan microspheres

Mesalazine (5-ASA) is a cyclo-oxygenase inhibitor and anti-inflammatory drug effective in Crohn's disease and ulcerative-colitis. As 5-ASA is rapidly absorbed from the small intestine and it is necessary to develop a colon-specific delivery system for it. Coated chitosan microspheres were used for this purpose by an emulsion-solvent evaporation technique based on a multiple w/o/w emulsion. Four hundred milligrams of chitosan solution (3%) in dilute acetic acid (0.5 M) containing 12% 5-ASA was dispersed into 2 ml solution of cellulose acetate butyrate (CAB) in methylene chloride. The primary induced w/o emulsion was dispersed into a 1% PVA aqueous solution to produce a w/o/w multiple emulsion and was stirred for approximately 2.5 h. The produced microspheres were separated, washed and dried. Release of 5-ASA from microspheres was studied in different pHs 1.2, 7.4, 6.8 and 6.8 in the presence of caecal contents of rat. The average size of microspheres was 200 microm. The highest yield efficiency (80%) was seen in medium molecular weight (MW) chitosan with a 1 : 2 core/coat ratio and the greatest loading efficiency (85%) related to the microspheres of the same type of chitosan but with a 1 : 1 core/coat ratio. Decreasing the coat content and increasing chitosan Mw increased the bioadhesion significantly (p < 0.05). Microspheres of chitosan with medium Mw and 1 : 1 core/coat that showed the greatest release of drug (near 80%) in the presence of caecal secretions with a zero-order mechanism, near zero per cent in pH 1.2 after 2 h, max 20% in pH 7.4 after 3 h and near 60% in pH 6.8 after 8 h seem suitable for site-specific delivery of 5-ASA in vitro.     

Colon-specific delivery of mesalazine chitosan microspheres

Mesalazine (5-ASA) is a cyclo-oxygenase inhibitor and anti-inflammatory drug effective in Crohn's disease and ulcerative-colitis. As 5-ASA is rapidly absorbed from the small intestine and it is necessary to develop a colon-specific delivery system for it. Coated chitosan microspheres were used for this purpose by an emulsion-solvent evaporation technique based on a multiple w/o/w emulsion. Four hundred milligrams of chitosan solution (3%) in dilute acetic acid (0.5?M) containing 12% 5-ASA was dispersed into 2?ml solution of cellulose acetate butyrate (CAB) in methylene chloride. The primary induced w/o emulsion was dispersed into a 1% PVA aqueous solution to produce a w/o/w multiple emulsion and was stirred for ～2.5?h. The produced microspheres were separated, washed and dried. Release of 5-ASA from microspheres was studied in different pHs 1.2, 7.4, 6.8 and 6.8 in the presence of caecal contents of rat. The average size of microspheres was 200?µm. The highest yield efficiency (80%) was seen in medium molecular weight (MW) chitosan with a 1?:?2 core/coat ratio and the greatest loading efficiency (85%) related to the microspheres of the same type of chitosan but with a 1?:?1 core/coat ratio. Decreasing the coat content and increasing chitosan Mw increased the bioadhesion significantly (p?<?0.05). Microspheres of chitosan with medium Mw and 1?:?1 core/coat that showed the greatest release of drug (near 80%) in the presence of caecal secretions with a zero-order mechanism, near zero per cent in pH 1.2 after 2?h, max 20% in pH 7.4 after 3?h and near 60% in pH 6.8 after 8?h seem suitable for site-specific delivery of 5-ASA in vitro.     

Pectin/chitosan mixtures as coatings for colon-specific drug delivery: an in vitro evaluation

The ability of a multiple-unit dosage form to reach the colon intact has been investigated, in vitro, using conditions chosen to simulate the pH and times likely to be encountered during transit to the colon. Small tablets were coated with either pectin USP or pectin in a 1:10 mixture with chitosan. Indomethacin and paracetamol were used as model drugs to represent poorly soluble and soluble compounds. Pectin alone was able to protect the cores from premature release, but only when a substantially thick coat was present. Pectin/chitosan mixtures achieved better protection at a lower coat weight. The use of pectinolytic enzymes to simulate breakdown in the colon showed that the pectin/chitosan mixture was susceptible to enzymic breakdown and allowed drug release to occur. The importance of pre-exposure of the tablets to conditions in the upper gastro-intestinal tract prior to exposure to the enzyme was noted.     

Formulation and evaluation of chitosan microspheres of aceclofenac for colon‐targeted drug delivery

The objective of this investigation was to develop novel colon specific drug delivery. Aceclofenac, a NSAID, was successfully encapsulated into chitosan microspheres. Various formulations were prepared by varying the ratio of chitosan, span‐85 and stirring speed and the amount of glutaraldehyde. The SEM study showed that microspheres have smooth surfaces. Microspheres were characterised by Fourier transform infrared (FTIR) spectroscopy and differential scanning calorimetry (DSC) to confirm the absence of chemical interactions between drug and polymer and to know the formation of microspheres structure. The microspheres were evaluated for particle size, encapsulation efficiency, drug loading capacity, mucoadhesion studies, stability studies, in vitro and in vivo drug release studies. Particle sizes, as measured by the laser light scattering technique, were of an average size in the range 41–80 µm. The swelling index was in the range 0.37–0.82 and the entrapment efficiency range was 51–75% for all the formulations. The optimised batch ACM₁₃ released 83.6% at 8 h and 104% at 24 h in SCF containing rat caecal content. Eudragit coated chitosan microspheres prevented the release of the aceclofenac in the physiological environment of the stomach and small intestine and released 95.9±0.34% in the colon. With regard to release kinetics, the data were best fitted with the Higuchi model and showed zero order release with non‐Fickian diffusion mechanism. The in vivo findings suggest that aceclofenac microspheres exhibit a prolonged effect of aceclofenac in rats and produce a significant anti‐inflammatory effect. The findings of the present study conclusively state that chitosan microspheres are promising for colon targeting of aceclofenac to synchronise with chronobiological symptoms of rheumatoid arthritis. Copyright © 2010 John Wiley & Sons, Ltd.     

pH敏感型羧甲基壳聚糖水凝胶的制备及体外释药考察

目的:研制一种新型羧甲基壳聚糖基pH敏感性水凝胶,考察其在药物传输体系中的应用.方法:采用钙离子交联方法制备有良好pH响应性能的羧甲基壳聚糖基水凝胶,并对其pH响应性能进行相关的表征.以磺胺嘧啶钠为模型药物,考察载药水凝胶在不同pH环境条件下(pH =2和pH =7.4)的药物释放行为.结果:所制备的羧甲基壳聚糖水凝胶具有明显的孔洞结构和良好的pH响应性能,在中性磷酸盐缓冲溶液(pH=7.4)中吸水率显著大于在酸性溶液(pH=2)中的吸水率.载有磺胺嘧啶钠的羧甲基壳聚糖水凝胶在中性磷酸盐缓冲溶液(pH=7.4)中的4h的药物累计释放率达到95％,而在酸性溶液(pH=2)中的4h的药物累计释放率却只有50％.结论:本文所制备的羧甲基壳聚糖pH敏感性水凝胶具有良好的孔隙率和pH响应性能,在口服药物传输体系中有一定的应用前景.     

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.     

Sustained release properties of alginate microspheres and tabletted microspheres of diclofenac sodium

This study focused on the properties of diclofenac sodium (DNa) alginate (alg) microspheres and tabletted DNa alg microspheres using different polymers as additives. DNa alginate microspheres were prepared by the emulsification method and different polymers such as Eudragit (Eud) NE 30 D, Eudragit (Eud) RS 30 D and Aquacoat, which were incorporated into alg gel to control the release rate of drug. The release properties of DNa alg microspheres (1:1) were affected by the size, drug load of microspheres and also by the incorporated polymers, pH and ionic strength of dissolution medium. Tabletting of alg microspheres using carrageenan (carr), alg, pectin, NaCMC, tragacanth (trgh) and HPMC as additives in a (50:50) ratio produced tablets with good physical properties and also better controlled release of DNa. Dissolution studies were carried out in pH 7.2 phosphate buffer and phosphate buffers whose pH values were gradually changed from pH 3 to 7.4. The rank order of DNa release from tablets was carr < alg < pectin < NaCMC < trgh < HPMC which relates to the viscosity and swelling properties of polymers. The drug release was very slow from trgh and HPMC based tablets, but addition of carr or alg in different ratios could adjust the release rate of drug.     

Controlled release of vancomycin from freeze-dried chitosan salts coated with different fatty acids by spray-drying

The aim of this study was to describe a controlled drug release system based on chitosan salts for vancomycin hydrochloride delivery. Chitosan aspartate (CH-Asp), chitosan glutamate (CH-Glu) and chitosan hydrochloride (CH-HCl) were prepared by freeze-drying and coated with stearic, palmitic, myristic and lauric acids by spray-drying technique. Vancomycin hydrochloride was used as a peptidic model drug whose sustained release should minimize its inactivation in the upper part of the gastrointestinal tract. This study evaluated, in vitro, the influence of chitosan salts on the release behaviour of vancomycin hydrochloride from the freeze-dried and spray-dried systems at pH 2.0 and 7.4.     

Preparation and evaluation of zinc-pectin-chitosan composite particles for drug delivery to the colon: role of chitosan in modifying in vitro and in vivo drug release

Zinc-pectin-chitosan composite microparticles were designed and developed as colon-specific carrier. Resveratrol was used as model drug due to its potential activity on colon diseases. Formulations were produced by varying different formulation parameters (cross-linking pH, chitosan concentration, cross-linking time, molecular weight of chitosan, and drug concentration). Single-step formulation technique was compared with multi-step technique. Effect of these parameters was investigated on shape, size, weight, weight loss (WL), moisture content (MC), encapsulation efficiency (EE), drug loading (L), and drug release pattern of the microparticles. The formulation conditions were optimized from the drug release study. In vivo pharmacokinetics of the zinc-pectinate particles was compared with the zinc-pectin-chitosan composite particles in rats. Formulations were spherical with 920.48-1107.56 μm size, 21.19-24.27 mg weight of 50 particles, 89.83-94.34% WL, 8.31-13.25% MC, 96.95-98.85% EE, and 17.82-48.31% L. Formulation parameters showed significant influence on drug release pattern from the formulations. Formulation prepared at pH 1.5, 1% chitosan, 120 min cross-linking time, and pectin:drug at 3:1 ratio demonstrated colon-specific drug release. Microparticles were stable at 4 °C and room temperature. Pharmacokinetic study indicated in vivo colon-specific drug release from the zinc-pectin-chitosan composite particles only.     

Metronidazole loaded pectin microspheres for colon targeting

A multiparticulate system having pH-sensitive property and specific enzyme biodegradability for colon-targeted delivery of metronidazole was developed. Pectin microspheres were prepared using emulsion-dehydration technique. These microspheres were coated with Eudragit® S-100 using oil-in-oil solvent evaporation method. The SEM was used to characterize the surface of these microspheres and a distinct coating over microspheres could be seen. The in vitro drug release studies exhibited no drug release at gastric pH, however continuous release of drug was observed from the formulation at colonic pH. Further, the release of drug from formulation was found to be higher in the presence of rat caecal contents, indicating the effect of colonic enzymes on the pectin microspheres. The in vivo studies were also performed by assessing the drug concentration in various parts of the GIT at different time intervals which exhibited the potentiality of formulation for colon targeting. Hence, it can be concluded that Eudragit coated pectin microspheres can be used for the colon specific delivery of drug. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:4229–4236, 2009     

Sustained release properties of alginate microspheres and tabletted microspheres of diclofenac sodium

This study focused on the properties of diclofenac sodium (DNa) alginate (alg) microspheres and tabletted DNa alg microspheres using different polymers as additives. DNa alginate microspheres were prepared by the emulsification method and different polymers such as Eudragit (Eud) NE 30 D, Eudragit (Eud) RS 30 D and Aquacoat, which were incorporated into alg gel to control the release rate of drug. The release properties of DNa alg microspheres (1:1) were affected by the size, drug load of microspheres and also by the incorporated polymers, pH and ionic strength of dissolution medium. Tabletting of alg microspheres using carrageenan (carr), alg, pectin, NaCMC, tragacanth (trgh) and HPMC as additives in a (50:50) ratio produced tablets with good physical properties and also better controlled release of DNa. Dissolution studies were carried out in pH7.2 phosphate buffer and phosphate buffers whose pH values were gradually changed from pH 3 to 7.4. The rank order of DNa release from tablets was carr<alg<pectin<NaCMC<trgh<HPMC which relates to the viscosity and swelling properties of polymers. The drug release was very slow from trgh and HPMC based tablets, but addition of carr or alg in different ratios could adjust the release rate of drug.     

Gamma scintigraphic evaluation of film-coated tablets intended for colonic or biphasic release

The gastrointestinal transit and in vivo drug release behaviour of a film-coated tablet formulation was investigated in five healthy human subjects using the technique of gamma scintigraphy. The film coating system consisted of a mixture of pectin, chitosan and HPMC in a ratio of 6:1:0.37 applied to 750 mg cores at a coat weight gain of 9%. The estimated mean values of the gastric emptying time (62±17 min), small intestinal transit time (219±53 min), ileocaecal junction lag time (79±30 min) and the colon arrival time (345±33 min), were similar to published values for the transit of similar sized tablets in humans. The amount of radioactive tracer released from the labelled tablets was minimal when the tablets were in the stomach and the small intestine. There was increased release of radioactivity when the tablets were in the colon due to increased degradation of the film coatings by pectinolytic enzymes resident in the colon. The pectin/chitosan/HPMC film coating system thus acts as a colonic delivery system.     

Pectin/Ethylcellulose Film Coating Formulations for Colonic Drug Delivery

Purpose. The purpose of the study was to investigate the potential of pectin, ethylcellulose combinations as a practical film coating for colonic delivery. Methods. Combinations of pectin and ethylcellulose, in the form of an aqueous dispersion, were used as coating formulations. Paracetamol cores were used as the substrate. The coatings were assessed by a flow through dissolution system simulating in vivo conditions by changes in pH and residence time. Pectinolytic enzymes were used to simulate the bacterial flora of the colon. Results. Drug release was controlled by the ratio of ethylcellulose to pectin in the film coat. Increasing the proportion of ethylcellulose and increasing the coat weight reduced drug release in pHl and pH7.4 media. The addition of pectinolytic enzymes to pH6 media increased the release of drug. Conclusions. Combinations of ethylcellulose and pectin can provide protection to a drug in the upper g.i. tract while allowing enzymatic breakdown and drug release in the colon.     

Development and in vitro/in vivo evaluation of Zn-pectinate microparticles reinforced with chitosan for the colonic delivery of progesterone

The colon is a promising target for drug delivery owing to its long transit time of up to 78?h, which is likely to increase the time available for drug absorption. Progesterone has a short elimination half-life and undergoes extensive first-pass metabolism, which results in very low oral bioavailability (～25%). To overcome these shortcomings, we developed an oral multiparticulate system for the colonic delivery of progesterone. Zn-pectinate/chitosan microparticles were prepared by ionotropic gelation and characterized for their size, shape, weight, drug entrapment efficiency, mucoadhesion and swelling behavior. The effect of cross-linking pH, cross-linking time and chitosan concentration on progesterone release were also studied. Spherical microparticles having a diameter of 580–720?µm were obtained. Drug entrapment efficiency of ～75–100% was obtained depending on the microparticle composition. Microparticle mucoadhesive properties were dependent on the pectin concentration, as well as the cross-linking pH. Progesterone release in simulated gastric fluids was minimal (3–9%), followed by burst release at pH 6.8 and a sustained phase at pH 7.4. The in vivo study revealed that the microparticles significantly increased progesterone residence time in the plasma and increased its relative bioavailability to ～168%, compared to the drug alone. This study confirms the potential of Zn-pectinate/chitosan microparticles as a colon-specific drug delivery system able to enhance the oral bioavailability of progesterone or similar drugs.     

Chitosan salts as nasal sustained delivery systems for peptidic drugs

The aim of this study was to describe a sustained drug release system based on chitosan salts for vancomycin hydrochloride delivery. Chitosan lactate, chitosan aspartate, chitosan glutamate and chitosan hydrochloride were prepared by spray-drying technique. Vancomycin hydrochloride was used as a model peptidic drug, the nasal sustained release of which should avoid first-pass metabolism in the liver. This in-vitro study evaluated the influence of chitosan salts on the release behaviour of vancomycin hydrochloride from the physical mixtures at pH 5.5 and 7.4. In-vitro release of vancomycin was retarded by chitosan salts and, in particular, chitosan hydrochloride provided the lowest release of vancomycin.     

Glutaraldehyde cross-linked chitosan microspheres for controlled delivery of zidovudine

Zidovudine-Chitosan microspheres were prepared by a suspension cross-linking method. The chitosan was dissolved in 2% acetic acid solution and this solution was dispersed in the light liquid paraffin. Span-80 was used as an emulsifier and glutaraldehyde as cross-linking agent. The prepared microspheres were slight yellow, free flowing and characterized by drug loading, infrared spectroscopy (IR), differential scanning colorimetry (DSC) and scanning electron microscopy (SEM). The in-vitro release studies are performed in pH 7.4 buffer solution. Microspheres produced are spherical and have smooth surfaces, with sizes ranging between 60-210 μm, as evidenced by SEM and particle size analysis. The drug loaded microspheres showed up to 60% of entrapment and release was extended up to 18-24 h. Among all the systems studied, the 35% Glutaraldehyde crosslinked, microspheres with 1 : 6 drug/chitosan ratio showed 75% release at 12 h. The infrared spectra and DSC thermograms showed stable character of zidovudine in the drug loaded microspheres and revealed the absence of drug-polymer interactions. Data obtained from in vitro release were fitted to various kinetic models and high correlation was obtained in the Higuchi model. The drug release was found to be diffusion controlled.