Eudragit-coated dextran microspheres of 5-fluorouracil for site-specific delivery to colon

Objective of the present investigation was to prepare and evaluate the potential of enteric coated dextran microspheres for colon targeting of 5-fluorouracil (5-FU). Dextran microspheres were prepared by emulsification-crosslinking method and the formulation variables studied included different molecular weights of dextran, drug:polymer ratio, volume of crosslinking agent, stirring speed and time. Enteric coating (Eudragit S-100) of dextran microspheres was performed by oil-in-oil solvent evaporation method using different coat:core ratios (4:1 or 8:1). Uncoated and coated dextran microspheres were characterized by particle size, surface morphology, entrapment efficiency, DSC, in vitro drug release in the presence of dextranase and 2% rat cecal contents. The release study of 5-FU from coated dextran microspheres was pH dependent. No release was observed at acidic pH; however, the drug was released quickly where Eudragit starts solublizing there was continuous release of drug from the microspheres. Organ distribution study was suggested that coated dextran microspheres retard the release of drug in gastric and intestinal pH environment and released of drug from microspheres in colon due to the degradation of dextran by colonic enzymes.     

pH triggered delivery of curcumin from Eudragit-coated chitosan microspheres for inflammatory bowel disease: characterization and pharmacodynamic evaluation

Objective: This investigation deals with the development and evaluation (in vitro and in vivo) of pH triggered Eudragit-coated chitosan microspheres of curcumin (CUR) for treating ulcerative colitis.

Methods: CUR-loaded chitosan microspheres were initially prepared by emulsion cross linking method followed by coating with Eudragit S-100. The pharmacodynamics of the developed formulation was analyzed in mice by acetic acid induced colitis model.

Results: The developed microspheres were of uniform spherical shape with high entrapment efficiency. CUR-chitosan microspheres showed less intense peaks compared to free CUR confirming inclusion of drug within microspheres as revealed by X-ray diffractogram. Uncoated CUR-chitosan microspheres exhibited burst release within initial 4?h while microspheres coated with Eudragit S-100 prevented premature release of CUR and showed controlled release up to 12?h following Higuchi model. In vivo organ biodistribution study showed negligible amount of CUR in stomach and small intestine confirming integrity of microsphere in upper gastrointestinal tract (GIT). In vivo study revealed significant reduction in severity and extent of colonic damage with CUR-loaded microspheres as compared to pure CUR which was further confirmed by histopathological study.

Conclusion: In vitro and in vivo studies proved the developed formulations as a promising system for pH-dependent delivery of drug to colon in ulcerative colitis.     

Development and Evaluation of pH-Dependent Micro Beads for Colon Targeting

The purpose of this research was to develop and evaluate multiparticulates of alginate and chitosan hydrogel beads exploiting pH sensitive property for colon-targeted delivery of theophylline. Alginate and chitosan beads were prepared by ionotropic gelation method followed by enteric coating with Eudragit S100. All formulations were evaluated for particle size, encapsulation efficiency, swellability and in vitro drug release.In vitro dissolution studies performed following pH progression method demonstrated that the drug release from coated beads depends on coat weights applied and pH of dissolution media. Mechanism of drug release was found to be swelling and erosion-dependent. The studies showed that formulated alginate and chitosan beads can be used effectively for the delivery of drug to colon and a coat weight of 20% weight gain was sufficient to impart an excellent gastro resistant property to the beads for effective release of drug at higher pH values.     

In vitro evaluation of chondroitin sulphate-chitosan microspheres as carrier for the delivery of proteins

A novel formulation based on chondroitin sulphate/chitosan microspheres (CS/CH) has been investigated for oral delivery of macromolecules using ovalbumin as the model protein (OVA). The microspheres were prepared by a new emulsion-complex coacervation method. Physico-chemical properties of the polymers constituting microparticulate matrix were investigated by IR, DSC, TGA and X-ray diffraction analyses. In vitro tests were performed to evaluate the drug delivery system degradation and the protein release under conditions simulating the intestinal fluids. The ability of colonic enzymes to degrade the microparticulate systems was simulated employing the chondroitinase ABC enzyme. Results showed that the different CS/CH compositions influenced both microparticles stability and the protein release rate. Only the microspheres composed by 1:1 chondroitin sulphate–chitosan ratio achieved an OVA release profile suitable to a possible colon targeting. These microspheres released ～30% of ovalbumin encapsulated in 24 h in the different aqueous media tested, while they released 100% of protein in the presence of chondroitinase. The preliminary results demonstrated that chondroitin sulphate-chitosan microspheres can be a suitable delivery system for protein drug envisaged to oral administration.     

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.     

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     

Ionotropic cross-linked chitosan microspheres for controlled release of ampicillin

The solubility of non cross-linked chitosan in weak acid solutions restricts its utility in microspheres for drug delivery. The primary aim of this study was to produce pentasodium tripolyphosphate cross-linked chitosan microspheres with higher acid resistance for controlled release of ampicillin. The microspheres were prepared by two different microencapsulation procedures (by emulsification and by spray-drying) and characterized by their particle size, surface morphology, stability, drug entrapment efficiency and drug release. The size of the microspheres was <10 microm with a narrow size distribution. The entrapment of ampicillin in the microspheres was more than 80%. Stability of uncross-linked and cross-linked microspheres was affected by the pH of simulated gastric fluid (SGF, pH 1.2) and simulated intestinal fluid (SIF, pH 7.5). The inclusion of the enzymes pepsin and pancreatin did not affect the stability of the microspheres. The inclusion of lysozyme in phosphate buffer saline resulted in increased solubilization. The release of the drug was affected by cross-linking of microspheres with tripolyphosphate (TPP). The cross-linked microspheres were more stable in simulated gastric fluid and showed slower but sustained release of ampicillin. The antimicrobial activity of the released ampicillin was confirmed by Staphylococcus aureus bioassay.     

Bioavailability enhancement of ondansetron after nasal administration of Caesalpinia pulcherrima-based microspheres

Abstract

Context: Natural polymers have attracted a great deal of attention for use as potential carriers in site-specific delivery over past decades. Mucoadhesive microspheres are useful tools for nasal drug delivery.

Objectives: To prepare and evaluate mucoadhesive microspheres as mode for nasal delivery of ondansetron using Caesalpinia pulcherrima galactomannan (CPG).

Materials and methods: Conventional spray-dried CPG nasal microspheres loaded with ondansetron for intranasal drug delivery in order to avoid the first pass metabolism with improved therapeutic efficiency in treatment of nausea and vomiting as an alternative therapy to parenterals. Developed microspheres were evaluated for characteristics like particle size, entrapment efficiency, zeta potential, swelling ability, in-vitro mucoadhesion, in-vitro drug release, DSC, XRD study and histopathological evaluation of tissue. CPG-based ondansetron microspheres were studied in rabbits for screening nasal absorption potential of nasal formulation.

Results: Developed nasal microspheres possess entrapment efficiency of 80–89%, higher mucoadhesion of 72–84% across goat nasal mucosa. In-vivo study showed that microspheres based on mucoadhesive polymer were able to promote quick drug absorption as well as enhanced bioavailability of drug.

Discussion: Histopathological studies evaluated biocompatible and nontoxic nature of CPG in nasal cavity. Developed mucoadhesive microspheres by nasal route showed enhancement of bioavailability as compared to oral route in rabbits.

Conclusion: CPG-based mucoadhesive microspheres can successfully deliver ondansetron intranasally, sustain its effect, avoid first pass effect, an alternative route of administration to injection and thus enhance systemic bioavailability of ondansetron hydrochloride.     

Formulation, and Evaluation of Pentoxifylline-Loaded Poly(��-caprolactone) Microspheres

Pentoxifylline-loaded poly(ε-caprolactone) microspheres were prepared by solvent evaporation technique with different drug to carrier ratio F1 (1:3), F2 (1:4), F3 (1:5) and F4 (1:6). The microspheres were characterized for particle size, scanning electron microscopy, FT-IR study, percentage yield, drug entrapment, stability studies and for in vitro release kinetics. The shape of microspheres was found to be spherical by SEM. The size of microspheres was found to be ranging 59.3±6.3μm to 86.22±4.23 μm. Among the four drug to carrier ratio, F3 (1:5) showed maximum percentage yield of 83.34±2.46% and F2 (1:4) showed highest drug entrapment of 76.92±3.24% w/w. It was found that there was no interaction between drug and polymer by FT-IR study. No appreciable difference was observed in the extent of degradation of product during 60 d in the microspheres, which were stored at various temperatures. In the in vitro release study formulation F2 (1:4) showed 90.34% drug release at 15 h and found to be sustained. The release followed Higuchi kinetics indicating diffusion controlled drug release.     

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.     

Preparation oral levofloxacin colon-specific microspheres delivery: in vitro and in vivo studies

The aim of this study was to prepare levofloxacin-loaded chitosan microspheres and to evaluate their in vitro and in vivo characteristics. Glutaraldehyde-crosslinked microspheres were prepared using a spray-drying method, and characterized in terms of the morphological examination, particle size distribution, entrapment efficiency, drug loading and in vitro release. Pharmacokinetics and colon biodistribution studies were used to evaluate that microspheres have more advantage than the conventional formulations. The surface morphology of the freeze-dried microspheres were smooth, discrete with a regular spherical to near-spherical shape. Size of the microspheres after freeze-drying was 4.96?±?0.76?μm and well-distributed. The zeta potential of microspheres was ?29.3?±?2.1?mV. An average drug loading of 9.3?±?0.4% and encapsulation efficiency of 81.1?±?4.7% of levofloxacin microspheres were obtained with the optimized preparation parameters. The cumulative release rate of levofloxacin microspheres was followed by a sustained release and fitted for classic Higuchi kinetic model. In vivo studies showed that chitosan microspheres are thought to have the potential to maintain levofloxacin concentration within target ranges for a long time, decreasing side effects caused by concentration fluctuation, ensuring the efficiency of treatment and improving patient compliance by reducing dosing frequency. It also does not cause any harmful or toxic effect in colon and rectum as evaluated by histopathologic studies.     

Eudragit RL100 based microspheres for ocular administration of azelastine hydrochloride

In the present study, potential of polymeric microspheres for treatment of allergic conjunctivitis was investigated. Azelastine hydrochloride loaded Eudragit RL100 microspheres were prepared by solvent evaporation technique. The change in drug–polymer ratio on the particle size, zeta potential, entrapment efficiency and in vitro drug release was investigated. As Eudragit concentration ranged from 40 to 80?mg/ml the size range obtained was 4.18–7.36?µm with positive zeta potential. With the increase in drug polymer ratio, the entrapment efficiency was increased with maximum 14.56%. In vitro release studies demonstrated prolonged release of the drug over the period of 6?hr. Scanning electron micrographs showed that microspheres were spherical with distinct solid dense structure. Fourier transform infrared and differential scanning calorimetry studies concluded slight change in peak intensities of drug in microspheres. In vivo studies in rat model indicated that reduction in eosinophil count number was more pronounced in azelastine hydrochloride microspheres than marketed formulation, Azelast®.     

Colon targeted curcumin microspheres laden with ascorbic acid for bioavailability enhancement

An objective of the present study was to prepare colon-specific microspheres of curcumin (CUR) containing ascorbic acid (AA) for improved oral bioavailability. 3² factorial design was used to optimise chitosan microspheres (CSMS) containing CUR and AA. Subsequently, optimised CSMS were coated with Eudragit S-100, for delivery to colon. In vitro drug release, in vivo pharmacokinetics, and organ distribution studies were performed in Albino Wistar rats. Stabilisation of CUR in alkaline pH was successfully guarded by AA to the extent 98.5–100%. Results revealed complete amorphisation/molecular dispersion of CUR. Bioavailability enhancement of CUR and 90% of MS in colon at the end of 8?h in animals, deciphered successful design of colon-specific CUR MS. It can be concluded that AA in MS shielded the degradation of CUR. The developed double coat MS could be considered as a promising colon-targeted system for CUR aiming bioavailability enhancements.     

Spray-dried carbamazepine-loaded chitosan and HPMC microspheres: preparation and characterisation

In this study, the potential of the spray-drying technique for preparing microspheres able to modify the release profile of carbamazepine was investigated. Low-, medium- and high-molecular-weight chitosan and hydroxypropyl methylcellulose (HPMC) in different drug-polymer ratios were used for the preparation of microspheres. The microspheres, characterized by X-ray powder diffractometry (XRD) and differential scanning calorimetry (DSC), were also studied with respect to particle size distribution, drug content and drug release. The results indicated that the entrapment efficiency (EE), as well as carbamazepine release profile, depended on polymeric composition and drug-polymer ratios of the microspheres prepared. The best entrapment efficiencies were obtained when chitosan of low-molecular-weight (CL) or HPMC were used for the microencapsulation. For all types of polymer used, the microspheres with low carbamazepine loading (6.3% w/w) showed better control of drug release than the microspheres with higher drug loadings. The HPMC microspheres showed the slowest carbamazepine release profile with no initial burst effect. Carbamazepine release profiles from ternary systems, carbamazepine-CL-HPMC microspheres, depended mostly on HPMC content and showed similar carbamazepine release profile as CL microspheres when HPMC content was low (9:1 CL-HPMC ratio, w/w). Otherwise, the carbamazepine release from CL-HPMC microspheres was remarkably faster than from either chitosan or HPMC microspheres. The release profile of carbamazepine from the microspheres was highly correlated with the crystalline changes occurring in the matrix.     

Celecoxib Incorporated Chitosan Microspheres: In Vitro and In Vivo Evaluation

Recently, considerable interest has been focussed on the use of biodegradable polymers for specialized applications such as controlled release of drug formulations; meanwhile, microsphere drug delivery systems using various kinds of biodegradable polymers have been studied extensively during the past two decades. In the present investigation, it was aimed to prepare microsphere formulations of celecoxib using a natural polymer, chitosan as a carrier for intra-articular administration to extend the retention of the drug in the knee joint. Microsphere formulations were evaluated in vitro for particle size, entrapment efficiency, surface morphology and in vitro drug release. For in vivo studies, ^99mTechnetium- labeled glutathione was used as a radiopharmaceutical to demonstrate arthritic lesions by gamma scintigraphy. Evaluation of arthritic lesions post therapy in rats showed a significant difference (P<0.05) in the group treated with celecoxib solution compared to the group treated with celecoxib loaded chitosan microspheres.     

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.     

Development and evaluation of sustained-release propranolol wax microspheres

To obtain a sustained-release dosage form with a lack of gastric unwanted effects, wax microspheres containing propranolol (I) were prepared by a congealable dispersion microencapsulation technique. The effects of the process variables; type of wax, speed of emulsification, amount of drug loaded, type and amount of emulsifier, were studied on the entrapment efficiency, angle of repose, dissolution efficiency (DE), in-vitro drug release and mean particle size of (I) microspheres, by a factorial design. The results showed that changes in the amount of emulsifier (Tween), 0.04% and 0.08%, the type of Tween (80 and 20) and the wax type; beeswax or ceresine, caused a significant decrease in the entrapment efficiency. All the variables had an effect on the angle of repose and particle size of the (I) microspheres. The only significant parameter affecting the DE was the nature of the wax. The drug release in pH 6.8 was affected by all the variables except the amount of emulsifier. The formulation with a 0.25:4 ratio of drug:ceresine wax and 0.04% of Tween 80 in 600 rpm emulsification speed showed a suitable multiparticulate delivery system for the retarded dissolution of entrapped active ingredients, allowing absorption only in the intestinal tract.     

An Improvement of the Efficacy of Moxifloxacin HCl for the Treatment of Bacterial Keratitis by the Formulation of Ocular Mucoadhesive Microspheres

The aim of this study was to prepare novel ocular mucoadhesive microspheres of Moxifloxacin HCl to increase its residence time on the ocular surface and to enhance its therapeutic efficacy in ocular bacterial keratitis. Microspheres were fabricated with different grades of Methocel and Sodium CMC as polymers. Microspheres were evaluated for their particle size, morphology, encapsulation efficiency, mucoadhesion, antimicrobial efficacy, and in vitro drug release studies. In vivo studies were carried out for the promising formulation on eyes of albino rabbits by inducing bacterial keratitis. A sterile microspheres suspension in light mineral oil was applied to infected eyes twice a day. A marketed conventional eye drop was used as a positive control. Eyes were examined daily for improvement of clinical signs of bacterial keratitis by an ophthalmologist. The average particle size of microspheres was found to be less than 80 μm. Methocel microspheres were found to have a smoother surface than Sodium CMC. Entrapment efficiency was enhanced with an increased polymer concentration and viscosity. The formulation containing Methocel K100M with a drug: polymer ratio of 1:2 exerted longer corneal and conjunctival mucoadhesion time of 8.45±0.15 h and 9.40±0.53 h respectively. In vitro release of Moxifloxacin HCl from microspheres was retarded with increased viscosity and concentration of polymers, and was controlled by diffusion as well as polymer relaxation. All formulations showed comparable antimicrobial activity in comparison with conventional marketed eye drops. The formulation containing Methocel K100M with a drug: polymer ratio of 1:2 was found to be a promising formulation and was used for the in vivo studies. The in vivo studies revealed that microspheres demonstrated significantly lower clinical scores and reduced the total duration of therapy than the marketed Moxifloxacin HCl eye drops. In vitro and in vivo studies showed that ocular mucoadhesive microspheres of Moxifloxacin HCl were found to have an improved efficacy in the treatment of ocular bacterial keratitis in comparison with the marketed formulation.     

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.     

Effect of Formulation and Processing Variables on the Characteristics of Tolmetin Microspheres Prepared by Double Emulsion Solvent Diffusion Method

The aim of this study was to evaluate microencapsulated controlled release preparations of tolmetin sodium using ethylcellulose as a retardant material. Microspheres were prepared by using water-in-oil-in-oil (W/O₁/O₂) double-emulsion solvent diffusion method, using different ratios of ethylcellulose to tolmetin sodium. Span 80 was used as the droplet stabilizer and n-hexane was added to harden the microspheres. The prepared microspheres were characterized for their micromeritic properties, drug content, loading efficiency, production yield, and particle size. Fourier transform infrared spectroscopy, differential scanning calorimetry, X-ray powder diffractometry and scanning electron microscopy were used to characterize microparticles. The in vitro release studies were performed in pH 1.2 and 7.4. The prepared microspheres were spherical in shape. The drug-loaded microspheres showed near to the theoretical of entrapment and release was extended up to 24. The X-ray diffractogram and differential scanning thermographs showed amorphous state of the drug in the microspheres. It was shown that the drug: polymer ratio, stirring rate, volume of dispersing medium and surfactant influenced the drug loading, particle size and drug release behavior of the formed microparticles. The results showed that, generally, an increase in the ratio of drug: polymer (0.5:1) resulted in a reduction in the release rate of the drug which may be attributed to the hydrophobic nature of the polymer. The in vitro release profile could be modified by changing various processing and formulation parameters to give a controlled release of drug from the microparticules. The release of tolmetin was influenced by the drug to polymer ratio and particle size and was found to be diffusion and erosion controlled. The best-fit release kinetic was achieved with Peppas model.