Interpenetrating polymer network (IPN) hydrogel microspheres for oral controlled release application

Interpenetrating polymer network (IPN) hydrogel microspheres of sodium carboxymethyl cellulose (NaCMC) and poly(vinyl alcohol) (PVA) were prepared by water-in-oil (w/o) emulsion crosslinking method for oral controlled release delivery of a non-steroidal anti-inflammatory drug, diclofenac sodium (DS). The microspheres were prepared with various ratios of NaCMC to PVA, % drug loading and extent of crosslinking density at a fixed polymer weight. The prepared microspheres with loose and rigid surfaces were evidenced by scanning electron microscope (SEM). Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) analysis confirmed the IPN formation. Differential scanning calorimetry (DSC) study was performed to understand the dispersion nature of drug after encapsulation. The in vitro drug release study was extensively evaluated depending on the process variables in both acid and alkaline media. All the formulations exhibited satisfactory physicochemical and in vitro release characteristics. Release data indicated a non-Fickian trend of drug release from the formulations. Based on the results of this study suggest that DS loaded IPN microspheres were suitable for oral controlled release application.     

Synthesis and characterization of semi-interpenetrating polymer network microspheres of acrylamide grafted dextran and chitosan for controlled release of acyclovir

Semi-interpenetrating polymer network (IPN) microspheres of acrylamide grafted on dextran (AAm-g-Dex) and chitosan (CS) were prepared by emulsion-crosslinking method using glutaraldehyde (GA) as a crosslinker. The grafting efficiency was found to be 94%. Acyclovir, an antiviral drug with limited water solubility, was successfully encapsulated into IPN microspheres by varying the ratio of AAm-g-Dex and CS, % drug loading and amount of GA. Microspheres were characterized by FT-IR spectroscopy to assess the formation of IPN structure and to confirm the absence of chemical interactions between drug, polymer and crosslinking agent. Particle size was measured using laser light scattering technique. Microspheres with average particle sizes in the range of 265–388 μm were obtained. Differential scanning calorimetry (DSC) and X-ray diffraction (X-RD) studies were performed to understand the crystalline nature of drug after encapsulation into IPN microspheres. Acyclovir encapsulation of up to 79.6% was achieved as measured by UV spectroscopy. Both equilibrium and dynamic swelling studies were performed in 0.1 N HCl. Diffusion coefficients (D) and diffusional exponents (n) for water transport were determined using an empirical equation. In vitro release studies indicated the dependence of drug release rates on both the extent of crosslinking and amount of AAm-g-Dex used in preparing microspheres; the slow release was extended up to 12 h. The release rates were fitted to an empirical equation to compute the diffusional exponent (n), which indicated non-Fickian trend for the release of acyclovir.     

Novel interpenetrating polymer network microspheres of chitosan and methylcellulose for controlled release of theophylline

Interpenetrating polymer network (IPN) microspheres of chitosan (CS) and methylcellulose (MC) were prepared by emulsion-crosslinking in the presence of glutaraldehyde (GA) as a crosslinker. Theophylline (THP), an antiasthmatic drug was encapsulated into IPN microspheres under varying ratios of MC and CS, % drug loading and amount of GA added. IPNs have shown better mechanical properties than pure CS. Cross-link density of the matrices was significantly affected by the amount of GA and MC. Microspheres were characterized by Fourier transform infrared (FTIR) spectroscopy to assess the formation of IPN structure and to confirm the absence of chemical interactions between drug, polymer and crosslinking agent. Particle size was measured by laser light scattering technique. Microspheres with the average particle sizes ranging from 119 to 318 μm were produced. Differential scanning calorimetry (DSC) and X-ray diffraction (X-RD) studies were performed to understand the crystalline nature of drug after encapsulation into IPN microspheres. Theophylline encapsulation of up to 82% was achieved as measured by UV spectrometer. Equilibrium swelling was performed in distilled water. In vitro release studies were performed in both 0.1 N HCl and pH 7.4 buffer solutions. These data indicated a dependence of drug release on the extent of crosslinking and amount of MC added during the preparation of microspheres. The release was extended up to 12 h and release rates were fitted to an empirical equation to compute the diffusional parameters, which indicated a slight deviation from the Fickian trend for the release of theophylline.     

An Epichlorohydrin-Crosslinked Semi-Interpenetrating GG-PEO Network as a Xerogel Matrix for Sustained Release of Sulpiride

The current study involved the development of a novel sustained release crosslinked semi-IPN xerogel matrix tablet prepared by chemical crosslinking of poly(ethylene) oxide (PEO) and gellan gum (GG) employing epichlorohydrin (EPI) as crosslinker. A Box–Behnken design was employed for the statistical optimization of the matrix system to ascertain the ideal combination of native polymeric and crosslinking agents. Characterization studies were performed by employing standard polymer characterization techniques such as Fourier transform infrared spectrometry, differential scanning calorimetry, and scanning electron microscopy. Formulated matrix tablets displayed zero-order release kinetics, extending over 24 h. The mechanism of drug release was primarily by swelling and surface erosion. Crosslinked semi-IPN xerogel matrix tablets were compared to non-crosslinked polymer blends; results from the study conducted showed that the physiochemical properties of the PEO and GG were sufficiently modified to allow for sustained release of sulpiride with a 100% drug release at 24 h in a controlled manner as compared to non-crosslinked formulations which displayed further release beyond the test period. Crosslinked formulations displayed water uptake between 450 and 500% indicating a controlled rate of swelling and erosion allowing for sustained release. Surface morphology of the crosslinked system depicted a porous structure formed by interpenetrating networks of polymers, allowing for a greater degree of controlled penetration into the system affording it the ability to sustain drug release. Therefore, conclusively, based on the study performed, crosslinked PEO-GG allows for the sustained release of sulpiride from a hydrophilic semi-IPN xerogel matrix system.KEY WORDS: epichlorohydrin, matrix tablet, semi-interpenetrating polymer network, sustained release, sulpiride     

Evaluation of orntide microspheres in a rat animal model and correlation to in vitro release profiles

Orntide acetate, a novel luteinizing hormone-releasing hormone (LHRH) antagonist, was prepared and evaluated in vivo in 30-day and 120-day sustained delivery formulations using a rat animal model. Orntide poly(d,l- lactide-co-glycolide) (PLGA) and poly(d,l- lactide) (PLA) microspheres were prepared by a dispersion method and administered subcutaneously in a liquid vehicle to rats at 2.2 mg Orntide/kg of body weight (30-day forms) or 8.8 mg Orntide/kg (120-day forms). Serum levels of Orntide and testosterone were monitored by radioimmunoassays, and a dose-response study at 4 closes (3, 2.25, 1.5, and 1.75 mg Orntide/kg) was conducted to determine the effective dose of Orntide. Microspheres with diameters between 3.9 and 14 μ were prepared. The onset and duration of testosterone suppression varied for different microsphere formulations and were influenced both by polymer properties and by microsphere characteristics. Microspheres prepared with 50∶50 and 75∶25 copolymers effectively sustained peptide release for 14 to 28 days, whereas an 85∶15 copolymer and the PLA microspheres extended the pharmacological response for more than 120 days. Increase in drug load generally accelerated peptide release from the microspheres, resulting in higher initial serum levels of Orntide and shorter duration of the release: In general, apparent release was faster in vivo than under in vitro conditions. Orntide microspheres effectively suppressed testosterone in rats, providing rapid onset of release and extended periods of chemical castration. Testosterone suppression occurred immediately after microsphere administration without the initial elevation seen with LHRH superagonists.     

Characterization of 5-fluorouracil microspheres for colonic delivery

The purpose of this investigation was to prepare and evaluate the colon-specific microspheres of 5-fluorouracil for the treatment of colon cancer. Core microspheres of alginate were prepared by the modified emulsification method in liquid paraffin and by cross-linking with calcium chloride. The core microspheres were coated with Eudragit S-100 by the solvent evaporation technique to prevent drug release in the stomach and small intestine. The microspheres were characterized by shape, size, surface morphology, size distribution, incorporation efficiency, and in vitro drug release studies. The outer surfaces of the core and coated microspheres, which were spherical in shape, were rough and smooth, respectively. The size of the core microspheres ranged from 22 to 55 μm, and the size of the coated microspheres ranged from 103 to 185 μm. The core microspheres sustained the drug release for 10 hours. The release studies of coated microspheres were performed in a pH progression medium mimicking the conditions of the gastrointestinal tract. Release was sustained for up to 20 hours in formulations with core microspheres to a Eudragit S-100 coat ratio of 1∶7, and there were no changes in the size, shape, drug content, differential scanning calorimetry thermogram, and in vitro drug release after storage at 40°C/75% relative humidity for 6 months.     

Osmotic flow through asymmetric membrane: A means for controlled delivery of drugs with varying solubility

A nondisintegrating, controlled release, asymmetric membrane capsular system of flurbiprofen was developed and evaluated for controlled release of the drug to overcome some of its side effects. Asymmetric membrane capsules were prepared using fabricated glass mold pins by phase inversion process. The effect of different formulation variables was studied based on 2³ factorial design; namely, level of osmogen, membrane thickness, and level of pore former. Effects of polymer diffusibility and varying osmotic pressure on drug release were also studied. Membrane characterization by scanning electron microscopy showed an outer dense region with less pores and an inner porous region for the prepared asymmetric membrane. Differential scanning calorimetry studies showed no incompatibility between the drug and the excipients used in the study. In vitro release studies for all the prepared formulations were done (n=6). Statistical test (Dunnett multiple comparison test) was applied for in vitro drug release atP>.05. The best formulation closely corresponded to the extra design checkpoint formulation by a similarity (f2) value of 92.94. The drug release was independent of pH but dependent on the osmotic pressure of the dissolution medium. The release kinetics followed the Higuchi model and the mechanism of release was Fickian diffusion. Published: July 7, 2006     

Investigations on the Physical Structure and the Mechanism of Drug Release from an Enteric Matrix Microspheres with a Near-Zero-Order Release Kinetics Using SEM and Quantitative FTIR

The objectives of this study were to evaluate the physical structure and the release mechanisms of theophylline microspheres made of Eudragit S 100 polymer as an enteric polymer, combined with a nonerodible polymer, Eudragit RL 100. In the preparation process, polymer combinations (1:1) were dissolved in an organic solvent mixture composed of acetone and methanol at a specific ratio containing a theoretical drug loading of approximately 15%. Two microsphere formulations (LS1 and LS2) were prepared at two different total polymer concentrations (10% in LS1 and 12.7% in LS2). Dissolution studies were carried out using US Pharmacopeia Dissolution Apparatus II in an acidic medium for 8 h and in an acidic medium (2 h) followed by a slightly basic-buffered medium for 10 h. Both LS1 and LS2 microsphere formulations produced particles that were spherical in shape and had very narrow size distributions with one size fraction comprising 70–80% of the yield. Scanning electron microscopy and quantitative Fourier transform infrared were used for microsphere physical structure evaluation. Except for the absence of drug crystals, photomicrographs of both LS microspheres after dissolution in pH 1.2 and 7.2 buffer solutions were similar to those before dissolution. Dissolution results indicated the ability of LS microspheres to minimize drug release during the acid stage. However, in the slightly basic medium that followed the acidic stage, the drug release was sustained and controlled in its kinetics and data fitted to Peppas equation indicated a case II transport suggesting that the drug release is mainly through swelling/erosion mechanism.     

Albumin microspheres as carriers for the antiarthritic drug celecoxib

The present study investigates the preparation of celecoxib-loaded albumin microspheres and the biodistribution of technetium-99m (^99mTc)-labeled celecoxib as well as its microspheres after intravenous administration. Microspheres were prepared using a natural polymer BSA using emulsification chemical cross-linking method. The prepared microspheres were characterized for entrapment efficiency, particle size, and in vitro drug release. Surface morphology was studied by scanning electron microscopy. Biodistribution studies were performed by radiolabeling celecoxib (CS) and its microspheres (CMS) using^99mTc and injecting arthritic rats intravenously. The geometric mean diameter of the microspheres was found to be 5.46 μm. In vitro release studies indicated that the microspheres sustained the release of the drug for }6 days. Radioactivity measured in different organs after intravenous administration of celecoxib solution showed a significant amount of radioactivity in the liver and spleen. In case of celecoxib-loaded microspheres, a significant amount of radioactivity accumulated in the lungs. No significant difference (P>.1) in the radioactivity was observed between the inflamed joint and the noninflamed joint following intravenous injection of^99mTc-CS. However, in case of the microspheres (CMS), the radioactivity present in the inflamed joint was 2.5-fold higher than in the noninflamed joint. The blood kinetic studies revealed that celecoxib-loaded albumin microspheres exhibited prolonged circulation than the celecoxib solution.     

Process and formulation variables in the preparation of injectable and biodegradable magnetic microspheres

The aim of this study was to prepare biodegradable sustained release magnetite microspheres sized between 1 to 2 μm. The microspheres with or without magnetic materials were prepared by a W/O/W double emulsion solvent evaporation technique using poly(lactide-co-glycolide) (PLGA) as the biodegradable matrix forming polymer. Effects of manufacturing and formulation variables on particle size were investigated with non-magnetic microspheres. Microsphere size could be controlled by modification of homogenization speed, PLGA concentration in the oil phase, oil phase volume, solvent composition, and polyvinyl alcohol (PVA) concentration in the outer water phase. Most influential were the agitation velocity and all parameters that influence the kinematic viscosity of oil and outer water phase, specifically the type and concentration of the oil phase. The magnetic component yielding homogeneous magnetic microspheres consisted of magnetite nanoparticles of 8 nm diameter stabilized with a polyethylene glycole/polyacrylic acid (PEG/PAA) coating and a saturation magnetization of 47.8 emu/g. Non-magnetic and magnetic microspheres had very similar size, morphology, and size distribution, as shown by scanning electron microscopy. The optimized conditions yielded microspheres with 13.7 weight% of magnetite and an average diameter of 1.37 μm. Such biodegradable magnetic microspheres seem appropriate for vascular administration followed by magnetic drug targeting.     

尺寸均一的壳聚糖微球的制备及其作为胰岛素控释载体的研究

采用新型微孔膜乳化技术制备了载胰岛素的壳聚糖微球。研究表明,要制备粒径均一的壳聚糖微球,必须将亲水性膜修饰成疏水性;制得的微球粒径和所采用的膜孔径之间存在很好的线性关系,使得微球粒径可控;以胰岛素为模型药物,主要考察了交联剂用量和交联时间对微球表面形态、药物包埋率和微球体外释药特性的影响。结果表明当氨基与醛基的摩尔比为1∶0.7、交联时间为1h时,所得载药微球的包埋率最高,随着戊二醛用量的增加和交联时间的延长,药物体外释放速率减慢。     

Synthesis and characterization of chitosan-based pH-sensitive semi-interpenetrating network microspheres for controlled release of diclofenac sodium

pH-Sensitive semi-interpenetrating networks (IPNs) based on chitosan (Cs) and acrylamide-grafted hydroxyethylcellulose (AAm-g-HEC) were prepared in the form of microspheres (MPs) by emulsion-crosslinking technique using glutaraldehyde (GA) as a crosslinker. Diclofenac sodium (DS) drug was successfully encapsulated into IPN microspheres by varying the ratio of Cs and AAm-g-HEC, % drug loading, and amount of GA. DS encapsulation of up to 83% was obtained as measured by UV spectroscopy. MPs with average particle sizes in the range of 188-310 μm were obtained. MPs were characterized by Fourier transform infrared spectroscopy (FTIR), Scanning electron microscopy (SEM), and Differential scanning calorimetry (DSC). Diffusion coefficients (D) of water transport through the microspheres were determined using an empirical equation. In vitro release of DS from these matrices has been investigated in pH 1.2 and 7.4 media.     

一种白细胞介素 -12 缓释微球制备及体外表征

目的:开发一种白细胞介素-12(IL-12)长效缓释微球剂型。方法:采用水包油-油包固(S/O/W)法制备了白介素-12因子多糖微粒的聚乳酸-聚羟基乙酸共聚物(PLGA-PLA)微球,研究了微球的表面形态和粒径大小,并且运用ELISA方法考察了微球的体外释放效果和免疫活性。结果:本方法制备的白介素-12因子微球光滑圆整,体外缓释达45天,累积释放率近90%。结论:本方法制备的白介素-12因子微球,不仅具有有效地保护IL-12蛋白活性,同时实现长效缓释的目标,是一种可行的IL-12缓释方案。     

Spray-dried poly(D,L-lactide) microspheres containing carboplatin for veterinary use: In vitro and in vivo studies

The aim of this study was the development of a veterinary dosage form constituted by injectable biodegradable microspheres designed for the subcutaneous release of carboplatin, a chemotherapeutic drug. Poly(D,L-lactide) (PDLLA) microspheres were prepared by an emulsification/spray-drying method, using the drug-to-polymer weight ratios 1∶9 and 1∶5; blank microspheres (1% w/v) were prepared as a comparison. Microparticles were characterized in terms of morphology, encapsulation efficiency, and in vitro drug release behavior. In vivo tests were conducted on rats by subcutaneous injection of microsphere aqueous suspensions. Levels of carboplatin were evaluated both in the skin and in serum. The microparticles obtained had a spherical shape; particle size ranged from 5 to 7 μm, dependent on drug loading. Microspheres were able to control the in vitro release of the drug: approximately 90% to 100% of the carboplatin was released over 30 days. In vivo results showed that the microspheres were able to release high drug amounts locally, and sustained serum levels of drug were also achieved. Based on these results, carboplatin-loaded PDLLA microspheres may be useful for local delivery of the antineoplastic drug to the tumor, avoiding tumor recurrence in small animals, and may decrease the formation of distant metastases. Published: September 20, 2005     

Mucoadhesive vaginal tablets as veterinary delivery system for the controlled release of an antimicrobial drug,acriflavine

The aim of the study was the development of mucoadhesive vaginal tablets designed for the local controlled release of acriflavine, an antimicrobial drug used as a model. The tablets were prepared using drug-loaded chitosan microspheres and additional excipients (methylcellulose, sodium alginate, sodium carboxymethylcellulose, or Carbopol 974). The microspheres were prepared by a spray-drying method, using the drug to polymer weight ratios 1:1 and 1:2 and were characterized in terms of morphology, encapsulation efficiency, and in vitro release behavior, as MIC (Minimum Inhibitory Concentration), MBC (Minimum Bacterial Concentration), and killing time (KT). The tablets were prepared by direct compression, characterized by in vitro drug release and in vitro mucoadhesive tests. The microparticles have sizes of 4 to 12 microm; the mean encapsulation yields are about 90%. Acriflavine, encapsulated into the polymer, maintains its antibacterial activity; killing time of the encapsulated drug is similar to that of the free drug. In vitro release profiles of tablets show differences depending on the excipient used. In particular Carbopol 974, which is highly cross-linked, is able to determine a drug-controlled release from the matrix tablets for more than 8 hours. The in vitro adhesion tests, carried out on the same formulation, show a good adhesive behavior. The formulation containing microspheres with drug to polymer weight ratios of 1:1 and Carbopol 974 is characterized by the best release behavior and shows good mucoadhesive properties. These preliminary data indicate that this formulation can be proposed as a mucoadhesive vaginal delivery system for the controlled release of acriflavine.     

Ethylcellulose-Based Matrix-Type Microspheres: Influence of Plasticizer RATIO as Pore-Forming Agent

In this study, ethylcellulose (EC)-based microsphere formulations were prepared without and with triethyl citrate (TEC) content of 10% and 30% by water-in-oil emulsion-solvent evaporation technique. Diltiazem hydrochloride (DH) was chosen as a hydrophilic model drug and used at different drug/polymer ratios in the microspheres. The aim of the work was to evaluate the influence of plasticizer ratio on the drug release rate and physicochemical characteristics of EC-based matrix-type microspheres. The resulting microspheres were evaluated for encapsulation efficiency, particle size and size distribution, surface morphology, total pore volume, thermal characteristics, drug release rates, and release mechanism. Results indicated that the physicochemical properties of microspheres were strongly affected by the drug/polymer ratio investigated and the concentration of TEC used in the production technique. The surface morphology and pore volume of microspheres significantly varied based on the plasticizer content in the formulation. DH release rate from EC-based matrix-type microspheres can be controlled by varying the DH to polymer and plasticizer ratios. Glass transition temperature values tended to decrease in conjunction with increasing amounts of TEC. Consequently, the various characteristics of the EC microspheres could be modified based on the plasticized ratio of TEC.     

Synthesis and properties of thermo- and pH-sensitive poly(N-isopropylacrylamide)/polyaspartic acid IPN hydrogels

Various interpenetrating polymer network (IPN) hydrogels with sensitivity to temperature and pH were prepared by introducing the pH-sensitive polymer polyaspartic acid (PASP) hydrogel, into the poly(N-isopropylacrylamide) (PNIPAAm) hydrogel system for the purpose of improving its response rate to temperature. The morphologies and thermal behavior of the prepared IPN hydrogels were studied by both scanning electron microscopy (SEM) and differential scanning calorimetry (DSC). The IPN hydrogels showed a large and uneven porous network structure, without showing the common PNIPAAm hydrogel structure. The paper moreover studied their swelling properties, such as temperature dependence of equilibrium swelling ratio, shrinking kinetics, re-swelling kinetics and oscillatory swelling behavior in water. The swelling experiment results revealed that IPN hydrogels exhibited much faster shrinking and re-swelling in function of the composition ratio of the two network components. These fast responsive hydrogels foster potential applications in biomedical and biotechnology fields.     

Sustained release of the antitumor drug paclitaxel from poly(3-hydroxybutyrate)-based microspheres

The development of sustained release formulations based on biodegradable polymers is a promising trend in modern pharmacology. Polyhydroxyalkanoates (PHA) attract increasing attention due to their biodegradability and high biocompatibility, which make them suitable for the development of novel drug dosage forms. We have produced poly(3-hydroxybutyrate) (PHB)-based microspheres loaded with the antitumor drug paclitaxel and investigated morphology, drug release kinetics and the effect of these microspheres on tumor cells in vitro. The data on the kinetics of drug release, biocompatibility and biological activity of the biopolymer microspheres in vitro have demonstrated that the studied system of prolonged drug release had lower toxicity and higher efficiency compared to the traditional dosage forms of paclitaxel.     

Preparation and characterization of temperature-sensitive poly(N-isopropylacrylamide)-b-poly(D,L-lactide) microspheres for protein delivery

Temperature-sensitive diblock copolymers, poly(N-isopropylacrylamide)-b-poly(D,L-lactide) (PNIPAAm-b-PLA) with different PNIPAAm contents were synthesized and utilized to fabricate microspheres containing bovine serum albumin (BSA, as a model protein) by a water-in-oil-in-water double emulsion solvent evaporation process. XPS analysis showed that PNIPAAm was a dominant component of the microspheres surface. BSA was well entrapped within the microspheres, and more than 90% encapsulation efficiency was achieved. The in vitro degradation behavior of microspheres was investigated using SEM, NMR, FTIR, and GPC. It was found that the microspheres were erodible, and polymer degradation occurred in the PLA block. Degradation of PLA was completed after 5 months incubation in PBS (pH 7.4) at 37 degrees C. A PVA concentration of 0.2% (w/v) in the internal aqueous phase yielded the microspheres with an interconnected porous structure, resulting in fast matrix erosion and sustained BSA release. However, 0.05% PVA produced the microspheres with a multivesicular internal structure wrapped with a dense skin layer, resulting in lower erosion rate and a biphasic release pattern of BSA that was characterized with an initial burst followed by a nonrelease phase. The microspheres made from PNIPAAm-b-PLA with a higher portion of PNIPAAm provided faster BSA release. In addition, BSA release from the microspheres responded to the external temperature changes. BSA release was slower at 37 degrees C (above the LCST) than at a temperature below the LCST. The microspheres fabricated with PNIPAAm-b-PLA having a 1:5 molar ratio of PNIPAAm to PLA and 0.2% (w/v) PVA in the internal aqueous phase provided a sustained release of BSA over 3 weeks in PBS (pH 7.4) at 37 degrees C.     

Eudragit-coated pectin microspheres of 5-fluorouracil for colon targeting

An objective of the present investigation was to prepare and evaluate Eudragit-coated pectin microspheres for colon targeting of 5-fluorouracil (FU). Pectin microspheres were prepared by emulsion dehydration method using different ratios of FU and pectin (1:3 to 1:6), stirring speeds (500–2000 rpm) and emulsifier concentrations (0.75%–1.5% wt/vol). The yield of preparation and the encapsulation efficiencies were high for all pectin microspheres. Microspheres prepared by using drug:polymer ratio 1:4, stirring speed 1000 rpm, and 1.25% wt/vol concentration of emulsifying agent were selected as an optimized formulation. Eudragit-coating of pectin microspheres was performed by oil-in-oil solvent evaporation method using coat: core ratio (5:1). Pectin microspheres and Eudragit-coated pectin microspheres were evaluated for surface morphology, particle size and size distribution, swellability, percentage drug entrapment, and in vitro drug release in simulated gastrointestinal fluids (SGF). The in vitro drug release study of optimized formulation was also performed in simulated colonic fluid in the presence of 2% rat cecal content. Organ distribution study in albino rats was performed to establish the targeting potential of optimized formulation in the colon. The release profile of FU from Eudragit-coated pectin microspheres was pH dependent. In acidic medium, the release rate was much slower; however, the drug was released quickly at pH 7.4. It is concluded from the present investigation that Eudragit-coated pectin microspheres are promising controlled release carriers for colon-targeted delivery of FU. Published: February 16, 2007