Improved bioavailability of orally delivered insulin using Eudragit-L30D coated PLGA microparticles

Large porous microparticles of PLGA entrapping insulin were prepared by solvent evaporation method and evaluated in diabetes induced rat for its efficacy in maintaining blood sugar level from a single oral dose. Incorporation of Eudragit L30D (0.03% w/v) in the external aqueous phase resulted in formation of pH responsive enteric coated polymer particles which release most of the entrapped insulin in alkaline pH. At acidic pH, release of insulin from uncoated PLGA microparticles and Eudragit L30D coated PLGA microparticles was 31.62?±?1.8% and 17.5?±?1.29%, respectively, for initial 30 min. However, in 24 h, in vitro released insulin from uncoated PLGA and Eudragit coated particles was 96.29?±?1.01% and 88.30?±?1%, respectively. Released insulin from composite polymer particles were mostly in monomer form without aggregation and was stable for a month at 37°C. Oral administration of insulin loaded PLGA (50 : 50) and Eudragit L30D coated PLGA (50 : 50) microparticles (equivalent to 25 IU insulin/kg of animal weight) in alloxan induced diabetic rats resulted in 37.3?±?11% and 62.7?±?3.8% reduction in blood glucose level, respectively, in 2 h. This effect continued up to 24 h in the case of Eudragit L30D coated PLGA microparticles. Results demonstrate that use of stabilizers during PLGA particle formulation, large porous particle for quick release of insulin and coating with Eudragit L30D resulted in a novel oral formulation for once a day delivery of insulin.     

Development of pH- and time-dependent oral microparticles to optimize budesonide delivery to ileum and colon

A microparticulate system consisting of non-enzymatically degrading poly(dl-lactide-co-glycolide) (PLGA) core and delivering budesonide site specifically to distal ileum and colon was developed. Budesonide-loaded microparticles were fabricated using solvent evaporation technique and formulation variables studied included different molecular weight grades of PLGA polymer as well as concentration of polymer, surfactant and drug. Eudragit S-100, an enteric polymer, was then used to form a coating on the surface of budesonide-loaded PLGA microparticles for site specific delivery to the distal ileum and colon. Budesonide-loaded PLGA microparticles prepared from various formulation parameters showed mean encapsulation efficiencies ranging between 50% and 85% and mean particle size ranging between 10 and 35mum. In vitro release kinetics studies showed a biphasic release pattern with an initial higher release followed by a slower drug release. Increasing polymer and surfactant concentrations exhibited sharply contrasting drug release profiles, with increasing polymer concentrations resulting in a lower drug release and vice versa. The budesonide-loaded PLGA microparticles coated with Eudragit S-100 coating showed a decrease in entrapment efficiency with an accelerated in vitro drug release. Moreover, complete retardation of drug release in an acidic pH, and, once the coating layer of enteric polymer was dissolved at higher pH (7.4 and 6.8), a controlled release of the drug from the microparticles were observed. From the results of this investigation, the application of double microencapsulation technique employing PLGA matrix and Eudragit S-100 coating shows promise for site specific and controlled delivery of budesonide in Crohn's disease.     

In vitro release and in vivo absorption in beagle dogs of meloxicam from Eudragit FS 30 D-coated pellets

The objective of this study was to develop meloxicam-loaded colon-specific pellets coated with Eudragit FS 30 D and further evaluate their in vitro release and in vivo absorption in beagle dogs. Meloxicam-loaded cores (drug loading, 4.8%, w/w) were prepared by layering drug-binder (HPMC)-solubilizer (beta-cyclodextrin) solution onto nonpareils (710-850 microm) and then coated with a copolymer of methyl acrylate, methyl methacrylate and methacrylic acid (Eudragit FS 30 D). The obtained pellets with 15% (w/w) coating level had a spherical form and a smooth surface with coating thickness approximately 28 microm. The in vitro drug release from the pellets was pH-dependent with sufficient gastric resistance (pH 1.2: no release; pH 6.8: 6%; pH 7.0: 52%; pH 7.2: 100%; pH 7.4: 100%, after 3 h incubation). In vivo study was carried out using pentagastrin-pretreated beagle dogs. The onset of meloxicam absorption from the coated pellets with 15% (w/w) Eudragit FS 30 D (3.0+/-0.8 h) was significantly delayed (p<0.05) compared to that from the uncoated drug-layered cores (0.6+/-0.3 h). The area under the meloxicam plasma concentration-time curve (AUC(0-->96)(h) was not significantly different between the two preparations (p>0.05), although AUC(0-->96)(h) obtained after oral administration of coated pellets (142.5+/-59.6 microg h/ml) was lower than that obtained after administration of uncoated drug-layered cores (180.8+/-61.9 microg h/ml). These results suggested that meloxicam could be delivered to the colon with 15% (w/w) coating level of Eudragit FS 30 D and this polymer coating had no significant influence on the relative bioavailability of meloxicam of the pellets.     

Influence of an enteric polymer on drug release rates of theophylline from pellets coated with Eudragit RS 30D

The purpose of this research study was to investigate the influence of an enteric polymer on the drug release properties of theophylline pellets coated with Eudragit RS 30D. Theophylline pellets were coated with aqueous colloidal dispersions of Eudragit RS 30D containing various amounts of Eudragit L 100-55. The effect of storage conditions on the release of drug from coated pellets was determined as a function of the pH of the dissolution medium. The results from the dissolution study showed significant changes in the dissolution rate of theophylline from pellets coated with Eudragit RS 30D when cured at 40 degrees C for 4 days. No change in the drug release rate was observed when Eudragit L100-55 was present in the Eudragit RS 30D dispersion. Increasing the ratio of Eudragit L100-55 to Eudragit RS 30D resulted in faster drug release rates from the coated pellets. An increase in the pH of the dissolution medium was found to enhance drug release from the pellets coated with Eudragit RS 30D containing Eudragit L 100-55. Theophylline pellets when coated with Eudragit RS 30D containing the enteric polymer Eudragit L100-55 demonstrated no aging effects when stored at elevated temperatures. The overcoating of the pellets with Eudragit RD 100 did not affect the drug release profiles and prevented the particles from agglomerating during curing and storage.     

Effects of alginate coated on PLGA microspheres for delivery tetracycline hydrochloride to periodontal pockets

The effects of alginate coated on tetracycline (Tc) loaded poly (D, L-lactic-co-glycolic acid) (PLGA) microspheres fabricated by double emulsion solvent evaporation technique for local delivery to periodontal pocket were investigated. Alginate coated PLGA microspheres showed smoother surface but enlarged their particle sizes compared with those of uncoated ones. In addition, alginate coated microspheres enhanced Tc encapsulation efficiency (E.E.) from 11.5 +/- 0.5% of uncoated ones to 17.9 +/- 0.5%. Moreover, all of the coated PLGA microspheres even fabricated at different conditions could prolong Tc release from 9-12 days with 50% or higher in cumulative release of Tc compared with those of uncoated ones. The swelling ratios of PLGA microspheres for alginate coated or uncoated ones, one of the possible mechanisms for enhancing Tc release for the coated ones, were measured. The results showed that 20% or higher in swelling ratio for the coated microspheres at the earlier stage of hydration (e.g. < or = 24 h) could be an important factor to result in high Tc release compared to the uncoated ones. In conclusion, alginate coated Tc loaded PLGA microspheres could enhance Tc delivery to periodontal pocket by enhancing drug encapsulated efficiency, released quantities and sustained release period compared with uncoated ones.     

Enteric coated HPMC capsules designed to achieve intestinal targeting.

The enteric coating of HPMC capsules containing paracetamol was investigated. Two enteric polymers, Eudragit L 30 D-55 and Eudragit FS 30 D were studied, which are designed to achieve enteric properties and colonic release, respectively. The capsules were coated in an Accela Cota 10, and, as shown by optical microscopy, resulted in capsules with a uniform coating. Scanning electron microscopy of the surface of the capsules illustrate that, in contrast to gelatin, HPMC has a rough surface, which provides for good adhesion to the coating. Dissolution studies demonstrated that capsules coated with Eudragit L 30 D-55 were gastro resistant for 2 h at pH 1.2 and capsules coated with Eudragit FS 30 D were resistant for a further 1 h at pH 6.8. The product visualisation technique of gamma scintigraphy was used to establish the in vivo disintegration properties of capsules coated with 8 mg cm(-2) Eudragit L 30 D-55 and 6 mg cm(-2) Eudragit FS 30 D. For HPMC units coated with Eudragit L 30 D-55, complete disintegration occurred predominately in the small bowel in an average time of 2.4 h post dose. For HPMC capsules coated with Eudragit FS 30 D, complete disintegration did not occur until the distal small intestine and proximal colon in an average time of 6.9 h post dose.     

4-氨基水杨酸钠结肠定位片的研究

目的制备一种新型口服结肠定位制剂，并考察其体外释药行为与犬体内的结肠定位特性。方法本试验选择4-氨基水杨酸钠作为模型药物，应用丙烯酸树脂Eudragit RL30D，RS30D和Eudragit FS30D分别作为缓释和肠溶层包衣材料，制得包衣片剂，使系统可依赖pH和时间双重机制释药。在体外释放试验中，系统在0.1 mol·L^-1盐酸溶液中运转2 h后，分别在pH为6.5，7.0或7.4的磷酸盐缓冲液中继续运转12 h。体内验证以放射性同位素锝（^99mTc）做标记，用γ-射线显影法来确定系统在胃肠道内的释药时间和位置。结果体外实验中，系统在0.1 mol·L^-1盐酸溶液中运转2 h后无药物释放，在pH高于6.5的介质中缓慢释药，介质的pH越高，药物释放越快。体内实验中， 包衣片在胃肠道上半部无药物释放， 到达结肠后开始释药； 而非包衣片在犬胃部即迅速崩解。结论本文采用的包衣材料使包衣片到达升结肠时开始释放药物，药物释放时间可达10 h以上。     

Porous biodegradable microparticles for delivery of pentamidine.

The primary objective of this study was to develop a method for the preparation of porous biodegradable controlled release formulation of poly(lactide/glycolide) (PLGA). The model drug used for this study was pentamidine. Scanning electron microscopy pictures showed that these microparticles are highly porous and spherical in shape. A comparison of particle size reveals a similar median particle size (54-68 microm) in all six batches. The particles are all smaller than 90 microm. Differential scanning calorimetry thermograms revealed that pentamidine was mostly present in the crystalline form in the microparticles and did not dissolve in PLGA. The efficiency of encapsulation of pentamidine was higher than 58% in all six batches. The amount of drug released from these microparticles was at least 12% within the first 60 min. At least 50% of the total drug was released within the first 4 h. Drug release from these microparticles continued for up to 12 h. This faster drug dissolution was due to the highly porous surface. This highly porous surface will allow large molecules to release at a much faster rate than the regular microcapsules/microspheres.     

Stability and release characteristics of poly(D,L-lactide-co-glycolide) encapsulated CaPi-DNA coprecipitation

The aims of this work were to determine the stability of DNA-calcium-phosphate coprecipitation (CaPi-DNA) against various conditions during double emulsification microencapsulation and assess the release and physicochemical characteristics of poly(D,L-lactide-co-glycolide) (PLGA) microparticles loading CaPi-DNA. CaPi-DNA prepared at pH 6.5 showed a good stability with over 60% CaPi-DNA remained after emulsification, but no more than 40% at pH 8.0. Polyvinyl alcohol (PVA, 1-5%) could make over 80% CaPi-DNA (pH 7.0) preserved after homogenization. The dichloromethane (DCM), mixture of DCM and ethyl acetate, ether and n-hexane (1:1) exhibited neglectable influence on CaPi-DNA under homogenization. PLGA had influenced on CaPi-DNA without any additional stabilizer, in particular, PLGA (75:25, 4%, w/v) demonstrated a profound damage with only about 10% of the original CaPi-DNA remained. PLGA microparticles loading CaPi-DNA were spherical in shape with size range of 2.0-5.0microm, and entrapment efficiency 30-50%. CaPi-DNA was found to increase the stability of pDNA in PLGA microparticles without losing its structure integrity. The release of CaPi-DNA from microparticles showed a low burst release (<7.5%) within 24h and following sustained release process. The amount of cumulated CaPi-DNA release over 30 days was: 17.6% for PLGA (lactide:glycolide=50:50), 27.3% for PLGA (65:35) and 44.8% for PLGA (75:25) microparticles, respectively. The encapsulation of CaPi-DNA in microparticles could significantly protect CaPi-DNA from degradation of nuclease with average over 80% of total DNA recovery. These results suggested that the encapsulation of CaPi-DNA in PLGA microparticles could improve stability of pDNA.     

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.     

Controlled release from coated polymer microparticles embedded in tissue-engineered scaffolds

The controlled release of proteins in tissue-engineered implants is being examined with the potential application to improve vascularization and hasten tissue growth. Bovine serum albumin (BSA), was encapsulated within poly(D,L-lactic-co-glycolic acid) [PLGA] microparticles. The microparticles were coated with poly(vinyl alcohol) and incorporated into PLGA tissue-engineered scaffolds during fabrication. The release of BSA from PLGA microparticles, coated PLGA microparticles, and microparticles embedded in a porous PLGA scaffold was measured. We have developed a novel approach that will permit incorporation of coated polymeric microparticles during PLGA scaffold fabrication. Growth factors or drugs could be incorporated into the microparticles resulting in a long-term, controlled release.     

Comparison of chitosan and gelatin coated microparticles: prepared by hot-melt method

The aim of this study was to compare the performance of microparticles and their release properties after coating by chitosan and gelatin, respectively. All of the poly(epsilon-caprolactone) (PCL) microparticles were prepared by the hot-melt encapsulation method and indomethacin was selected as a model drug to be encapsulated. All of the coated microparticles retained their spherical shape irrespective of the type of coating material, and the particle size of coated microparticles was similar to the uncoated ones. The indomethacin encapsulation efficiency was in the range of 8.65 +/- 0.08 % - 8.81 +/- 0.04% for uncoated microparticles and 8.22 +/- 0.04% - 8.68 +/- 0.08% for coated microparticles. The release of indomethacin from uncoated microparticles followed a two-exponential release profile, where indomethacin was rapidly released within 4 h during the first release phase, after that approximately 20% of the drug was continuously and slowly released for up to 24 h in the second phase. The similar release profile was observed from coated microparticles irrespective of the times of coating and the types of coating material. Both the natural coating materials, chitosan and gelatin, efficiently reduced the initial burst release and the first phase of drug release, but did not alter the second phase of drug release. In other words, chitosan and gelatin could be used to protect the drug on the surface of microparticles from immediately contacting with the release medium and both possessed the same feature in the delay of drug release.     

Design,optimization and evaluation of mesalamine matrix tablet for colon drug delivery system

The aim of the present investigation was to develop and evaluate matrix tablet of mesalamine for colonic delivery by using Eudragit RSPO, RLPO and combination of both. The tablets were further coated with different concentration of pH-dependent methacrylic acid copolymers (Eudragit S100), by dip immerse method. The physicochemical parameters of all the formulations were found to be in compliance with the pharmacopoeial standards. The in vitro drug release study was conducted using sequential dissolution technique at pH 1.2 (0.1N) HCl, phosphate buffers pH 6.8 and 7.4, with or without rat cecal content mimicking different regions of gastro intestinal tract. The result demonstrated that the tablet containing Eudragit RLPO coated with Eudragit S100 (1 %) showed a release of 94.91 % for 24 h whereas in the presence of rat cecal content the drug release increases to about 98.55 % for 24 h. The uncoated tablets released the drug within 6 h. The in vitro release of selected formulation was compared with marketed formulation (Octasa MR). In vitro dissolution kinetics followed the Higuchi model via non-Fickian diffusion controlled release mechanism. The stability studies of tablets showed less degradation during accelerated and room temperature storage conditions. The enteric coated Eudragit S100 coated matrix of mesalamine showing promising site specific drug delivery in the colon region.     

Development of novel budesonide pellets based on CODES(TM) technology: In vitro/in vivo evaluation in induced colitis in rats

Background and the purpose of the study

Budesonide is the drug of choice for treatment of active inflammatory bowel disease (IBD). The aim of this study was to develop budesonide pellets based on a novel colon drug delivery system (CODES).

Methods

Pellet cores containing lactulose or mannitol were prepared by extrusion/spheronization and coated with an acid soluble polymer (Eudragit E100), hydroxypropylmethyl cellulose (HPMC) and an enteric coat (Eudragit FS 30D) sequentially. In vitro drug release of coated pellets was studied using USP dissolution apparatus type II in buffers of pH 1.2 (2 hrs), pH of 7.4 (4 hrs) and pH of 6.8 containing 8% rat cecal contents (RCC) (18 hrs). The efficacy of the optimized formulation (containing 50% lactulose coated with Eudragit E (30% w/w) and Eudragit FS 30D (12% w/w)) was evaluated against 2, 4, 6-trinitrobenzenesulfonic acid (TNBS)-induced colitis in rats.

Results

The results of the kind of bacteria in vitro dissolution tests indicated absence of drug release in pHs of 1.2 and 7.4 and controlled release in buffer of pH 6.8 containing RCC. It was found that release rate was controlled by the type and amount of polysaccharide and the thickness of the acid soluble layer. The prepared formulation showed promising results in alleviating the conditions of experimental model of colitis.

Conclusion

The results of this study suggest that pellets based on CODES technology could be useful for colonic delivery of budesonide.     

Controlled Release from Coated Polymer Microparticles Embedded in Tissue-engineered Scaffolds

The controlled release of proteins in tissue-engineered implants is being examined with the potential application to improve vascularization and hasten tissue growth. Bovine serum albumin (BSA), was encapsulated within poly(D,L-lactic-co-glycolic acid) [PLGA] microparticles. The microparticles were coated with poly(vinyl alcohol) and incorporated into PLGA tissue-engineered scaffolds during fabrication. The release of BSA from PLGA microparticles, coated PLGA microparticles, and microparticles embedded in a porous PLGA scaffold was measured. We have developed a novel approach that will permit incorporation of coated polymeric microparticles during PLGA scaffold fabrication. Growth factors or drugs could be incorporated into the microparticles resulting in a long-term, controlled release.     

Effects of alginate coated on PLGA microspheres for delivery tetracycline hydrochloride to periodontal pockets

The effects of alginate coated on tetracycline (Tc) loaded poly (D, L-lactic-co-glycolic acid) (PLGA) microspheres fabricated by double emulsion solvent evaporation technique for local delivery to periodontal pocket were investigated. Alginate coated PLGA microspheres showed smoother surface but enlarged their particle sizes compared with those of uncoated ones. In addition, alginate coated microspheres enhanced Tc encapsulation efficiency (E.E.) from 11.5?±?0.5% of uncoated ones to 17.9?±?0.5%. Moreover, all of the coated PLGA microspheres even fabricated at different conditions could prolong Tc release from 9–12 days with 50% or higher in cumulative release of Tc compared with those of uncoated ones. The swelling ratios of PLGA microspheres for alginate coated or uncoated ones, one of the possible mechanisms for enhancing Tc release for the coated ones, were measured. The results showed that 20% or higher in swelling ratio for the coated microspheres at the earlier stage of hydration (e.g.?≤?24?h) could be an important factor to result in high Tc release compared to the uncoated ones. In conclusion, alginate coated Tc loaded PLGA microspheres could enhance Tc delivery to periodontal pocket by enhancing drug encapsulated efficiency, released quantities and sustained release period compared with uncoated ones.     

Influence of hydroxyethylcellulose on the drug release properties of theophylline pellets coated with Eudragit RS 30 D.

The objective of this study was to investigate the influence of a hydrophilic polymer, hydroxyethylcellulose (HEC), on the release properties of theophylline from pellets coated with Eudragit RS 30 D, and the physicochemical properties of Eudragit RS 30 D cast films. The release rate of theophylline from Eudragit RS 30 D coated pellets decreased during storage at 25 degrees C/60% RH due to the further coalescence of colloidal acrylic particles. In addition, water-vapor permeability and tensile strength of Eudragit RS 30 D cast film decreased after 1-month storage at 25 degrees C/60% RH. The presence of 10% hydroxyethylcellulose in the coating formulation was shown to stabilize the drug release rate from coated pellets, the water-vapor permeability and the tensile strength of free films. Atomic force microscopy and scanning electronic microscopy were used to demonstrate that the HEC was immiscible with Eudragit RS 30 D in the cast films. The stabilization effect of HEC was investigated and determined to be due to the formation of an incompatible phase between the latex particles which impaired further coalescence of the colloidal acrylic particles.     

Evaluation of Mucoadhesive PLGA Microparticles for Nasal Immunization

In this study, hepatitis B surface antigen (HBsAg) loaded poly(lactic-co-glycolic acid) (PLGA) microparticles were prepared and coated with chitosan and trimethyl chitosan (TMC) to evaluate the effect of coating material for nasal vaccine delivery. The developed formulations were characterized for size, zeta potential, entrapment efficiency, and mucin adsorption ability. Plain PLGA microparticles demonstrated negative zeta potential. However, coated microparticles showed higher positive zeta potential. Results indicated that TMC microparticles demonstrated substantially higher mucin adsorption when compared to chitosan-coated microparticles and plain PLGA microparticles. The coated and uncoated microparticles showed deposition in nasal-associated lymphoid tissue under fluorescence microscopy. The coated and uncoated microparticles were then administered intranasally to mice. Immune-adjuvant effect was determined on the basis of specific antibody titer observed in serum and secretions using enzyme-linked immunosorbent assay. It was observed that coated particles showed a markedly increased anti-HBsAg titer as compared to plain PLGA microparticles, but the results were more pronounced with the TMC-coated PLGA microparticles.     

In vitro evaluation and pharmacokinetics in dogs of guar gum and Eudragit FS30D-coated colon-targeted pellets of indomethacin

A pH- and enzyme-dependent colon-targeted multi-unit delivery system of indomethacin was developed by coating guar gum and Eudragit FS30D sequentially onto drug-loaded pellets in a fluidized bed coater. In vitro studies showed that smaller coating weight gain of guar gum resulted in reduced release lag time t10 (10% release time), but favored degradation by enzymes (galactomannanase). A cumulative weight gain (CWG) of 44% provided sufficient enzymatic sensitivity and protection of the core. Under gradient pH conditions (pH = 1.2, 6.8, 7.4 and 6.5 for 2, 2, 1 and 15 h, respectively), indomethacin was released from Eudragit FS30D-coated pellets quickly after changing pH to 7.4. For guar gum/Eudragit FS30D double-coated pellets, only about 5% of the drug was released after another 1 h, showing retarding effect by guar gum coating. After changing pH to 6.5 and addition of galactomannanase, enzyme-dependent drug release was observed. Pharmacokinetic study in beagle dogs showed that fastest absorption with the smallest Tmax and Tlag was observed for uncoated pellets. The Tmax and Tlag of Eudragit FS30D-coated pellets were postponed to about 2.5 and 1 h, respectively. After a further guar gum coating, Tlag was further postponed to about 2.8 h, about 2 h of additional lag time on the basis of Eudragit FS30D coating. It is indicated that the guar gum/Eudragit FS30D-coated system has potential to be used to deliver drugs to the colon.     

Dissolution stability studies of suspensions of prolonged-release diclofenac microcapsules prepared by the Wurster process: I. Eudragit-based formulation and possible drug-excipient interaction

The aim was to evaluate possible interaction in solid and liquid state of the drug with formulation excipients consequent to very fast drug release of diclofenac-Eudragit prolonged release microcapsules. The microcapsules were prepared by drug layering on calcium carbonate cores and coated with Eudragit RS 30D and L30D-55 as previously reported. Suspension of the microcapsules was prepared using microcrystalline cellulose/sodium carboxymethyl cellulose (Avicel CL-611) as medium. In vitro dissolution testing of the suspension was done, and, based on the dissolution results, possible interaction between diclofenac and Eudragit and Avicel in the medium was studied. Powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC) analyses were performed using 1:1 binary, 1:1:1 ternary mixtures and a ratio equivalent to that in the formulation. The mixtures were prepared by mixing the dispersions--Eudragit RS 30D or L30D-55 with the drug or other components, followed by drying at 60 degrees C for 48 h. Dry mixing was done using the powder equivalents of the polymers, Eudragit RS PO and L100-55, Avicel and calcium carbonate. In vitro dissolution of the suspended microcapsules showed a very fast release after 48 h (T50 = <1 h) compared to the solid microcapsules (T50 = 6 h). DSC curves of the formulation components or microcapsules did not show the characteristic endothermic peak of diclofenac at 287 degrees C. Powder X-ray diffraction of the binary or ternary mixtures of diclofenac and Eudragit polymers indicated reduction, shift or modification of the crystalline peaks of the drug or excipients at 2theta of 12 degrees and 18 degrees , suggestive of interaction. Some changes in drug peak characteristics at 18 degrees and 23 degrees were observed for Avicel/drug mixture, though not significant. The DSC curves of the binary mixture of diclofenac co-dried with liquid forms of Eudragit (i.e. RS 30D or L30D-55) revealed greater interaction compared to the curves of drug and powdered forms of Eudragit (RS PO or L100-55). This was depicted by greater shift in fusion points of the mixtures relative to the drug. However, comparing the RS and L-type Eudragit, the latter generally showed greater interaction with the drug. Interaction between diclofenac and L-type Eudragit polymers can occur in liquid formulations.