FORMULATION AND IN-VIVO EVALUATION OF MESALAMINE MICROSPONGES FOR COLON TARGETING

The present study aims to develop and characterize colon-targeted mesalamine microsponges for treating inflammatory bowel disease, requiring long-term therapy. Mesalamine microsponges were prepared with different ratios of eudragit S100, by quasi-emulsion solvent diffusion method and evaluated. The drug release from in-vitro dissolution for all the prepared microsponges was extended to 12 hrs and above, and release kinetics followed a biphasic pattern with Higuchi non-fiction diffusion predominantly. SEM images clearly showed drug entrapment effectively in the microsponges based on the % yield, entrapment efficiency, drug content, and complete drug release (12-15 hrs). Microsponges prepared with a drug-to-polymer ratio of 5:1 (ES5) were considered suitable formulations. Microsponges were equivalent to a dose of 500 mg and were compressed into core tablets by direct compression. All the tableting parameters complied with the official compendia test for tablets as per IP. As the compression of the microsponges did not alter the release, tablets were further subjected to compression coating with cellulose acetate phthalate for colon targeting. From in vitro dissolution studies, drug release from the compression-coated microsponge tablets was extended for a period ranging between 30-36 hrs, and in a probiotic medium, complete drug release was obtained between 30-34 hrs due to the presence of microflora. Drug-excipient compatibility studies using FTIR, XRD, and DSC indicated no interactions. Compression-coated tablets of microsponges prepared with eudragit S100 (CT-ES5) showed faster release of drug i.e. in 30 hours inclusive of desired 6 hrs lag time, and were selected for carrying out in vivo evaluation. Notable changes were not observed after long-term and accelerated stability studies according to ICH guidelines for India. ES5 microsponges were equivalent to 5 mg of mesalamine were compressed into mini core tablets of 2 mm diameter and were further compression coated with 10 mg of CAP to obtain compression coated tablet (RCT-ES5) having a diameter of 4 mm for administration to rat. As dissolution profiles of RCT-ES5 and CT-ES5 were superimposable RCT-ES5 was tested in rats for pharmacodynamic activity. Colonic tissue sections from RCT-ES5 treated rats markedly reduced the induced disease, as observed from macroscopic and histopathological studies. Predominant local action can be confirmed for RCT-ES5 when compared to pure mesalamine. The superiority of compression-coated mesalamine microsponge tablets for colon targeting is thus obtained.