Development of ileo colonic targeting drug delivery for treatment of inflammatory bowl disease

Abstract

Micro-biotically activated ileo-colonic delivery of budesonide (BUD) and azathioprine (AZA) newlinefrom compression coated tablets with considerably reduced carboxymethyl chitosan (CMCH) newlineconcentration was designed and investigated. CMCH was synthesized from chitosan dissolved in newline20% w/v sodium hydroxide (NaOH) with monochloroacetic acid at 40±5°C and characterized by newlineproton NMR, FTIR and Degree of Substitution (Ds). The micro-biotically activated compression newlinecoated tablets (MACC-TABs) were prepared by wet granulation and compression coated with newlineEudragit S100: HPMC K100M in different ratios for enteric protection and ileo-colon selectivity. Dissolution studies without enzymes and in presence of enzymes such as pepsin at pH 1.2, diastase newlineand pancreatin at pH 6.8, the F1C3 did not show significant changes. Addition of colonic enzymes newlineat the tenth hour, resulted in significant increase in release of budesonide. The % Cumulative Drug newlineRelease (%CDR) was BUD (98.49±1.42%) and AZA (98.87±1.06%)., due to the enzymatic newlinetriggering (produced by the colonic microflora) leading to the lysis of glycosidic bonds. Scanning newlineElectron Microscopy (SEM) revealed the pores formed after dissolution was due to the watersoluble newlinenature of CMCH to release the drug. The evidence during in-vitro dissolution studies newlineconfirmed the pH sensitivity along with microbiotic activation of the MACC-TABs tablets to efficiently and reproducibly release budesonide in the ileo-colon site in presence of the bacterial newlineenzymes. newline