Formulation and Evaluation of Microbial Triggered Colon Specific Delivery of Azathioprine
Abstract
Purpose: The Thioguanine derivative, Azathioprine (AZA) is a prodrug of 6-mercaptopurine that is further metabolized by various enzymes present in the liver and gut have proven efficacy in the treatment of inflammatory bowel disease (ulcerative colitis) in 2-2.5 mg/kg/day at 0,2 and 6 weeks than every 8 week and also may reduce the need for steroid treatment. In the present work sustained release formulation of azathioprine was developed with an objective to achieve colon specific drug delivery with reduced frequency of dosing, to minimize gastric side effect and thus to increase patient compliance.
Method: The six different tablet formulations were prepared by direct compression method using Guar gum (GG), and xanthan gum (XG). Tablets are evaluated for their physicochemical properties and in vitro drug release studies. Biodegradability studies of guar and xanthan gum was carried out in presence of 4% w/v RCC and galactomannase enzyme (0.1 mg/ml.) by viscosity measurement using Brookfield viscometer and significant decrease in viscosity was found with 4% RCC after 24 h incubation.
Result: In the rat caecal contents formulations shows enhanced drug release due to degradation of guar gum coat by colonic galactomannanase enzyme. The tablets containing guar (G1) released 70.07 %, at the end of 24th hour in rat caecal contents whereas, drug release from tablets containing a xanthan gum (X6) 79.06 % at the end of 24th hour.
Conclusion: From the results of this study it appears that, the proposed microbial triggered matrix tablet of Optimized X6 formulation azathioprine (500 mg) conventional tablet with better control of drug release for targeted drug delivery. In addition developed colon-specific drug delivery system (CDDS) was relatively inexpensive and easy to manufacture using other techniques.
