Synthesis, Characterization and Biological Screening of Mutual Prodrug of Etodolac-Dextran: An Approach to Reduce Toxicity | Original Article

ABSTRACT:

Objective The project was aimed at synthesizing and characterizing conjugate of Etodolac (ETD) that is expected to enhance solubility without affecting permeability and is capable of delivering ETD to colon without significant reversion of prodrug in gastrointestinal conditions. Methods Thus, Etodolac- dextran (ETD-DEX) conjugate was pre-pared by conventional coupling method and the prodrug was characterized by FTIR, FAB mass and elemental analysis. The conjugate was then subjected to selected pharmaceutical preformulation studies like aqueous solubility analysis and pH partition studies. Results These studies established 1.24 folds higher solubility of the ETD-DEX over ETD in phosphate buffer pH 6.8 without compromising its partitioning ability. The in vitro stability studies suggested its potential of safe transit to colon where the moiety is capable of reverting to 90.52 ETD after 48 hrs of the experiment. In vivo evaluation of ETD-DEX in an experimentally induced colitis established its efficacy an anti-inflammatory prodrug moiety that was supported by histological studies. In addition to its ability to control colonic ulcers ETD-DEX demonstrated insignificant (P >0.05) gastric ulcerogenic potential. Colonic MPO activity for ETD-DEX in mU100 mg tissue was found to be 54.97 which were much less than plain ETD (85.54). Conclusion Conclusively, the conjugate when suitably formulated can be considered as therapeutically efficacious drug delivery system with fewer pharmaceutical limitations.