Development of Novel Drug Delivery Systems for the management of NSAID induced Gastroenteropathy A Quality by Design QbD approach

Abstract

Abstract newlineManagement of Nonsteroidal anti-inflammatory drugs (NSAID)-induced newlinegastroenteropathy has emerged as an important medico-socioeconomic problem. There are newlineno approved therapeutic agents to prevent NSAID-induced enteropathic damage and its newlineexacerbation by proton pump inhibitors (PPIs; viz. pantoprazole sodium, PTZ). Hence, the newlineprimary objective of the present study was to develop the novel formulations of quercetin newline(QCT) and PTZ to prevent NSAID-induced gastroenteropathic damage and exacerbation of newlineenteropathic damage caused by PTZ. newlineHowever, since these novel formulations were required to be tested in an animal newlinemodel, hence; a clinically simulated rat model for NSAID-induced gastroenteropathy was newlinedeveloped. Using this model, the anti-gastroenteropathic potential of QCT was proven newlineagainst NSAID-induced gastroenteropathy and exacerbation of enteropathic damage caused newlineby PTZ. Further, sodium alginate based systematically optimized multiple-unit newlinegastroretentive drug delivery system (GRDDS) of QCT and enteric coated formulation of newlinePTZ were developed using quality by design (QbD) approach. A 3 3 Box Behnken design newline(BBD) was employed for optimizing the formulations. newlineOptimized formulation of QCT prevented the NSAID-induced gastroenteropathic newlinelesions at reduced dose levels (25 mg kg -1 ) compared to non-formulated QCT (50 mg kg -1 ) newlineand enteric coated formulation of PTZ did not exacerbate the NSAID-induced enteropathic newlinedamage. While, co-administration of QbD-enabled novel formulations of QCT (25 mg kg -1 ) newlineand PTZ (4 mg kg-1 ) prevented the NSAID-induced gastroenteropathic damage successfully. newlineOral toxicity study (28 days) of the optimized formulations of QCT and PTZ newlineestablished the safety of these NDDS in healthy male wistar rats. Further, it can be inferred newlinefrom toxicity study that PTZ/PTZ loaded microparticles and QCT/QCT loaded newlinemicroparticles up to and inclusive of 16 mg Kg-1 and 100 mg Kg-1 body weight twice daily newlinerespectively was tolerated by the rats up to 28 days. newlineBased on these findings, it can be concluded