Synthesis and Evaluation of some Nonsteroidal Antiinflammatory Polymeric Pro drugs for Sustained Drug Delivery

Abstract

This thesis deals with the investigations carried out by the writer on the synthesis and evaluation of some non steroidal anti-inflammatory polymeric pro-drugs for sustained drug delivery. The first chapter of the thesis deals with a brief introduction to controlled drug delivery systems, role of polymeric materials in drug delivery, release characteristics of polymeric pro-drugs, the use of NSAIDs and the problems associated with their use and the literature survey on the investigations that have been carried out on polymeric drug conjugates for the drugs selected in the present investigation, The second chapter of the thesis explains the scope and object of the present investigation in detail. It explains, in particular, how when an NSAIDs linked covalently to a biocompatible polymer through an ester linkage should lead to a drug delivery system capable of releasing the drug predominantly at the lower GI tract in a sustained and site-specific manner. The third chapter of the thesis deals with the experimental procedures that are followed in the preparation of the polymeric pro-drugs, estimation of drug content, in vitro drug release studies, release kinetics, antiinflammatory and ulcer inducing effects of the prodrugs. The fourth chapter of the thesis deals with the results obtained in the present study along with the discussion of the results supported by chemical equations, tables, figures, etc. The following are some of the important findings in the present study; Six polymeric pro-drugs of Diclofenac, Ibuprofen, Flurbiprofen using poly (ethylene glycol) with two different molecular weights, PEG 999 and PEG;590, have been synthesised and characterised. The pro-drugs synthesised have been studied for their in vitro drug release behaviour at pH 1.2, pH 4.5, pH 6.8 and 7.2. The in vitro drug release behaviour clearly show that the drug releases is slower at the gastric pH and place predominantly at the alkaline pH as hypothesised in the present study. Further, the drug release also takes place in a sustained manner.