Colon Delivery of Naproxen: Preparation, Characterization and Clinical Evaluation in Healthy Volunteers

Abstract

Naproxen is a steroidal anti-inflammatory drug and is used in the treatment of rheumatoid arthritis, osteoarthritis and colitis. When administered orally in conventional form results in undesirable gastrointestinal toxicity and poor delivery of the drug to the colonic region. In this study, colon targeted delivery system of naproxen was developed to reduce side effects and achieve high local drug concentration at the afflicted site in the colon. Core tablets of naproxen were formulated with HPMC K4M polymer by wet granulation method. The prepared tablets were evaluated for physical parameters and in vitro drug release. The tablets were coated with Eudragit S100 and Eudragit L100 with triethyl citrate as a plasticizer. The coated tablets were evaluated for physical parameters and in vitro drug release. Drug excipient compatibility studies by using FTIR were analysed. Further, in vivo colon residence time of naproxen in healthy human volunteers was performed by radio imaging study. From the results, formulation EL4 also performed better in vitro release but ES2 was considered more superior because of the former’s dependence on GI transit time for drug release and total weight gain of 7.5% at a concentration of 20% dry weight of the polymer with plasticizer and was not specific to pH of the colon and a weight gain of 20% is needed in case of tablets coated with Eudragit L100. Hence ES 2 was considered as the optimized formulation for colonic drug delivery. These results were confirmed with the results of X-ray studies in three healthy human volunteers