Abstract

Background: Colorectal carcinoma is the fourth most common internal malignancy; it is second only to carcinoma of the lung as a cause of carcinoma death. 6-Mercaptopurine (6-MP) is a drug of choice in the treatment of Crohn's disease, ulcerative colitis and colorectal cancer. The drug shows irritation on gastric exposure. It has poor bioavailability with half life less than 2 h. Targeted delivery of 6-MP will provide an effective and safe therapy for colon diseases.

Objective: Objective of the present work was to design, develop and optimize colon targeted delivery with help of polymers guar gum and HPMC K100 for 6-Mercaptopurine, which will act as site targeted delivery for treatment of colon diseases.

Method: Targeted delivery was prepared by press/compression coating technique. Preliminary study had shown 4:1 ratio of microcrystalline cellulose and croscarmellose sodium was optimum for core tablet. 3² full factorial design was applied. Amount of guar gum and hydroxypropyl methylcellulose (HPMC K100) were employed as independent variables while responses evaluated were hardness and swelling index at 5 h.

Results: Optimized GD batch contain 26.32% and 73.68% w/w of total polymer weight of guar gum and HPMC K100, respectively. This prevented the release of drug in the gastric region and allowed drug release ≥90% in colonic region after ≥8 h. In-vivo x-ray imaging placebo study revealed that, tablet was observed in colonic part at 5h and disintegrated at ~ 8 h. Optimized formulation was found to be physically and chemically stable.

Conclusion: Optimize GD batch had shown retardation of the drug release in upper GI tract which will enhance therapeutic activity of the drug at the site. This system hence will act as a potential site and time controlled colon targeted delivery.

Keywords: 6-Mercaptopurine, guar gum, HPMC K100, press coated, colon, optimization.