New Dissolution Method for Mesalamine Tablets and Capsules

Dissolution methods are different for extended-release mesalamine capsules (pH 7.5 only) and delayed-release tablets (pH 1.4, 6.0, and 7.2). Mesalamine is used for the treatment of ulcerative colitis. The USP methods have several drawbacks in that they do not mimic gastrointestinal tract environments; tablets are removed from vessels to change dissolution medium; and neither method has been adopted to compare different formulations. This study proposed a method that reflects gastrointestinal transit time and pH, is easy to conduct, and may be used to test new delayedor extended-release formulations and compare various dosage forms. e-mail: [email protected] at testing one commercially available extended-release mesalamine capsule (Pentasa, 250 and 500 mg) and one delayed-release tablet (Asacol, 400 mg) using the USP dissolution methods to identify the shortcomings of each methodology. Pentasa beads have a coating of ethylcellulose, while Asacol tablets are coated with Eudragit S. Also suggested is a new dissolution method that reflects gastrointestinal transit times (5) and could be used to compare various mesalamine solid dosage forms simultaneously. MATERIALS AND METHODS Reagents and Standards Mesalamine was gift of TEVA Pharmaceuticals. Hydrochloric acid, sodium hydroxide, and potassium phosphate were ordered from Fisher Scientific (Fair Lawn, NJ). Commercial Capsules and Tablets Pentasa (mesalamine controlled-release capsules, 250 and 500 mg) and Asacol (mesalamine delayed-release tablets, 400 mg) were obtained from OSU Campus Pharmacy. USP Dissolution Method for Extended-Release Mesalamine Capsules Phosphate buffer (0.05 M) at pH 7.5 was prepared by dissolving 6.8 g of monobasic potassium phosphate and 1 g of sodium hydroxide in water to make 1000 mL of solution and adjusting the pH to 7.5 ± 0.05 with 1.0 N sodium hydroxide. Pentasa in vitro dissolution study was accomplished using a USP Apparatus II. Each vessel was filled with 900 mL of preheated (37 °C) deaerated 0.05 M phosphate buffer at pH 7.5 as receptor medium. The paddle rotation speed was set at 100 rpm. The water bath was maintained Corresponding author. INTRODUCTION Inflammatory bowel disease (IBD) refers to a group of diseases that principally affect the small and large intestines and is characterized by chronic inflammation of unknown etiology. The two major clinical entities are ulcerative colitis and Crohn’s disease. They have several overlapping features. Crohn’s disease can affect both the small and large bowels in a given patient as well as any other segment of the gastrointestinal tract (GIT). In contrast to ulcerative colitis, Crohn’s disease is much less responsive to sulfasalazine. The drug is now seldom used for this condition, having been replaced by the newer 5-ASA preparation, mesalamine (1). The mesalamine dosage forms available in the FDA Orange Book are rectal enema, rectal suppository, extended-release oral capsule, and delayed-release oral tablet. In spite of the reported success of several in vitro–in vivo correlation studies, dissolution is not a predictor of therapeutic efficiency (2, 3) because of the complexity of the absorption process and drug distribution to the site of action. However, it can best be described as a qualitative tool that can provide valuable information about the biological availability of a drug product. The USP dissolution methods (4) are different for extended-release mesalamine capsules (performed at pH 7.5 only) and delayed-release tablets (performed at pH 1.4 for 2 h, pH 6.0 for 1 h, and finally at pH 7.2). GIT transit times (Table 1) are not reflected in the USP methods for extended-release mesalamine capsules. Additional drawbacks include (1) food effects on drug release are not considered, (2) tablets are removed from vessels to change dissolution medium, and (3) neither method has been adopted to compare different formulations together. Thus, this study was aimed diss-15-03-08.indd 7 8/6/2008 1:40:55 PM dx.doi.org/10.14227/DT150308P7