Evaluation of the effect of co‒grinding on dissolution rate of poor water soluble drug (clarithromycin)

Abstract

Most of the newly invented active pharmaceutical ingredients APIs are poor water soluble and dissolution rate is the limiting step in bioavailability from compressed solid dosage forms Objective of the study was to elucidate the effect of hydrophilic carriers on dissolution rate of poor water soluble drug and utilization of co grinded Clarithromycin in preparation of tablets by direct compression Intrinsic dissolution rate of Clarithromycin was determined according to United States Pharmacopeia USP using rotating disk method Hydrophilic carrier micro crystalline cellulose was applied in varying ratios and drug to carrier ratio by weight for enhancement of dissolution rate of Clarithromycin by co grinding technique Co grinded Clarithromycin was prepared by compressing lubricated physical mixture blend of Clarithromycin and micro crystalline cellulose to slugs followed by granulation Tablets containing co grinded Clarithromycin were prepared by direct compression technique and evaluated for various official and unofficial parameters at pre compression and post compression level The prepared tablets were compared with marketed tablets in terms of physical parameters mechanical strength disintegration behavior and in vitro drug release Dissolution profiles of both types of the tablets were compared on the basis of maximum drug release dissimilarity factor f similarity factor f and dissolution efficiency Clarithromycin is a class II drug with poor water solubility Its intrinsic dissolution rate is very low mg cm min In comparison to intrinsic dissolution rate significant increase in dissolution rate of Clarithromycin was observed by co grinding with hydrophilic carriers Dissolution rate of Clarithromycin enhanced with concentration of hydrophilic carrier and maximum increase was observed at drug to carrier ratio by weight By further increasing ratio of the carrier resulted in decrease in dissolution rate due to cushioning effect Tablets containing co grinded Clarithromycin showed better dissolution profile compared with marketed tablets In comparison with marketed tablets maximum drug release in min Q plusmn Q plusmn Q plusmn and dissolution efficiency were higher for tablets containing co grinded Clarithromycin Dissolution rate of poor water soluble drug Clarithromycin can be enhanced by co grinding with hydrophilic carrier micro crystalline cellulose Co grinding is an environment friendly technique that can be applied for enhancement of dissolution rate of poor water soluble APIs irrespective of nature and dose