English

Abstract

About 50% of an oral dose of griseofulvin passes through the gastro-intestinal tract unabsorbed and is excreted in faeces. Short residence time of the low soluble griseofulvin, in stomach and small intestine, limits its dissolution.  Griseofulvin is highly soluble in acidic pH, and so a gastro-retentive floating matrix system was developed to control dissolution rate and thereby enhance solubility to develop an improved and convenient dosage form. Preformulation studies included selection of excipients and evaluation of compatibility with griseofulvin. Tablets were prepared by wet granulation technique with varying ratios of Methocel™, Accurel MP and Polyvinylpyrrolidone as determined by Design Expert software. Buoyancy capability and dissolution studies were carried out to assess the influence of the tablet components. Tablets that float immediately upon contact with dissolution medium and continue floating for over 12 h were achieved with at least 28% of Accurel MP. An increase in tablet hardness reduced the rate of griseofulvin release only up to 120 min. Methocel™ had the most significant influence on griseofulvin release, with an indirect proportion to the rate of griseofulvin release. Using Design Expert software, optimized formulation was achieved with 1% Polyvinylpyrrolidone, 30% Methocel™, 60% Accurel MP and hardness ranging between 8 and 9 N. Tablets produced floated immediately upon contact with the medium and remained floating for at least 12 h. Griseofulvin was released from the optimized tablets in a near zero order fashion, with a total of 80.8% griseofulvin released at the end of the 12-h dissolution test period. Key words: Griseofulvin, gastro-retentive, floating tablets.