International Journal of Pharmaceutics, 82 (1992) 47- 52 % 1992 Elsevier Science Publishers B.V. All rights zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA reserved 0378-5173/92/$05.00 IJP 02701 Development and in vitro evaluation of griseofulvin gels using Franz diffusion cells M.D. Vlachou, D.M. Rekkas, P.P. Dallas and N.H. Choulis DirGion of Pharmaceutical Technology, Department of Pharmacy, Uniwsity of Athens, P.O. Box 4315, Athens 102 IO (Greece) (Received 9 August 1991) (Modified version received 8 November 1991) (Accepted 1.5 November 1991) Key words: In vitro evaluation; Griseofulvin gel; Franz diffusion ceI1 The strong antidermatophytic action of griseofulvin, following oral administration, results from its concentration in the stratum corneum. However, this route of administration is often associated with various side effects. The purpose of this work was the preparation and in vitro evaluation of several gel formulations of griseofulvin, in which the drug was dissolved, for further clinical studies as an alternative topical dosage form. The in vitro release profiles of these formulations through artificial membranes and excised human skin, determined using Franz diffusion cells, showed that griseofulvin is released from the topical gel formulations employed and diffuses through skin. Additionally, stability studies conducted under room conditions for 16 months indicated that these formulations were adequately stable. Finally. preliminary clinical studies in humans showed that griseofulvin gels were effective and also well tolerated. Introduction Griseofulvin, which is known to be a very effective fungistatic antibiotic when administered orally, concentrates in the stratum corneum be- tween 4 and 8 h after administration (Shah et al., 1974). This oral route, however, is often associated with side effects such as headaches, gastrointesti- na1 disturbances, blood dyscrasias, hepatotoxicity Correspondence: N.H. Choulis, Department of Pharmacy, Di- vision of Pharmaceutical Technology, P.O. Box 4315, Athens 102 10, Greece. and gynecomastia (Martindale, 1982; Ritschel and Hussain, 1988). Several investigators have attempted to evalu- ate the effectiveness of the topical route of ad- ministration. Zarowny et al. (197.5) reviewed a number of positive and negative reports on the topical application of griseofulvin, and their re- sults suggested that the drug may be effective following topical administration. Skin concentrations resulting from a single topical application have been reported to be much higher than those obtained after prolonged oral administration (Epstein et al., 197.5). Despite this observation and the fact that several investigators have shown the effectiveness of topically applied