Improving the high variable bioavailability of griseofulvin by SEDDS

Abstract

To enhance the dissolution and oral absorption of poorly water-soluble griseofulvin (GF), self-emulsifying drug delivery system (SEDDS) composed of oil, surfactant and cosurfactant for oral administration of griseofulvin was formulated, and its physicochemical properties and pharmacokinetic parameters were evaluated. The solubility of griseofulvin was further improved by the addition of hydrochloric acid. Droplet size of griseofulvin emulsion was kept constant both in simulated gastric fluid without pepsin and simulated intestinal fluid throughout 12 weeks incubation period. Griseofulvin in the SEDDS rapidly dissolved in different dissolution media. This was not the case for the commercial GRIS-PEG® tablets. In different fed diet groups, AUC 0→24 h, Cpmax, and Tmax of griseofulvin after oral administration of SEDDS in rats were comparable to those after oral dose of GRIS-PEG® tablet. Although, in fed lipidic diet group, the mean AUC and Cpmax after oral administration of GRIS-PEG® in rats were 1.28 and 1.15 fold higher, respectively, compared with those of SEDDS, these have not shown to be significantly different. These results demonstrate that the SEDDS of griseofulvin composed of Capmul® GMO-50, Poloxamer and Myvacet 9-45 greatly enhanced the dissolution of griseofulvin (without ultramicronisation). However, food intake effect on the bioavailability of griseofulvin has remained. Thus, this system may provide a useful dosage form for oral water-insoluble drugs which have problems in their dissolution. © 2007 Pharmaceutical Society of Japan.