Dissolution rate of griseofulvin in bile salt solutions.
Bile salts increase the apparent solubility of lipophilic poorly water-soluble drugs like griseofulvin. In this study, the dissolution kinetics of griseofulvin in solutions of bile salts (sodium taurocholate and sodium cholate) were investigated. A rotating disk apparatus was chosen to monitor dissolution kinetics; it well-defined hydrodynamic conditions allowed for analysis of the behavior of bile salt micelles under different conditions. Griseofulvin solubility and dissolution rate increased with increasing bile salt concentration in the dissolution medium. The enhancement of the dissolution rate was not linearly related to the solubility increase, as diffusional transport of the solubilized drug proved to be less efficient than transport of the unsolubilized ("free") drug. The dissolution process proved to be controlled by convective diffusion. An analysis of the data with the phase separation model provided results for the micellar diffusion coefficient comparable with literature data obtained with different techniques.
de Smidt
J H
JH
Department of Pharmaceutics, Faculty of Pharmacy, Utrecht University, The Netherlands.
Offringa
J C
JC
Crommelin
D J
DJ
D001647:Bile Acids and Salts / Q000737:chemistry*; D019826:Cholic Acid; D002793:Cholic Acids / Q000737:chemistry; D004058:Diffusion; D006118:Griseofulvin / Q000737:chemistry* / Q000493:pharmacokinetics; D007700:Kinetics; D008823:Micelles; D008956:Models, Chemical; D012995:Solubility; D013656:Taurocholic Acid / Q000737:chemistry
D001647:Bile Acids and Salts; D002793:Cholic Acids; D008823:Micelles; D006118:Griseofulvin; D013656:Taurocholic Acid; D019826:Cholic Acid