DEVELOPMENT OF A NONSURFACTANT PARENTERAL FORMULATION OF MICONAZOLE BY THE USE OF CYCLODEXTRINS

Miconazole is an antimycotic drug exhibiting a very poor water solubil ity(< 1.03 mu g/ml). It has been shown that cyclodextrins (CDs) are ab le to form inclusion complexes with miconazole and that they are able to increase its aqueous solubility. Miconazole is a weak base whose so lubility depends of the pH. The purpose of this study was to investiga te the influence of both CDs and different acids on the solubility of miconazole. It was found that a synergistic effect existed between CDs and different acids. The combination of hydroxypropyl-beta CD (HP-bet a CD) (100 mM) or sulfobutylether 7-beta CD (SBE7-beta CD) (50 mM) and lactic acid (50 mM) allowed to dissolve more than 10 mg of miconazole per mi. NMR studies confirmed the formation of an inclusion complex m iconazole-CD in an acidic medium. It was also shown by the NMR studies that the complex formed was a 1:1 complex. These results demonstrate that it is possible to develop a parenteral aqueous solution of micona zole without surfactant. (C) 1998 Elsevier Science B.V. All rights res erved.