EFFECT OF CYCLODEXTRINS ON THE PHYSICOCHEMICAL PROPERTIES AND ANTIMYCOTIC ACTIVITY OF CLOTRIMAZOLE

Clotrimazole is a lipophilic drug of an antimycotic action used both l ocally and systemically. Improvement of solubility and release rate of the clotrimazole is therefore essential for a rapid antimycotic activ ity. Hence, the effect of cyclodextrins (CDs) on the physicochemical p roperties and antimycotic activity of clotrimazole was studied. Inclus ion complexation of clotrimazole with alpha-, beta- and DM-beta-CD was assessed by solubility method, microbiological assay, differential sc anning calorimetry (DSC) and powder X-ray diffractometry. The solubili ty of clotrimazole was increased markedly with DM-beta-CD, among the s tudied CDs, showing A(N)-type phase solubility diagram. The antimycoti c activity of clotrimazole against Candida albicans (C. albicans) was improved as measured for the solubilized amounts of clotrimazole taken from the phase solubility diagrams with CDs. DSC curve of coevaporate of clotrimazole with DM-beta-CD showed almost no peak in the transiti on region of clotrimazole which could be attributed to the complex for mation. Moreover, powder X-ray diffraction pattern of coevaporate of c lotrimazole with DM-beta-CD gave new crystalline diffraction pattern w hich confirmed the DSC results of inclusion complexation between clotr imazole and DM-beta-CD. The coevaporates of clotrimazole with CDs show ed superior antimycotic activity against C. albicans than the physical mixtures and drug alone, respectively. The largest inhibition zone of growth of C. albicans was obtained in the case of inclusion complex o f clotrimazole with DM-beta-CD. The coevaporate of clotrimazole with D M-beta-CD showed higher dissolution rate in good correlation with the solubility data, and these reflect the higher antimycotic activity by rapid diffusion through agar medium. Both physical mixture and inclusi on complex of clotrimazole with DM-beta-CD were formulated as efferves cent vaginal tablets they found to possess an excellent antimycotic ac tivity. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.