Mo. Ahmed et al., EFFECT OF CYCLODEXTRINS ON THE PHYSICOCHEMICAL PROPERTIES AND ANTIMYCOTIC ACTIVITY OF CLOTRIMAZOLE, International journal of pharmaceutics, 171(1), 1998, pp. 111-121
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.