INCLUSION COMPLEXES OF TOLNAFTATE WITH BETA-CYCLODEXTRIN AND HYDROXYPROPYL-BETA-CYCLODEXTRIN

Tolnaftate, an antifungal agent, was found to form inclusion complexes with both beta-cyclodextrin (beta-CD) and hydroxypropyl beta-cyclodex trins (HPBCDs) with two different degrees of substitution [HPBCD(A)-8% and HPBCD(B)-3%]. Complex formation in the solution state was studied using phase solubility and spectral shift methods. Solid complexes we re prepared by the coprecipitation method. Solubilities and dissolutio n rates were determined for each solid complex, its corresponding phys ical mixture, and free drug. The increase in solubility of tolnaftate with added HPBCD was found to be significantly greater than with added beta-CD. For both HPBCD(A) and HPBCD(B), over the concentration range 0-0.05 M 1:1 complexes with stability constants of 1460 +/- 139 M(-1) and 1860 +/- 165 M(-1) were observed, respectively. Over the beta-CD concentration range 0-0.02 M, a 1:1 complex with a stability constant of 1190 +/- 105 M(-1) was observed. At higher HPBCD concentrations, th e increase in solubility was observed to show a positive deviation fro m linearity (type Ap phase diagram). Using the spectral method, in a 2 5% v/v methanol in water system, the stability constants were determin ed to be 1020 +/- 150 M(-1) 1110 +/- 120 M(-1) and 1100 +/- 260 M(-1) for HPBCD(A), HPBCD(B) and beta-CD, respectively. The solid complexes prepared showed improved dissolution over physical mixtures and free d rug.