Inclusion complex effect on the bioavailability of clotrimazole from poloxamer-based solid suppository

Abstract

To study the effect of beta-cyclodextrin (beta CD) inclusion complex on the bioavailability of clotrimazole from poloxamer-based suppository, formulations composed of P 188, propylene glycol and different molar ratio of clotrimazole-beta CD inclusion complex were prepared. Clotrimazole (1%) has been formulated in a suppository using the thermo sensitive polymer P188 (70%) together with propylene glycol (30%). To increase its aqueous solubility, clotrimazole was incorporated as its inclusion complex at various molar ratios with beta CD (1:0.25, 1:0.5, 1:1, and 1:2). The inclusion complex was characterized by differential scanning calorimetry (DSC), XRD and phase solubility studies. It was observed that the complexation with beta CD, particularly at high molar ratio (F3 (1:1) and F4 (1:2)) decreased the release profile of clotrimazole considerably. However, suppositories containing inclusion complex at low molar ratio (F1 (1:0.25) and F2 (1:0.5)) showed excellent release profile compared to control formulation. In vivo study in rats at 15 mg/Kg dose showed that the F1 and F2 (82.39 +/- 15.40 and 67.05 +/- 8.79, respectively) significantly increased the AUC compared to that of F3 (41.48 +/- 11.51), F4 (23.34 +/- 8.37) and control (46.7 +/- 7.87) suppositories. Thus, the suppositories containing inclusion complexes prepared at low drug to beta CD molar ratio (F1) could be a potential suppository formulation to increase the bioavailability of hydrophobic drugs such as clotrimazole.