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

• Published in: Archives of pharmacal research 2012, 35(7), , pp.1169-1175
• Main Authors: Balakrishnan, Prabagar, Song, Chung Kil, Cho, Hyun-Jong, Yang, Su-Geun, Kim, Dae Duk, Yong, Chul Soon, Choi, Han-Gon
• Format: Article
• Language: English
• Subjects: Administration, Rectal; Animals; Antifungal Agents - administration & dosage; Antifungal Agents - blood; Antifungal Agents - chemistry; Antifungal Agents - pharmacokinetics; beta-Cyclodextrins - chemistry; Biological Availability; Calorimetry, Differential Scanning; Chemistry, Pharmaceutical; Clotrimazole - administration & dosage; Clotrimazole - blood; Clotrimazole - chemistry; Clotrimazole - pharmacokinetics; Drug Carriers; Hydrophobic and Hydrophilic Interactions; Male; Medicine; Models, Chemical; Pharmacology/Toxicology; Pharmacy; Poloxamer - chemistry; Powder Diffraction; Propylene Glycol - chemistry; Rats; Rats, Sprague-Dawley; Solubility; Suppositories; Technology, Pharmaceutical - methods; 약학
• ISSN: 0253-6269; 1976-3786
• DOI: 10.1007/s12272-012-0707-5

To study the effect of β-cyclodextrin (βCD) inclusion complex on the bioavailability of clotrimazole from poloxamer-based suppository, formulations composed of P 188, propylene glycol and different molar ratio of clotrimazole-βCD 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 βCD (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 βCD, 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 βCD molar ratio (F1) could be a potential suppository formulation to increase the bioavailability of hydrophobic drugs such as clotrimazole.