title: Inclusion complex effect on the bioavailability of clotrimazole from poloxamer-based solid suppository.
abstract: 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.
authors.affiliation: College of Pharmacy, Yeungnam University, Gyongsan 712-749, Korea.
authors.forename: Prabagar
authors.initials: P
authors.lastname: Balakrishnan
authors.forename: Chung Kil
authors.initials: CK
authors.lastname: Song
authors.forename: Hyun-Jong
authors.initials: HJ
authors.lastname: Cho
authors.forename: Su-Geun
authors.initials: SG
authors.lastname: Yang
authors.forename: Dae Duk
authors.initials: DD
authors.lastname: Kim
authors.forename: Chul Soon
authors.initials: CS
authors.lastname: Yong
authors.forename: Han-Gon
authors.initials: HG
authors.lastname: Choi
mesh_terms: D000285:Administration, Rectal; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D001682:Biological Availability; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D003022:Clotrimazole / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D004337:Drug Carriers; D057927:Hydrophobic and Hydrophilic Interactions; D008297:Male; D008956:Models, Chemical; D020442:Poloxamer / Q000737:chemistry*; D033362:Powder Diffraction; D019946:Propylene Glycol / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013488:Suppositories; D013678:Technology, Pharmaceutical / Q000379:methods; D047392:beta-Cyclodextrins / Q000737:chemistry*
chemical_list: D000935:Antifungal Agents; D004337:Drug Carriers; D013488:Suppositories; D047392:beta-Cyclodextrins; D020442:Poloxamer; D019946:Propylene Glycol; D003022:Clotrimazole