title: Enhanced bioavailability of poorly water-soluble clotrimazole by inclusion with beta-cyclodextrin.
abstract: Clotrimazole, a poorly water-soluble antimycotic agent, is a promising agent for various diseases including cancer and sickle cell anemia. To improve the oral bioavailability of clotrimazole, the inclusion compound of clotrimazole with beta-cyclodextrin was prepared by spray-drying method and characterized by phase solubility, differential scanning calorimetry and dissolution. Furthermore, the pharmacokinetics after oral administration in rats was then performed compared with clotrimazole powder. The solubility of clotrimazole increased linearly as a function of beta-cyclodextrin concentration, resulting in A(L) type phase solubility diagram which revealed a formation of inclusion compound in a molar ratio of 1:2, with the apparent association constant of 230.2 M(-1). The dissolution rate of clotrimazole in the inclusion compound increased greatly compared to clotrimazole powder in pH 7.4 phosphate buffer solution. The inclusion compound gave significantly higher initial plasma concentrations, Cmax and AUC of clotrimazole than did clotrimazole powder when they were administered as suspension form, indicating that the drug from inclusion compound could be more orally absorbed in rats. Thus, the oral bioavailability of clotrimazole could be improved markedly by inclusion complexation, possibly due to an increased dissolution rate.
authors: College of Pharmacy, Yeungnam University, Gyongsan 712-749, Korea.
authors: Balakrishnan
authors: B
authors: Prabagar
authors: Bong-Kyu
authors: BK
authors: Yoo
authors: Jong-Soo
authors: JS
authors: Woo
authors: Jung-Ae
authors: JA
authors: Kim
authors: Jong-Dal
authors: JD
authors: Rhee
authors: Ming Guan
authors: MG
authors: Piao
authors: Han-Gon
authors: HG
authors: Choi
authors: Chul Soon
authors: CS
authors: Yong
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000935:Antifungal Agents / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics*; D001682:Biological Availability; D003022:Clotrimazole / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D014867:Water / Q000737:chemistry*; D047392:beta-Cyclodextrins / Q000737:chemistry*
chemical_list: D000935:Antifungal Agents; D047392:beta-Cyclodextrins; D014867:Water; D003022:Clotrimazole; C031215:betadex