Characterization, stability, and pharmacokinetics of sibutramine/beta-cyclodextrin inclusion complex

Abstract

beta-Cyclodextrin (beta-CD) is widely used to increase the stability, solubility, and bioavailability of poorly soluble drugs because of the appropriate size of its cavity. Sibutramine is a neurotransmitter reuptake inhibitor that has been investigated as an oral anorexiant. Here we report the complexation of sibutramine base with beta-CD and the stability, dissolution, and pharmacokinetic properties of the sibutramine/CD complex. The formation of sibutramine/beta-CD inclusion complexes is confirmed using differential scanning calorimetry, X-ray diffractometry, and H-1 nuclear magnetic resonance. The thermal and photochemical stability of sibutramine is significantly improved by the complexation with beta-CD, and the pharmacokinetic parameters (e.g., the plasma concentration, area under the curve, and maximum concentration of two active metabolites) for humans are comparable with those of the commercialized standard product (Reductil (R)). Our study suggests that sibutramine/beta-CD complexation can be of great use to increase the stability and biological efficacy of sibutramine base. (C) 2012 The Korean Society of Industrial and Engineering Chemistry. Published by Elsevier BM. All rights reserved.