title: Preparation and Characterization of the Sulfobutylether-β-Cyclodextrin Inclusion Complex of Amiodarone Hydrochloride with Enhanced Oral Bioavailability in Fasted State.
abstract: Amiodarone hydrochloride (AMD) is used in the treatment of a wide range of cardiac tachyarrhythmias, including both ventricular fibrillation (VF) and hemodynamically unstable ventricular tachycardia (VT). The objectives of this study were to improve the solubility and bioavailability in fasted state and to reduce the food effect of AMD by producing its inclusion complex with sulfobutylether-β-cyclodextrin (SBE-β-CD). The complex was prepared through a saturated water solution combined with the freeze-drying method and then characterized by Fourier transform infrared spectroscopy, proton nuclear magnetic resonance spectroscopy, and differential scanning calorimetry. The solubilities of AMD and its complex were 0.35 and 68.62 mg/mL, respectively, and the value of the inclusion complex was significantly improved by 196-fold compared with the solubility of free AMD. The dissolution of the AMD-SBE-β-CD inclusion complex in four different dissolution media was larger than that of the commercial product. The cumulative dissolution was more than 85% in water, pH 4.5 NaAc-HAC buffer, and pH 1.2 HCl aqueous solution. Moreover, the pharmacokinetic study found that the Cmax, AUC(0-t), and AUC(0-∞)of the AMI-SBE-β-CD inclusion complex had no significant difference in fasted and fed state, which indicated that the absorption of the AMI-SBE-β-CD inclusion complex in fasted state was increased and not affected by food.
authors.affiliation: School of Pharmacy, Nanjing Tech University, 5th Mofan Road, Nanjing, 21009, China.
authors.forename: Dandan
authors.initials: D
authors.lastname: Wang
authors.affiliation: School of Pharmacy, Nanjing Tech University, 5th Mofan Road, Nanjing, 21009, China. Yilianwdd@163.com.
authors.forename: Guoguang
authors.initials: G
authors.lastname: Chen
authors.affiliation: School of Pharmacy, Nanjing Tech University, 5th Mofan Road, Nanjing, 21009, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Ren
mesh_terms: D000638:Amiodarone / Q000737:chemistry / Q000493:pharmacokinetics; D000889:Anti-Arrhythmia Agents / Q000737:chemistry / Q000493:pharmacokinetics; D001682:Biological Availability; D002152:Calorimetry, Differential Scanning / Q000379:methods; D004339:Drug Compounding / Q000379:methods; D018565:Food-Drug Interactions; D005612:Freeze Drying / Q000379:methods; D006801:Humans; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared / Q000379:methods; D014961:X-Ray Diffraction / Q000379:methods; D047392:beta-Cyclodextrins / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: D000889:Anti-Arrhythmia Agents; D047392:beta-Cyclodextrins; C093196:SBE4-beta-cyclodextrin; D000638:Amiodarone
keywords: amiodarone hydrochloride; bioavailability; characterization; food effect; inclusion complex; solubility