Inclusion complex of amiodarone hydrochloride with cyclodextrins: preparation, characterization and dissolution rate evaluation

ABSTRACT This study aimed to improve the water solubility of amiodarone hydrochloride (AMH) via inclusion complexes with β-cyclodextrin, methyl-β-cyclodextrin and 2-hydroxypropyl-β-cyclodextrin. Inclusion complexes were developed by physical mixture, coevaporation, spray-drying and freeze-drying. Solid state analysis was performed using X-ray powder diffraction, differential scanning calorimetry and scanning electronic microscopy. Thermodynamic studies demonstrate that the inclusion complexes of drug into different cyclodextrins were an exothermic process that occurred spontaneously. Water solubility and drug dissolution rates were significantly increased after the formation of inclusion complexes with the cyclodextrins evaluated in relation to the physical mixture and pure drug. The present study provides useful information for the potential application of complexation with amiodarone HCl. This may be a good strategy for the development of solid pharmaceutical dosage forms.

摘要
本研究旨在通过与β-环糊精（β-cyclodextrin）、甲基-β-环糊精（methyl-β-cyclodextrin）以及2-羟丙基-β-环糊精（2-hydroxypropyl-β-cyclodextrin）形成包合物，提升盐酸胺碘酮（amiodarone hydrochloride, AMH）的水溶性。研究采用物理混合法、共蒸发法、喷雾干燥法与冷冻干燥法制备包合物，通过X射线粉末衍射（X-ray powder diffraction）、差示扫描量热法（differential scanning calorimetry）以及扫描电子显微镜（scanning electronic microscopy）开展固态表征分析。热力学研究结果表明，药物与不同环糊精形成包合物的过程为自发进行的放热过程。相较于物理混合物与纯药物，经环糊精包合后，药物的水溶性与溶出速率均得到显著提升。本研究为盐酸胺碘酮包合技术的潜在应用提供了有价值的参考依据，或可为固体制剂的开发提供优良策略。