Onyeji C O, Omoruyi S I, Oladimeji F A
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Obafemi Awolowo University, Ile-Ife, Nigeria.
Pharmazie. 2007 Nov;62(11):858-63.
Halofantrine (HF) is a poorly water-soluble antimalarial drug with low bioavailability. Complex formation of HF.HCl and 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CD) in aqueous solution and in solid state as well as the possibility of improving the solubility and dissolution rate of the drug though complexation with the cyclodextrin were investigated. Phase-solubility profile indicated that the solubility of the drug was significantly increased in the presence of HP-beta-CD and was classified as AL-type, indicating 1:1 stoichiometric inclusion complexes and an apparent stability constant value of 2300 M(-1). Solid inclusion complexes of HF, HCl and the cyclodextrin at 1:1 molar ratios were prepared by physical mixture, kneading, co-evaporation and freeze-drying methods and characterized by X-ray diffraction and Infra-red spectroscopy. The solubility and dissolution rates of HF.HCl from the complexes were determined and found to be dependent on the preparation method of the complexes. Dissolution profile of the drug was markedly enhanced by complex formation with the cyclodextrin and the product prepared by the freeze-drying method exhibited the most superior dissolution properties compared to the other methods used in this study. The results suggest that the complexation of HF.HCl with HP-beta-CD could improve therapeutic efficacy of the drug though enhanced absorption expected from increased drug dissolution.
卤泛群（HF）是一种水溶性差、生物利用度低的抗疟药物。研究了HF.HCl与2-羟丙基-β-环糊精（HP-β-CD）在水溶液和固态中的络合物形成，以及通过与环糊精络合提高药物溶解度和溶解速率的可能性。相溶解度曲线表明，在HP-β-CD存在下药物的溶解度显著增加，属于AL型，表明形成了化学计量比为1:1的包合物，表观稳定常数为2300 M(-1)。通过物理混合、捏合、共蒸发和冷冻干燥法制备了摩尔比为1:1的HF、HCl与环糊精的固体包合物，并通过X射线衍射和红外光谱进行了表征。测定了络合物中HF.HCl的溶解度和溶解速率，发现其取决于络合物的制备方法。与环糊精形成络合物后，药物的溶出曲线显著增强，与本研究中使用的其他方法相比，冷冻干燥法制备的产品表现出最优异的溶解性能。结果表明，HF.HCl与HP-β-CD络合可通过提高药物溶解预期的吸收增强来提高药物的治疗效果。
