Department of Pharmaceutics, School of Pharmaceutical Sciences, Central South University, Changsha, PR China.
Drug Dev Ind Pharm. 2009 Jul;35(7):808-13. doi: 10.1080/03639040802612944.
Fluorofenidone is a novel antifibrotic drug and its aqueous solubility is low.
This study was to prepare and characterize inclusion complexes of fluorofenidone (AKF-PD) with beta-cyclodextrin (beta-CD) and hydroxypropyl-beta-cyclodextrin (HP-beta-CD).
The AKF-PD/cyclodextrins (CDs) inclusion complexes were prepared by coprecipitation and freeze-drying, respectively. The solubility enhancement of AKF-PD was evaluated by phase solubility method. Inclusion complexation in solid phase was studied by X-ray diffraction (XRD) and differential thermal analysis (DTA). The dissolution profiles of AKF-PD/CDs inclusion complexes were investigated and compared with those of their physical mixtures and AKF-PD alone.
The phase solubility diagrams of AKF-PD with beta-CD and HP-beta-CD were of A(L)-types, and the solubility of AKF-PD could be increased by 51.5% for beta-CD at 0.014 M and 794.0% for HP-beta-CD at 0.254 M. The results from XRD and DTA suggested that AKF-PD could form inclusion complex with beta-CD or HP-beta-CD. The dissolution rate of AKF-PD from the inclusion complexes was much more rapid than AKF-PD alone.
The formulation of AKF-PD/CDs inclusion complexes showed superior performance in improving dissolution properties of AKF-PD.
氟苯尼考是一种新型抗纤维化药物，其水溶性较低。
本研究旨在制备并表征氟苯尼考（AKF-PD）与β-环糊精（β-CD）和羟丙基-β-环糊精（HP-β-CD）的包合物。
分别采用共沉淀法和冷冻干燥法制备 AKF-PD/环糊精（CDs）包合物。采用相溶解度法评价 AKF-PD 的增溶效果。通过 X 射线衍射（XRD）和差示热分析（DTA）研究固态包合情况。考察并比较了 AKF-PD/CDs 包合物及其物理混合物和 AKF-PD 原料药的溶出曲线。
AKF-PD 与β-CD 和 HP-β-CD 的相溶解度图均为 A（L）型，β-CD 在 0.014 M 时，AKF-PD 的溶解度可增加 51.5%，HP-β-CD 在 0.254 M 时，AKF-PD 的溶解度可增加 794.0%。XRD 和 DTA 结果表明，AKF-PD 可与β-CD 或 HP-β-CD 形成包合物。包合物中 AKF-PD 的溶出速率明显快于 AKF-PD 原料药。
AKF-PD/CDs 包合物制剂在改善 AKF-PD 的溶解性能方面表现出优异的性能。
