Mady Fatma M, Farghaly Aly Usama
Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Taibah University, Medina, Saudi Arabia.
Department of Pharmaceutics, Faculty of Pharmacy, Minia University, Minia, Egypt.
Drug Des Devel Ther. 2017 Jun 7;11:1681-1692. doi: 10.2147/DDDT.S135084. eCollection 2017.
Finasteride (FIN) is a Class II candidate of the Biopharmaceutics Classification System (BCS). The lipophilic cavity of cyclodextrins (CyDs) enables it to construct a non-covalent inclusion complex with different insoluble drugs. Only β-cyclodextrin (β-CyD) and hydroxypropyl-β-CyD (HP-β-CyD) have been previously examined with FIN. This study aimed to investigate the consistence of FIN with different kinds of β-CyDs, including dimethyl-β-cyclodextrin (DM-β-CyD), carboxymethyl-β-cyclodextrin (CM-β-CyD), HP-β-CyD, sulfobutyl ether-β-cyclodextrin (SBE-β-CyD), and β-CyD, by the coprecipitation method. The resultant inclusion systems were characterized by differential scanning calorimetry, infrared spectroscopy, X-ray diffractometry, and dissolution studies. Moreover, molecular docking for the selected inclusion systems was carried out to explore the suitable arrangements of FIN in the cavity of β-CyD or its derivatives. The results suggested that the DM-β-CyD inclusion system gave the higher complexation efficiency for improvement in solubility of FIN and hence enhancement of its bioavailability. Pharmacokinetic parameters displayed a higher absorption rate and higher area under the curve of the FIN/DM-β-CyD inclusion complex when compared with the drug alone, which indicates an improvement in the absorption and bioavailability of FIN in the DM-β-CyD inclusion system.
非那雄胺（FIN）是生物药剂学分类系统（BCS）中的II类候选药物。环糊精（CyDs）的亲脂性空腔使其能够与不同的难溶性药物构建非共价包合物。此前仅对β-环糊精（β-CyD）和羟丙基-β-环糊精（HP-β-CyD）与非那雄胺进行过研究。本研究旨在通过共沉淀法研究非那雄胺与不同种类的β-环糊精，包括二甲基-β-环糊精（DM-β-CyD）、羧甲基-β-环糊精（CM-β-CyD）、HP-β-CyD、磺丁基醚-β-环糊精（SBE-β-CyD）和β-CyD的相容性。通过差示扫描量热法、红外光谱法、X射线衍射法和溶出度研究对所得包合物体系进行表征。此外，对所选包合物体系进行分子对接，以探索非那雄胺在β-环糊精或其衍生物空腔中的合适排列方式。结果表明，DM-β-CyD包合物体系对提高非那雄胺的溶解度具有更高的络合效率，从而提高其生物利用度。与单独的药物相比，药代动力学参数显示FIN/DM-β-CyD包合物的吸收速率更高，曲线下面积更大，这表明在DM-β-CyD包合物体系中非那雄胺的吸收和生物利用度得到了改善。
