Giri Bhupendra Raj, Lee Jaehyeok, Lim Dong Yu, Kim Dong Wuk
Vessel-Organ Interaction Research Center (VOICE, MRC), BK21 FOUR Community-Based Intelligent Novel Drug Discovery Education Unit, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu, South Korea.
College of Pharmacy, Dankook University, Cheon-an, South Korea.
Drug Dev Ind Pharm. 2021 Feb;47(2):319-328. doi: 10.1080/03639045.2021.1879840. Epub 2021 Feb 12.
Despite the development in novel drug delivery techniques and synthesis of multifunctional excipients, oral delivery of hydrophobic drug like docetaxel (DTX) is still challenging. The present work investigates the inclusion complexation of DTX, and dimethyl-β-cyclodextrin (DM-β-CD) to improve the solubility, dissolution and permeability of the drug. Amongst the native and modified β-cyclodextrins, DM-β-CD showed the highest solubility of DTX. Solid binary inclusion complex (IC) of DTX with DM-β-CD was prepared by solvent evaporation technique and thoroughly characterized for solubility, dissolution, permeability, scanning electron microscopy (SEM), differential scanning calorimetry (DSC), X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FT-IR) and nuclear magnetic resonance (H NMR). The aqueous solubility and dissolution rate of DTX/DM-β-CD IC were markedly increased by 76.04- and 3.55-fold compared to free DTX powder. The permeability of DTX/DM-β-CD IC showed similar absorptive permeability but decreased efflux from the absorbed DTX, compared to pure DTX. Further, physicochemical studies of IC revealed the change of crystalline state DTX to its amorphous form. Moreover, FT-IR and H NMR results indicate the formation of true inclusion complex between DTX and DM-β-CD at 1:1 molar ratio. Collectively, solid inclusion complexes prepared by spray drying method can be an effective strategy to enhance the biopharmaceutical performance of a highly hydrophobic drug DTX.
尽管新型药物递送技术不断发展，多功能辅料也得以合成，但多西他赛（DTX）这类疏水性药物的口服给药仍然具有挑战性。本研究考察了DTX与二甲基-β-环糊精（DM-β-CD）形成包合物，以提高药物的溶解度、溶出度和渗透性。在天然和改性β-环糊精中，DM-β-CD对DTX的溶解度最高。采用溶剂蒸发技术制备了DTX与DM-β-CD的固体二元包合物（IC），并对其溶解度、溶出度、渗透性、扫描电子显微镜（SEM）、差示扫描量热法（DSC）、X射线衍射（XRD）、傅里叶变换红外光谱（FT-IR）和核磁共振（H NMR）进行了全面表征。与游离DTX粉末相比，DTX/DM-β-CD IC的水溶性和溶出速率显著提高，分别提高了76.04倍和3.55倍。与纯DTX相比，DTX/DM-β-CD IC的渗透性显示出相似的吸收渗透性，但吸收的DTX的外排减少。此外，IC的物理化学研究表明DTX的晶态转变为非晶态。此外，FT-IR和H NMR结果表明DTX与DM-β-CD以1:1摩尔比形成了真正的包合物。总体而言，通过喷雾干燥法制备的固体包合物可能是提高高疏水性药物DTX生物药剂学性能的有效策略。
