Lu Rong, Liu Shan, Wang Qilin, Li Xia
Pharmazie. 2015 Dec;70(12):791-7.
This study aimed to develop a dry suspension formulation of raloxifene (RLX) using its HP-β-cyclodextrin inclusion complexes to enhance the oral bioavailability. Dry suspensions loading RLX/HP-β-cyclodextrin inclusion complexes (RLX-HICs) were prepared by solvent evaporation followed by a standard wet granulation process. The inclusion complexes were characterized by scanning electron microscopy, differential scanning calorimetry, and Fourier transform infrared spectroscopy. The features of dry suspensions such as dispersibility, flowability and dissolution were compared with conventional suspensions. Dry suspensions containing RLX-HICs dramatically increased the dissolution of RLX. Pharmacokinetic studies in rats showed that dry suspensions with RLX-HICs significantly enhanced the oral bioavailabilities of RLX. The absolute and relative bioavailabilities were up to 13.04% and 413.97% compared with the solution formulation (i.v.) and conventional suspensions (i.g.), respectively. The bioavailability improvement for dry suspensions with RLX-HICs can be attributed to improved dissolution and physiochemical properties of RLX, by which the overall absorption was enhanced. Dry suspensions prepared from RLX-HICs may be an attractive formulation for the oral delivery of RLX.
本研究旨在利用雷洛昔芬（RLX）的羟丙基-β-环糊精包合物开发一种雷洛昔芬干混悬剂，以提高其口服生物利用度。通过溶剂蒸发，随后采用标准湿法制粒工艺制备了负载RLX/羟丙基-β-环糊精包合物（RLX-HICs）的干混悬剂。通过扫描电子显微镜、差示扫描量热法和傅里叶变换红外光谱对包合物进行了表征。将干混悬剂的分散性、流动性和溶解性等特性与传统混悬剂进行了比较。含有RLX-HICs的干混悬剂显著提高了RLX的溶出度。大鼠体内药代动力学研究表明，含有RLX-HICs的干混悬剂显著提高了RLX的口服生物利用度。与溶液制剂（静脉注射）和传统混悬剂（灌胃）相比，绝对生物利用度和相对生物利用度分别高达13.04%和413.97%。含有RLX-HICs的干混悬剂生物利用度的提高可归因于RLX溶出度和理化性质的改善，从而增强了整体吸收。由RLX-HICs制备的干混悬剂可能是一种有吸引力的RLX口服给药制剂。
