Kondo Masahiro, Niwa Toshiyuki, Danjo Kazumi
Faculty of Pharmacy, Meijo University, Nagoya, Japan.
Yakugaku Zasshi. 2011;131(5):711-9. doi: 10.1248/yakushi.131.711.
A spray freeze drying (SFD) method, using a spray nozzle, liquid N(2) and a lyophilizer, was developed to prepare composite particles of a poorly water-soluble drug. The resultant particles were found to have a porous structure. The purpose of the present research was to prepare a sustained release formulation using the SFD technique. Tolbutamide (TBM)and Eudragit S were used as model drugs and pH-dependent carrier, respectively. Eudragit S is a polymer that is soluble at or above pH 7.0. Morphological evaluation of the composite particles revealed that they had a porous structure with a significantly larger specific surface area than bulk TBM. The physicochemical properties of the particles were found to be dependent on the drug to carrier ratio, with the crystallinity of the TBM decreasing as the proportion of Eudragit S increased. Dissolution tests in solutions of pH 1.2 and pH 6.8 showed that the release profiles of TBM from the SFD composite particles were improved compared to bulk TBM, through the use of the pH-dependent carrier. On the other hand, following compression of the composite particles, sustained release was observed in a solution of pH 6.8, whereas almost no dissolution occurred in a solution of pH 1.2.
开发了一种喷雾冷冻干燥（SFD）方法，使用喷雾喷嘴、液氮和冻干机来制备难溶性药物的复合颗粒。发现所得颗粒具有多孔结构。本研究的目的是使用SFD技术制备缓释制剂。分别使用甲苯磺丁脲（TBM）和尤特奇S作为模型药物和pH依赖性载体。尤特奇S是一种在pH 7.0或以上可溶的聚合物。对复合颗粒的形态学评估表明，它们具有多孔结构，比块状TBM的比表面积大得多。发现颗粒的物理化学性质取决于药物与载体的比例，随着尤特奇S比例的增加，TBM的结晶度降低。在pH 1.2和pH 6.8溶液中的溶出试验表明，与块状TBM相比，通过使用pH依赖性载体，TBM从SFD复合颗粒中的释放曲线得到了改善。另一方面，复合颗粒压缩后，在pH 6.8的溶液中观察到缓释，而在pH 1.2的溶液中几乎没有溶解。
