Kim Min-Soo, Kim Jeong-Soo, Hwang Sung-Joo
Center for Nanotechnology-Based New Drug Dosage Form, College of Pharmacy, Chungnam National University, 220 Gung-dong, Yuseong-gu, Daejeon 305-764, Republic of Korea.
Chem Pharm Bull (Tokyo). 2010 Feb;58(2):230-3. doi: 10.1248/cpb.58.230.
The aim of this study was to improve wettability and dissolution rate of a poorly water-soluble drug, cilostazol, using the supercritical antisolvent (SAS) process. The solid state of particles precipitated from dichloromethane containing additives, including poloxamer 188, poloxamer 407, TPGS 1000, Gelucire 44/14 and Gelucire 50/13, in supercritical CO(2) medium were characterized by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), FT-IR, particle size analysis, contact angle, and dissolution. Interestingly, the morphology of SAS particles processed with TPGS 1000, Gelucire 44/14 and Gelucire 50/13 changed to plate- or leaflet-shaped. Furthermore, the particle sizes of cilostazol processed with Gelucire 44/14 and Gelucire 50/13 were increased compared to cilostazol processed without additives. Poloxamer 188 and poloxamer 407 were superior in increasing the dissolution rate due to decreased particle size, the resulting increased surface area, and improved wettability. Micronization with the supercritical antisolvent process resulted in a significant decrease in mean particle size, and wettability of cilostazol was increased by using small amounts of hydrophilic additives.
本研究的目的是使用超临界抗溶剂（SAS）工艺提高难溶性药物西洛他唑的润湿性和溶解速率。通过差示扫描量热法（DSC）、粉末X射线衍射（PXRD）、傅里叶变换红外光谱（FT-IR）、粒度分析、接触角和溶出度等方法对在超临界CO₂介质中从含有泊洛沙姆188、泊洛沙姆407、TPGS 1000、Gelucire 44/14和Gelucire 50/13等添加剂的二氯甲烷中沉淀出的颗粒的固态进行了表征。有趣的是，用TPGS 1000、Gelucire 44/14和Gelucire 50/13处理的SAS颗粒的形态变为片状或小叶状。此外，与未添加添加剂处理的西洛他唑相比，用Gelucire 44/14和Gelucire 50/13处理的西洛他唑的粒径增大。泊洛沙姆188和泊洛沙姆407在提高溶解速率方面表现优异，这是由于粒径减小、表面积增大以及润湿性改善所致。用超临界抗溶剂工艺进行微粉化导致平均粒径显著减小，并且通过使用少量亲水性添加剂提高了西洛他唑的润湿性。
