Characterization for Pharmaceutical Solid Dispersion Prepared by means of Supercritical Carbon Dioxide

设计了基于超临界溶液快速膨胀原理的超细粉体制备装置，优化了超细粉体制备条件。以布洛芬、保泰松和氟比洛芬为模型药物。结果表明，布洛芬在26 MPa、40℃下的平均粒径为2.0 μm，保泰松在26 MPa、32℃下的平均粒径为0.7 μm，氟比洛芬在26 MPa、40℃下的平均粒径为1.1 μm。布洛芬和保泰松在较高的温度和压力下制备，其粒径减小。相反，降低温度导致氟比洛芬体系的粒径减小。喷嘴温度和喷射器的喷射速率也会影响颗粒的粒径。然而，喷嘴孔径的影响并不显著。超临界流体的潜在利用的晶体改性。通过RESS过程得到β-型保泰松粉末样品。β-形式被称为亚稳态形式，其显示出优于未加工的δ-形式的溶解特性。脱氧胆酸（DCA）的多晶型物也通过使用超临界二氧化碳处理形成。DCA的多晶型未见报道，因此，SC-CO_2处理是一种获得DCA多晶型的独特方法。

The equipment based on the RESS (Rapid Expansion of Supercritical Solution) principle was designed and the condition for fine powder production was optimized. Ibuprofen, phenylbutazone and flurbiprofen were used as model drugs. Finally, fine particles with narrow size distribution were successfully obtained as follows: 2.0 μm (average particle size) for ibuprofen at 26 Mpa, 40℃; 0.7 μm for phenylbutazone at 26MPa, 32℃; 1.1 μm for flurbiprofen at 26MPa, 40℃.The temperature and pressure in the extraction unit had significant effect on the properties of powder obtained was investigated. As for ibuprofen or phenylbutazone, the particle size reduced when prepared at higher temperature or higher pressure. On contrary, lowering temperature brought reduction of particle size in the flurbiprofen system. The temperature of nozzle and ejecting rate of spraying vessel also affected on the particle size. However, the effect of the orifice diameter of the nozzle was not significant.Potent utilization of supercritical fluid for crystallographic modification was demonstrated. The phenylbutazone powdered specimen was obtained as the β-form by the RESS process. The β-form is known as a metastable form which shows superior dissolution property rather than the unprocessed δ-form. A polymorph of deoxycholic acid (DCA) was also formed by using a supercritical carbon dioxide treatment. The polymorphs of DCA have not been reported; therefore, the SC-CO_2 treatment would be a peculiar method to obtain a DCA polymorph.