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

设计了基于RESS(超临界溶液快速膨胀)原理的超细粉末生产设备，优化了生产超细粉末的条件。以布洛芬、苯丁酮和氟比洛芬为模型药物。结果表明，布洛芬的平均粒径为2.0μm(平均粒径为2.0μm)，平均粒径为2.0μm(平均粒径为2.0℃)；苯丁酮的平均粒径为0.7μm(平均粒径为2 6 MPa，32℃)；氟比洛芬的平均粒径为1.1μm(平均粒径为2 6 Mpa，40℃)。对于布洛芬或苯基丁酮，在较高温度或较高压力下制备的布洛芬或苯基丁酮的粒径较小。相反，降低温度会使氟比洛芬体系中的粒径减小。喷嘴温度和喷雾器的喷射速度对颗粒大小也有影响。但喷嘴孔径的影响不明显，证明了超临界流体用于晶体改性的潜力。采用RESS法制备了β形式的苯基丁酮粉末样品。β形式被称为亚稳态形式，其表现出比未经处理的δ形式更好的溶解性能。超临界二氧化碳处理也形成了脱氧胆酸(DCA)的多晶型。DCA的晶型尚未见报道，因此，超临界CO_2处理是获得DCA晶型的一种特殊方法。

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.