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

超临界二氧化碳制备药物固体分散体的表征

基本信息

批准号：
12672085
负责人：
OGUCHI Toshio
金额：
$ 0.64万
依托单位：
University of Yamanashi, Faculty of Medicine (2002)Chiba University (2000-2001)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12672085/
关键词：
Supercritical Fluid Particle Design Micronisation Crystallinity Particle Size 補集固体分散系微細化

项目摘要

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.

设计了基于RESS（超临界溶液快速膨胀）原理的设备，并以布洛芬、保泰松和氟比洛芬为模型药物，对细粉生产条件进行了优化，最终成功获得了窄粒度分布的细颗粒。：布洛芬 2.0 μm（平均粒径），26 Mpa，40℃；保泰松 0.7 μm，26 MPa， 32℃；氟比洛芬在26MPa、40℃下为1.1μm。研究了萃取装置中的温度和压力对所得粉末的性质的显着影响，对于布洛芬或保泰松，在较高温度或更高温度下制备时粒度减小。相反，降低温度会导致氟比洛芬系统中的粒径减小，喷嘴温度和喷雾容器的喷射速率也对粒径产生影响。然而，喷嘴孔径的影响并不显着。通过RESS工艺获得了β-形式的保泰松粉末样品，证明了超临界流体的有效利用。通过使用超临界二氧化碳处理，还形成了比未加工的δ-形式更优异的溶解性能的亚稳定形式。尚未见报道；因此，SC-CO_2处理将是获得DCA多晶型物的独特方法。