2002 Fiscal Year Final Research Report Summary
Characterization for Pharmaceutical Solid Dispersion Prepared by means of Supercritical Carbon Dioxide
| Project/Area Number |
12672085
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Physical pharmacy
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| Research Institution | University of Yamanashi, Faculty of Medicine (2002)
Chiba University (2000-2001) |
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Principal Investigator |
OGUCHI Toshio University of Yamanashi, Faculty of Medicine, Professor, 医学部, 教授 (30169255)
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| Co-Investigator(Kenkyū-buntansha) |
TOZUKA Yuichi Chiba University, Graduate School of Pharm. Sci., Res. Assoc., 大学院・薬学研究院, 助手 (50312963)
YAMAMOTO Keiji Chiba University, Graduate School of Pharm. Sci., Professor, 大学院・薬学研究院, 教授 (50110341)
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| Project Period (FY) |
2000 – 2002
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| Keywords | Supercritical Fluid / Particle Design / Micronisation / Crystallinity / Particle Size |
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| Research Abstract |
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.
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