Micronization of Pharmaceutical Substances by Rapid Expansion of Supercritical Solutions (RESS): Experiments and Modeling
Micronization of Pharmaceutical Substances by Rapid Expansion of Supercritical Solutions (RESS): Experiments and Modeling
复制标题
通过超临界溶液快速膨胀 (RESS) 实现药物微粉化：实验和建模
DOI：
10.1002/1521-4117(200211)19:5
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发表时间：
2002
影响因子：
2.7
通讯作者：
K. Schaber
中科院分区：
文献类型：
--
作者：
M. Türk;B. Helfgen;P. Hils;R. Lietzow;K. Schaber
越来越多的新开发的药物物质在水和有机介质中的溶解性都很差。因此，口服或注射药物的应用往往受到其低生物利用度的限制。另一种提高药物生物利用度的有前景的方法是通过超临界溶液快速膨胀（RESS）生产纳米级颗粒。我们的研究旨在更好地理解工艺条件和颗粒特性之间关系的基本物理现象。因此，进行了实验研究和数值模拟。用药物物质β-谷甾醇、灰黄霉素和布洛芬进行的RESS实验导致粒径在240±80 nm范围内。 此外，作为向静脉内应用难溶性药物的一个步骤，β-谷甾醇被用于生产水不溶性药物的水性悬浮液，其粒径小于或等于通过RESS生产到空气中的粒径。RESS模型的重点是通过喷嘴，超音速自由射流，马赫激波，和膨胀单元中的颗粒生长的流动。与实验结果的比较表明，一个很好的协议的一般趋势，但不完全匹配的测量平均粒径。
An increasing number of newly developed pharmaceutical substances are poorly soluble in both aqueous and organic media. Thus, the application of oral or injectable drugs is often limited by its low bioavailability. An alternative and promising method to improve the bioavailability of pharmaceutical agents is the production of nanoscale particles by the rapid expansion of supercritical solutions (RESS). Our research is aimed towards an improved understanding of the underlying physical phenomena of the relationship between the process conditions and the particle characteristics. Therefore, experimental investigations and numerical simulations were performed. RESS experiments with the pharmaceutical substances β-sitosterol, griseofulvin, and ibuprofen led to particle sizes in the range of 240±80 nm. In addition, as one step towards intravenous application of poorly soluble drugs, β-sitosterol was used to produce aqueous suspensions of a water-insoluble drug with a particle size smaller than or equal to those produced by RESS into air. RESS modeling is focused on the flow through the nozzle, the supersonic free jet, the mach shock, and particle growth in the expansion unit. The comparison with experimental results shows a good agreement in the general trends but does not match exactly the measured mean particle sizes.