Formation of submicron poorly water-soluble drugs by rapid expansion of supercritical solution (RESS): Results for Naproxen
Formation of submicron poorly water-soluble drugs by rapid expansion of supercritical solution (RESS): Results for Naproxen
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DOI：
10.1016/j.supflu.2010.09.023
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发表时间：
2010-12-01
影响因子：
3.9
通讯作者：
Bolten, Dennis
中科院分区：
文献类型：
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作者：
Tuerk, Michael;Bolten, Dennis
大量的研究结果表明，超临界流体的特殊性质可以方便地用于形成亚微米颗粒。在药物物质的情况下，药物在生物介质中的不良溶出行为和随之而来的生物利用度可以通过减小粒度而显著提高。在本文中，我们报告的应用RESS（超临界溶液的快速膨胀）和RESSAS（超临界溶液快速膨胀成水溶液），以生产亚微米颗粒的Na 2CO 3，一种水溶性差的药物。从而考察了各种工艺条件对所得产品性能的影响。实验结果表明，Na 2CO 3的RESS处理导致颗粒在0.56至0.82 μ m的范围内，其比未处理的粉末小约22倍。RESSAS实验表明，在0.4wt%PVP溶液中，药物浓度高达1g/dm（3）时，稳定的Na 2SO 4颗粒的平均直径为0.3 μ m，而在0.4wt%Tween 80溶液中膨胀产生直径为8 μ m的颗粒。此外，它表明，经处理的粉末的改善的溶解行为取决于粒度，因此增加的表面积和溶解介质的pH值。(C)2010 Elsevier BV保留所有权利。
Numerous results of multitude investigations indicate that the particular properties of supercritical fluids can be conveniently exploited for the formation of submicron particles. In case of pharmaceutical substances the poor dissolution behaviour and therewith bioavailability of drugs in biological media can be enhanced dramatically by reduction of the particle size. In this paper we report the application of RESS (Rapid Expansion of Supercritical Solutions) and RESSAS (Rapid Expansion of Supercritical Solution into Aqueous Solution) to produce submicron particles of Naproxen, a poorly water-soluble drug. Thereby the effect of various process conditions on the obtained product properties was investigated. The experimental results show, that the RESS processing of Naproxen leads to particles in the range from 0.56 to 0.82 mu m which is about 22 times smaller than the unprocessed powder. RESSAS experiments show, that stabilized Naproxen particles have an average diameter of 0.3 mu m for drug concentrations up to 1 g/dm(3) in 0.4 wt% PVP solution while expansion into a 0.4 wt% Tween (R) 80 solution produced particles 8 mu m in diameter. Furthermore, it is shown that the improved dissolution behaviour of the processed powder depends on the particle size and hence increased surface area and on the pH-value of the dissolution media. (C) 2010 Elsevier B.V. All rights reserved.