Supercritical Fluids Research Group, School of Chemical Sciences and Engineering, The University of New South Wales, Sydney, New South Wales 2052, Australia.
Int J Pharm. 2011 Feb 28;405(1-2):169-80. doi: 10.1016/j.ijpharm.2010.11.042. Epub 2010 Dec 1.
Recently, subcritical water (SBCW: water that has been heated to a temperature between 100°C and 200°C at pressures of up to 70bar) has been used to dissolve several hydrophobic pharmaceutical compounds (Carr et al., 2010a). Furthermore, a number of active pharmaceutical ingredients (APIs) have been rapidly precipitated from SBCW solutions (Carr et al., 2010b,c). It is possible to alter the precipitate morphology by altering the processing variables; including the SBCW-API solution injection temperature and adding impurities (such as pharmaceutical excipients, e.g. lactose) to the precipitation chamber. The work presented in this article demonstrates that the morphology of pharmaceutical particles can be tuned by adding organic solvents (ethanol and methanol) to the SBCW-API solutions. Particle morphology has also been tuned by adding different pharmaceutical excipients (polyethylene glycol 400 and lactose) to the precipitation chamber. Different morphologies of pharmaceutical particles were produced, ranging from nanospheres of 60nm diameter to 5μm plate particles. Budesonide was used as the model API in this study. Two experimental products were spray dried to form dry powder products. The aerodynamic particle size of the powder was established by running the powder through an Andersen Cascade Impactor. It has been shown that the drug particles produced from the SBCW micronization process, when coupled with a spray drying process, are suitable for delivery to the lungs.
最近，亚临界水（SBCW：在 100°C 至 200°C 的温度下加热至 70bar 以下的水）已被用于溶解几种疏水性药物化合物（Carr 等人，2010a）。此外，许多活性药物成分（APIs）已从 SBCW 溶液中快速沉淀（Carr 等人，2010b，c）。通过改变加工变量，可以改变沉淀的形态；包括 SBCW-API 溶液的注入温度和向沉淀室中添加杂质（如药物赋形剂，例如乳糖）。本文介绍的工作表明，通过向 SBCW-API 溶液中添加有机溶剂（乙醇和甲醇）可以调节药物颗粒的形态。通过向沉淀室中添加不同的药物赋形剂（聚乙二醇 400 和乳糖）也可以调节颗粒形态。生产出了不同形态的药物颗粒，从 60nm 直径的纳米球到 5μm 的板状颗粒。布地奈德被用作本研究的模型 API。两种实验产品通过喷雾干燥形成干粉产品。通过将粉末通过安德森级联撞击器运行来确定粉末的空气动力学粒径。结果表明，通过 SBCW 微细化工艺生产的药物颗粒与喷雾干燥工艺结合使用，适用于肺部给药。
