Kawakami Kohsaku, Numa Tetsuya, Ida Yasuo
Developmental Research Laboratories, Shionogi & Company, Ltd., 12-4 Sagisu 5-chome, Fukushima-ku, Osaka 553-0002, Japan.
J Pharm Sci. 2002 Feb;91(2):417-23. doi: 10.1002/jps.10017.
The amorphous content of model drugs was evaluated by isotherm microcalorimetry. Two model drugs were employed; lactose as a hydrophilic one and erythromycin as a hydrophobic one. When amorphous lactose was loaded in a sample cell with a water vial, a sharp exothermic peak due to the crystallization was observed. When a mixture of the amorphous and the crystalline forms was loaded, the peak area of the exothermic heat flow was proportional to the amorphous content. Quantification could be done with much higher accuracy than by the X-ray powder diffraction method reported in earlier literature. When erythromycin was used as a model drug, the crystallization was not completed by water but by organic solvents, which can dissolve erythromycin. The most adequate solvent for erythromycin was acetonitrile, of which the suitability was elucidated in terms of solubility and vapor pressure. This is the first report in which the role of the vapor pressure on crystallization behavior is discussed. The time needed to obtain the crystallization peak was controlled by mixing acetonitrile with water. The strategy to obtain the crystallization peak by microcalorimetry, which enables quantification of the amorphous content with high accuracy, is discussed.
采用等温微量热法评估模型药物的无定形含量。使用了两种模型药物：乳糖作为亲水性药物，红霉素作为疏水性药物。当将无定形乳糖装入带有水瓶的样品池中时，观察到由于结晶产生的尖锐放热峰。当装入无定形和结晶形式的混合物时，放热热流的峰面积与无定形含量成正比。与早期文献报道的X射线粉末衍射法相比，定量分析的准确性更高。当使用红霉素作为模型药物时，结晶不是由水而是由可溶解红霉素的有机溶剂完成的。对红霉素最合适的溶剂是乙腈，从溶解度和蒸气压方面阐明了其适用性。这是首次讨论蒸气压对结晶行为作用的报告。通过将乙腈与水混合来控制获得结晶峰所需的时间。讨论了通过微量热法获得结晶峰的策略，该方法能够高精度地定量无定形含量。
