Tominaka Satoshi, Kawakami Kohsaku, Fukushima Mayuko, Miyazaki Aoi
International Center for Materials Nanoarchitectonics, National Institute for Materials Science , 1-1 Namiki, Tsukuba, Ibaraki 305-0044, Japan.
Mol Pharm. 2017 Jan 3;14(1):264-273. doi: 10.1021/acs.molpharmaceut.6b00866. Epub 2016 Dec 2.
Amorphous solid dispersions (ASDs) play a key role in the pharmaceutical industry through the use of high-energy amorphous state to improve solubility of pharmaceutical agents. Understanding the physical stability of pharmaceutical glasses is of great importance for their successful development. We focused on the anti-HIV agent, ritonavir (RTV), and investigated the influence of annealing at temperatures below the glass transition temperature (sub-T) on physical stability, and found that the sub-T annealing effectively stabilized RTV glasses. Through the atomic structure analyses using X-ray pair distribution functions and infrared spectroscopy, we ascertained that this fascinating effect of the sub-T annealing originated from strengthened hydrogen bonding between molecules and probably from a better local packing associated with the stronger hydrogen bonds. The sub-T annealing is effective as a physical stabilization strategy for some pharmaceutical molecules, which have relatively large energy barrier for nucleation.
无定形固体分散体（ASDs）通过利用高能无定形态来提高药物的溶解度，在制药行业中发挥着关键作用。了解药用玻璃的物理稳定性对其成功开发至关重要。我们聚焦于抗HIV药物利托那韦（RTV），研究了在低于玻璃化转变温度（亚T）下退火对物理稳定性的影响，发现亚T退火有效地稳定了RTV玻璃。通过使用X射线对分布函数和红外光谱进行原子结构分析，我们确定亚T退火这种引人注目的效果源于分子间氢键的增强，可能还源于与更强氢键相关的更好的局部堆积。对于一些成核能量垒相对较大的药物分子，亚T退火作为一种物理稳定策略是有效的。
