Physical Stabilization of Pharmaceutical Glasses Based on Hydrogen Bond Reorganization under Sub-Tg Temperature

详细信息    查看全文

• 作者：Satoshi Tominaka ; Kohsaku KawakamiMayuko Fukushima ; Aoi Miyazaki
• 刊名：Molecular Pharmaceutics
• 出版年：2017
• 出版时间：January 3, 2017
• 年：2017
• 卷：14
• 期：1
• 页码：264-273
• 全文大小：608K
• ISSN：1543-8392

文摘

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_g) on physical stability, and found that the sub-T_g 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_g annealing originated from strengthened hydrogen bonding between molecules and probably from a better local packing associated with the stronger hydrogen bonds. The sub-T_g annealing is effective as a physical stabilization strategy for some pharmaceutical molecules, which have relatively large energy barrier for nucleation.