A Strategy for Co-former Selection to Design Stable Co-amorphous Formations Based on Physicochemical Properties of Non-steroidal Inflammatory Drugs

作者：Ueda Hiroshi^*; Muranushi Noriyuki; Sakuma Satoshi; Ida Yasuo; Endoh Takeshi; Kadota Kazunori; Tozuka Yuichi

来源：Pharmaceutical Research, 2016, 33(4): 1018-1029.

DOI：10.1007/s11095-015-1848-2

• amorphous
• co-amorphous
• crystallization
• glass transition temperature
• intermolecular interaction
• multivariate analysis

This study aimed to investigate the physicochemical factors contributing to stable co-amorphous formations and to design a co-former selection strategy.
Non-steroidal inflammatory drugs were used as main components and/or co-formers. Physical mixtures of the materials were melted. Co-amorphization was characterized by the inhibition effect of the co-former on crystallization of the main component from the undercooled melt. The contribution of physicochemical factors to the co-amorphous formation was analyzed by multivariate analysis. Co-amorphous samples prepared by melting were subjected to thermal and spectroscopic analyses and the isothermal crystallization test.
Naproxen (NAP) was employed as the main component having a rapid crystallization tendency. Some materials used as the co-former inhibited the crystallization of amorphous NAP; decreasing melting temperatures of the components was an indicator of co-amorphization. The contribution of some physicochemical features (e.g., crystallization tendency, glass transition temperature (Tg)/melting temperature and molecular flexibility) of the co-formers to a co-amorphous formation was suggested by multivariate analysis. Deviation of the glass transition temperature from the theoretical value and changes in the infrared spectra of the co-amorphous samples were correlated with intermolecular interaction. The crystallization behaviors of the co-amorphous samples depended on their Tg.
The results showed a relationship between stable co-amorphous formation and the physicochemical features of the components, which should inform efficient co-former selection to design stable co-amorphous formations.

• 出版日期2016-4