Hiroshi Ueda1,2, Noriyuki Muranushi3, Satoshi Sakuma3, Yasuo Ida4, Takeshi Endoh4, Kazunori Kadota5, Yuichi Tozuka5. 1. Physicochemical and Preformulation, Applied Chemistry and Analysis, Research Laboratory for Development, Shionogi & Co., Ltd, 3-1-1, Futaba-cho, Toyonaka-shi, Osaka, 561-0825, Japan. hiroshi.ueda@shionogi.co.jp. 2. Laboratory of Formulation Design and Pharmaceutical Technology, Osaka University of Pharmaceutical Sciences, 4-20-1, Nasahara, Takatsuki-shi, Osaka, 569-1094, Japan. hiroshi.ueda@shionogi.co.jp. 3. New Technology Department, Formulation Development Center, CMC Development Laboratories, Shionogi & Co., Ltd., 2-1-3, Kuise-Terajima, Amagasaki-shi, Hyogo, 660-0813, Japan. 4. Physicochemical and Preformulation, Applied Chemistry and Analysis, Research Laboratory for Development, Shionogi & Co., Ltd, 3-1-1, Futaba-cho, Toyonaka-shi, Osaka, 561-0825, Japan. 5. Laboratory of Formulation Design and Pharmaceutical Technology, Osaka University of Pharmaceutical Sciences, 4-20-1, Nasahara, Takatsuki-shi, Osaka, 569-1094, Japan.
Abstract
PURPOSE: This study aimed to investigate the physicochemical factors contributing to stable co-amorphous formations and to design a co-former selection strategy. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
PURPOSE: This study aimed to investigate the physicochemical factors contributing to stable co-amorphous formations and to design a co-former selection strategy. METHODS: 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. RESULTS: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. CONCLUSIONS: 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.
Authors: Péter Lajos Sóti; Katalin Bocz; Hajnalka Pataki; Zsuzsanna Eke; Attila Farkas; Geert Verreck; Éva Kiss; Pál Fekete; Tamás Vigh; István Wagner; Zsombor K Nagy; György Marosi Journal: Int J Pharm Date: 2015-08-01 Impact factor: 5.875
Authors: Jan Bevernage; Thomas Forier; Joachim Brouwers; Jan Tack; Pieter Annaert; Patrick Augustijns Journal: Mol Pharm Date: 2011-02-22 Impact factor: 4.939
Authors: Morten Allesø; Norman Chieng; Sönke Rehder; Jukka Rantanen; Thomas Rades; Jaakko Aaltonen Journal: J Control Release Date: 2009-02-10 Impact factor: 9.776