title: A Strategy for Co-former Selection to Design Stable Co-amorphous Formations Based on Physicochemical Properties of Non-steroidal Inflammatory Drugs.
abstract: OBJECTIVE
  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.affiliation: 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.|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.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ueda
authors.affiliation: New Technology Department, Formulation Development Center, CMC Development Laboratories, Shionogi & Co., Ltd., 2-1-3, Kuise-Terajima, Amagasaki-shi, Hyogo, 660-0813, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Muranushi
authors.affiliation: New Technology Department, Formulation Development Center, CMC Development Laboratories, Shionogi & Co., Ltd., 2-1-3, Kuise-Terajima, Amagasaki-shi, Hyogo, 660-0813, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Sakuma
authors.affiliation: 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.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Ida
authors.affiliation: 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.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Endoh
authors.affiliation: Laboratory of Formulation Design and Pharmaceutical Technology, Osaka University of Pharmaceutical Sciences, 4-20-1, Nasahara, Takatsuki-shi, Osaka, 569-1094, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Kadota
authors.affiliation: Laboratory of Formulation Design and Pharmaceutical Technology, Osaka University of Pharmaceutical Sciences, 4-20-1, Nasahara, Takatsuki-shi, Osaka, 569-1094, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Tozuka
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D003460:Crystallization; D004355:Drug Stability; D006358:Hot Temperature; D015999:Multivariate Analysis; D009288:Naproxen / Q000737:chemistry; D017550:Spectroscopy, Fourier Transform Infrared; D044366:Transition Temperature
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D009288:Naproxen
keywords: amorphous; co-amorphous; crystallization; glass transition temperature; intermolecular interaction; multivariate analysis