title: Physical Stabilization of Pharmaceutical Glasses Based on Hydrogen Bond Reorganization under Sub-TgTemperature.
abstract: 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-Tg) on physical stability, and found that the sub-Tgannealing 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-Tgannealing originated from strengthened hydrogen bonding between molecules and probably from a better local packing associated with the stronger hydrogen bonds. The sub-Tgannealing is effective as a physical stabilization strategy for some pharmaceutical molecules, which have relatively large energy barrier for nucleation.
authors.affiliation: International Center for Materials Nanoarchitectonics, National Institute for Materials Science , 1-1 Namiki, Tsukuba, Ibaraki 305-0044, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Tominaka
authors.affiliation: International Center for Materials Nanoarchitectonics, National Institute for Materials Science , 1-1 Namiki, Tsukuba, Ibaraki 305-0044, Japan.
authors.forename: Kohsaku
authors.identifier: 0000-0002-3466-9365
authors.initials: K
authors.lastname: Kawakami
authors.affiliation: International Center for Materials Nanoarchitectonics, National Institute for Materials Science , 1-1 Namiki, Tsukuba, Ibaraki 305-0044, Japan.
authors.forename: Mayuko
authors.initials: M
authors.lastname: Fukushima
authors.affiliation: International Center for Materials Nanoarchitectonics, National Institute for Materials Science , 1-1 Namiki, Tsukuba, Ibaraki 305-0044, Japan.
authors.forename: Aoi
authors.initials: A
authors.lastname: Miyazaki
mesh_terms: D019380:Anti-HIV Agents / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning / Q000379:methods; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004355:Drug Stability; D005898:Glass / Q000737:chemistry*; D006860:Hydrogen Bonding; D019438:Ritonavir / Q000737:chemistry*; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared / Q000379:methods; D044366:Transition Temperature; D014961:X-Ray Diffraction / Q000379:methods
chemical_list: D019380:Anti-HIV Agents; D019438:Ritonavir
keywords: crystallization; pair distribution function; pharmaceutical glass; solid dispersion; stability