title: Classification of the crystallization behavior of amorphous active pharmaceutical ingredients in aqueous environments.
abstract: OBJECTIVE
  To classify the crystallization behavior of amorphous active pharmaceutical ingredients (API) exposed to aqueous environments.
  
  
  METHODS
  A set of approximately 50 chemically and physically diverse active pharmaceutical ingredients (APIs) was selected for this study. Two experimental setups were employed to characterize the crystallization behavior of the amorphous API in an aqueous environment. For the first approach, precipitation, as evidenced by the development of turbidity, was induced using the solvent shift method, by mixing concentrated API solutions in DMSO with an aqueous buffer in a capillary. Subsequently, crystallization was monitored in situ over time using synchrotron radiation (simultaneous SAXS/WAXS beamline 12-ID-B at the Advanced Photon Source, Argonne National Laboratories, Argonne, IL). In the second approach, amorphous films were prepared by melt quenching; after adding buffer, crystallization was monitored with time using polarized light microscopy.
  
  
  RESULTS
  In general, the crystallization behavior of a given compound was similar irrespective of the experimental method employed. However, the crystallization behavior among different compounds varied significantly, ranging from immediate and complete crystallization to no observable crystallization over biorelevant time scales. Comparison of the observed behavior with previous studies of crystallization tendency in non-aqueous environments revealed that the crystallization tendency of individual APIs was somewhat similar regardless of the crystallization environment.
  
  
  CONCLUSIONS
  API properties, rather than the method by which amorphous materials are generated, tend to dictate crystallization behavior in aqueous media.
authors.affiliation: Department of Industrial and Physical Pharmacy, College of Pharmacy, Purdue University, 575 Stadium Mall Drive, West Lafayette, Indiana, 47907, USA.
authors.forename: Bernard
authors.initials: B
authors.lastname: Van Eerdenbrugh
authors.forename: Shweta
authors.initials: S
authors.lastname: Raina
authors.forename: Yi-Ling
authors.initials: YL
authors.lastname: Hsieh
authors.forename: Patrick
authors.initials: P
authors.lastname: Augustijns
authors.forename: Lynne S
authors.initials: LS
authors.lastname: Taylor
mesh_terms: D003460:Crystallization; D004364:Pharmaceutical Preparations / Q000737:chemistry* / Q000145:classification*; D019999:Pharmaceutical Solutions / Q000737:chemistry / Q000145:classification; D014867:Water / Q000737:chemistry*; D014961:X-Ray Diffraction / Q000379:methods
chemical_list: D004364:Pharmaceutical Preparations; D019999:Pharmaceutical Solutions; D014867:Water