Pharm Res DOI 10.1007/s11095-013-1216-z
RESEARCH PAPER
Classification of the Crystallization Behavior of Amorphous Active Pharmaceutical Ingredients in Aqueous Environments Bernard Van Eerdenbrugh & Shweta Raina & Yi-Ling Hsieh & Patrick Augustijns & Lynne S. Taylor Received: 20 May 2013 / Accepted: 18 September 2013 # Springer Science+Business Media New York 2013
ABSTRACT Purpose 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. B. Van Eerdenbrugh : S. Raina : Y.
RESEARCH PAPER
Classification of the Crystallization Behavior of Amorphous Active Pharmaceutical Ingredients in Aqueous Environments Bernard Van Eerdenbrugh & Shweta Raina & Yi-Ling Hsieh & Patrick Augustijns & Lynne S. Taylor Received: 20 May 2013 / Accepted: 18 September 2013 # Springer Science+Business Media New York 2013
ABSTRACT Purpose 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. B. Van Eerdenbrugh : S. Raina : Y.
