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Atomic Force Microscopy-Based Screening of Drug-Excipient Miscibility and Stability of Solid Dispersions

Lauer, Matthias ; Grassmann, Olaf ; Siam, Monira ; Tardio, Joseph ; Jacob, Laurence ; Page, Susanne ; Kindt, Johannes ; Engel, Andreas ; Alsenz, Jochem

In: Pharmaceutical Research, 2011, vol. 28, no. 3, p. 572-584

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    Titre
    • Atomic Force Microscopy-Based Screening of Drug-Excipient Miscibility and Stability of Solid Dispersions
    Auteur
    • Lauer, Matthias. Center for Cellular Imaging and Nanoanalytics, Biozentrum, University of Basel, Mattenstrasse 26, CH 4006, Basel, Switzerland
    • Grassmann, Olaf. F. Hoffmann-La Roche Ltd., Discovery Technologies, CH-4070, Basel, Switzerland
    • Siam, Monira. F. Hoffmann-La Roche Ltd., Discovery Technologies, CH-4070, Basel, Switzerland
    • Tardio, Joseph. F. Hoffmann-La Roche Ltd., Formulation Research, CH-4070, Basel, Switzerland
    • Jacob, Laurence. F. Hoffmann-La Roche Ltd., Formulation Research, CH-4070, Basel, Switzerland
    • Page, Susanne. F. Hoffmann-La Roche Ltd., Formulation Research, CH-4070, Basel, Switzerland
    • Kindt, Johannes. Bruker Nano GmbH, Dynamostrasse 19, 68165, Mannheim, Germany
    • Engel, Andreas. Center for Cellular Imaging and Nanoanalytics, Biozentrum, University of Basel, Mattenstrasse 26, CH 4006, Basel, Switzerland
    • Alsenz, Jochem. F. Hoffmann-La Roche Ltd., Formulation Research, CH-4070, Basel, Switzerland
    Type de document
    • Postprint
    Langue
    • Inglese
    Publié dans
    • Pharmaceutical Research, 2011, vol. 28, no. 3, p. 572-584. Springer US; http://www.springer-ny.com
    Autre version électronique
    Identifiant OAI-PMH
    • oai:doc.rero.ch:318753
    Summary
    ABSTRACT: Purpose: Development of a method to assess the drug/polymer miscibility and stability of solid dispersions using a melt-based mixing method. Methods: Amorphous fractured films are prepared and characterized with Raman Microscopy in combination with Atomic Force Microscopy to discriminate between homogenously and heterogeneously mixed drug/polymer combinations. The homogenous combinations are analyzed further for physical stability under stress conditions, such as increased humidity or temperature. Results: Combinations that have the potential to form a molecular disperse mixture are identified. Their potential to phase separate is determined through imaging at molecular length scales, which results in short observation time. De-mixing is quantified by phase separation analysis, and the drug/polymer combinations are ranked to identify the most stable combinations. Conclusions: The presented results demonstrate that drug/polymer miscibility and stability of solid dispersions, with many mechanistic details, can be analyzed with Atomic Force Microscopy. The assay allows to identify well-miscible and stable combinations within hours or a few days