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Atomic force microscopy-based screening of drug-excipient miscibility and stability of solid dispersions

Lauer, M. E. and Grassmann, O. and Siam, M. and Tardio, J. and Jacob, L. and Page, S. and Kindt, J. H. and Engel, A. and Alsenz, J.. (2011) Atomic force microscopy-based screening of drug-excipient miscibility and stability of solid dispersions. Pharmaceutical research, Vol. 28, H. 3. pp. 572-584.

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Official URL: http://edoc.unibas.ch/dok/A6002472

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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.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Former Organization Units Biozentrum > Structural Biology (Engel)
UniBasel Contributors:Engel, Andreas H
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Plenum Press
ISSN:0724-8741
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:14 Sep 2012 07:22
Deposited On:14 Sep 2012 07:15

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