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Updated: Jun 7, 2026

A Package of Established Analytical Tools to Investigate the Solid-State Alteration of Lipid-Based Excipients
Published on: August 9, 2022
Atomic force microscopy-based screening of drug-excipient miscibility and stability of solid dispersions
Matthias Eckhard Lauer1, Olaf Grassmann, Monira Siam
1Center for Cellular Imaging and Nanoanalytics, Biozentrum, University of Basel, Mattenstrasse 26, CH 4006 Basel, Switzerland. Matthias.Lauer@roche.com
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.
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