Guiding excipient selection for physically stable amorphous solid dispersions: A combined in-vitro in-silico approach
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Author (Corporation)
Publication date
06.2025
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01A - Journal article
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Parent work
European Journal of Pharmaceutical Sciences
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Volume
212
Issue / Number
107152
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Elsevier
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Abstract
Fast screening of amorphous solid dispersions (ASDs) is a need in the pharmaceutical industry. To support this, several emerging technologies have been developed ranging from in-silico prediction to miniaturized high-throughput experimentation. However, a notable challenge lies in the absence of comparative data. In the present work, a combination of a miniaturized screening of ASDs with calculation of activity coefficients using the conductor like screening model for real solvents (COSMO-RS) was proposed. First, the physical stability of ASDs comprising drugs of different glass forming ability (GFA) each with ten pharmaceutically relevant polymers was evaluated under accelerated stress conditions at two drug:polymer ratios. The miniaturized high-throughput screening method was based on the instability onset time that was monitored by polarized light microscopy (PLM). Furthermore, COSMO-RS was used to assess the interaction strength between the drugs and polymers by calculating activity coefficients, which was combined with estimations of the wet glass transition temperature (Tg), to account for molecular mobility. The computational calculations showed an overall alignment of 87 % with the instability of the ASDs observed experimentally for comparable drug:polymer ratios and humidity conditions. This positive result supports the current understanding of stable ASD formulation where at given ambient conditions, a low molecular mobility as well as the strength of interaction between drug and polymer has a main impact on the physical stability of ASDs. The current results are further encouraging to implement such a combined in-vitro/high-throughput (HTS) and in-silico strategy in early industrial screening of ASDs.
Keywords
Amorphous solid dispersion, COSMO-RS, High-throughput screening, Physical stability
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ISBN
ISSN
0928-0987
1879-0720
1879-0720
Language
English
Created during FHNW affiliation
Yes
Strategic action fields FHNW
Publication status
Published
Review
Peer review of the complete publication
Open access category
Gold
License
Citation
Zeneli, E., Bohets, H., Mebenga, F. N., Holm, R., Tistaert, C., & Kuentz, M. (2025). Guiding excipient selection for physically stable amorphous solid dispersions: A combined in-vitro in-silico approach. European Journal of Pharmaceutical Sciences, 212(107152). https://doi.org/10.1016/j.ejps.2025.107152