Modelling phase separation in amorphous solid dispersions

Meere, M., Pontrelli, G. and McGinty, S. (2019) Modelling phase separation in amorphous solid dispersions. Acta Biomaterialia, 94, pp. 410-424. (doi:10.1016/j.actbio.2019.06.009) (PMID:31238110)

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Abstract

Much work has been devoted to analysing thermodynamic models for solid dispersions with a view to identifying regions in the phase diagram where amorphous phase separation or drug recrystallization can occur. However, detailed partial differential equation non-equilibrium models that track the evolution of solid dispersions in time and space are lacking. Hence theoretical predictions for the timescale over which phase separation occurs in a solid dispersion are not available. In this paper, we address some of these deficiencies by (i) constructing a general multicomponent diffusion model for a dissolving solid dispersion; (ii) specializing the model to a binary drug/polymer system in storage; (iii) deriving an effective concentration dependent drug diffusion coefficient for the binary system, thereby obtaining a theoretical prediction for the timescale over which phase separation occurs; (iv) calculating the phase diagram for the Felodipine/HPMCAS system; and (iv) presenting a detailed numerical investigation of the Felodipine/HPMCAS system assuming a Flory-Huggins activity coefficient. The numerical simulations exhibit numerous interesting phenomena, such as the formation of polymer droplets and strings, Ostwald ripening/coarsening, phase inversion, and droplet-to-string transitions. A numerical simulation of the fabrication process for a solid dispersion in a hot melt extruder was also presented.

Item Type:Articles
Additional Information:The authors acknowledge funding from the European Research Council under the European Unions Horizon 2020 Framework Programme (No. FP/2014-2020)/ERC Grant Agreement No. 739964 (COPMAT).
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Pontrelli, Dr Giuseppe and Mcginty, Dr Sean and Meere, Dr Martin
Authors: Meere, M., Pontrelli, G., and McGinty, S.
College/School:College of Science and Engineering > School of Engineering
College of Science and Engineering > School of Engineering > Biomedical Engineering
Journal Name:Acta Biomaterialia
Publisher:Elsevier
ISSN:1742-7061
ISSN (Online):1878-7568
Published Online:22 June 2019
Copyright Holders:Copyright © 2019 Acta Materialia Inc.
First Published:First published in Acta Biomaterialia 94:410-424
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher

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