Modelling phase separation in amorphous solid dispersions
| العنوان: | Modelling phase separation in amorphous solid dispersions |
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| المؤلفون: | Martin Meere, Sean McGinty, Giuseppe Pontrelli |
| المصدر: | Acta biomaterialia 94 (2019): 410–424. doi:10.1016/j.actbio.2019.06.009 info:cnr-pdr/source/autori:Meere, Martin; Pontrelli, Giuseppe; McGinty, Sean/titolo:Modelling phase separation in amorphous solid dispersions/doi:10.1016%2Fj.actbio.2019.06.009/rivista:Acta biomaterialia/anno:2019/pagina_da:410/pagina_a:424/intervallo_pagine:410–424/volume:94 Acta Biomaterialia |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Ostwald ripening, Recrystallization (geology), Materials science, 0206 medical engineering, Biomedical Engineering, Phase separation, Thermodynamics, FOS: Physical sciences, 02 engineering and technology, Methylcellulose, Condensed Matter - Soft Condensed Matter, Biochemistry, Phase Transition, Biomaterials, Drug diffusion, symbols.namesake, Mathematical model, Amorphous solid dispersion, Diffusion (business), Molecular Biology, Dissolution, Phase diagram, Felodipine, General Medicine, 021001 nanoscience & nanotechnology, 020601 biomedical engineering, Amorphous solid, Models, Chemical, symbols, Soft Condensed Matter (cond-mat.soft), 74NXX, 74A50, 80A17, 82B26, 82C26, 0210 nano-technology, Dispersion (chemistry), Phase inversion, Biotechnology |
| الوصف: | 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. Statement of Significance Solid dispersions are products that contain mixtures of drug and other materials e.g. polymer. These are liable to separate-out over time- a phenomenon known as phase separation. This means that it is possible the product differs both compositionally and structurally between the time of manufacture and the time it is taken by the patient, leading to poor bioavailability and so ultimately the shelf-life of the product has to be reduced. Theoretical predictions for the timescale over which phase separation occurs are not currently available. Also lacking are detailed partial differential equation non-equilibrium models that track the evolution of solid dispersions in time and space. This study addresses these issues, before presenting a detailed investigation of a particular drug-polymer system. (C) 2019 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1742-7061 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0f6593f90817bbb6eb7cfdbe2e9a3b05 http://arxiv.org/abs/1902.05410 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....0f6593f90817bbb6eb7cfdbe2e9a3b05 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 17427061 |
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