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Analytical and Computational Methods for the Estimation of Drug-Polymer Solubility and Miscibility in Solid Dispersions Development

1
Department of Pharmaceutical Technology and Cosmetology, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, 11221 Belgrade, Serbia
2
Department of Pharmaceutical Technology, Faculty of Pharmacy, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece
*
Author to whom correspondence should be addressed.
Pharmaceutics 2019, 11(8), 372; https://doi.org/10.3390/pharmaceutics11080372
Received: 28 June 2019 / Revised: 18 July 2019 / Accepted: 22 July 2019 / Published: 1 August 2019
(This article belongs to the Special Issue Recent Progress in Solid Dispersion Technology)
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Abstract

The development of stable solid dispersion formulations that maintain desired improvement of drug dissolution rate during the entire shelf life requires the analysis of drug-polymer solubility and miscibility. Only if the drug concentration is below the solubility limit in the polymer, the physical stability of solid dispersions is guaranteed without risk for drug (re)crystallization. If the drug concentration is above the solubility, but below the miscibility limit, the system is stabilized through intimate drug-polymer mixing, with additional kinetic stabilization if stored sufficiently below the mixture glass transition temperature. Therefore, it is of particular importance to assess the drug-polymer solubility and miscibility, to select suitable formulation (a type of polymer and drug loading), manufacturing process, and storage conditions, with the aim to ensure physical stability during the product shelf life. Drug-polymer solubility and miscibility can be assessed using analytical methods, which can detect whether the system is single-phase or not. Thermodynamic modeling enables a mechanistic understanding of drug-polymer solubility and miscibility and identification of formulation compositions with the expected formation of the stable single-phase system. Advance molecular modeling and simulation techniques enable getting insight into interactions between the drug and polymer at the molecular level, which determine whether the single-phase system formation will occur or not. View Full-Text
Keywords: solid dispersions; miscibility; solubility; thermodynamic modeling; phase diagram; molecular dynamics simulation; thermal analysis; spectroscopic techniques solid dispersions; miscibility; solubility; thermodynamic modeling; phase diagram; molecular dynamics simulation; thermal analysis; spectroscopic techniques
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Medarević, D.; Djuriš, J.; Barmpalexis, P.; Kachrimanis, K.; Ibrić, S. Analytical and Computational Methods for the Estimation of Drug-Polymer Solubility and Miscibility in Solid Dispersions Development. Pharmaceutics 2019, 11, 372.

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