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Molecules 2017, 22(2), 296;

Amorphous-Amorphous Phase Separation in API/Polymer Formulations

TU Dortmund, Department of Biochemical and Chemical Engineering, Laboratory of Thermodynamics, Emil-Figge-Str. 70, D-44227 Dortmund, Germany
Author to whom correspondence should be addressed.
Academic Editors: Guy Van den Mooter and Holger Grohganz
Received: 22 December 2016 / Revised: 8 February 2017 / Accepted: 9 February 2017 / Published: 15 February 2017
(This article belongs to the Collection Poorly Soluble Drugs)
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The long-term stability of pharmaceutical formulations of poorly-soluble drugs in polymers determines their bioavailability and therapeutic applicability. However, these formulations do not only often tend to crystallize during storage, but also tend to undergo unwanted amorphous-amorphous phase separations (APS). Whereas the crystallization behavior of APIs in polymers has been measured and modeled during the last years, the APS phenomenon is still poorly understood. In this study, the crystallization behavior, APS, and glass-transition temperatures formulations of ibuprofen and felodipine in polymeric PLGA excipients exhibiting different ratios of lactic acid and glycolic acid monomers in the PLGA chain were investigated by means of hot-stage microscopy and DSC. APS and recrystallization was observed in ibuprofen/PLGA formulations, while only recrystallization occurred in felodipine/PLGA formulations. Based on a successful modeling of the crystallization behavior using the Perturbed-Chain Statistical Associating Fluid Theory (PC-SAFT), the occurrence of APS was predicted in agreement with experimental findings. View Full-Text
Keywords: poorly water-soluble drug; amorphous solid dispersion; PLGA; thermodynamic model; phase behavior; amorphous-amorphous phase separation poorly water-soluble drug; amorphous solid dispersion; PLGA; thermodynamic model; phase behavior; amorphous-amorphous phase separation

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Luebbert, C.; Huxoll, F.; Sadowski, G. Amorphous-Amorphous Phase Separation in API/Polymer Formulations. Molecules 2017, 22, 296.

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