The long-term stability of pharmaceutical formulations of poorly-soluble drugs in\npolymers determines their bioavailability and therapeutic applicability. However, these formulations\ndo not only often tend to crystallize during storage, but also tend to undergo unwanted\namorphous-amorphous phase separations (APS). Whereas the crystallization behavior of APIs in\npolymers has been measured and modeled during the last years, the APS phenomenon is still\npoorly understood. In this study, the crystallization behavior, APS, and glass-transition temperatures\nformulations of ibuprofen and felodipine in polymeric PLGA excipients exhibiting different ratios of\nlactic acid and glycolic acid monomers in the PLGA chain were investigated by means of hot-stage\nmicroscopy and DSC. APS and recrystallization was observed in ibuprofen/PLGA formulations,\nwhile only recrystallization occurred in felodipine/PLGA formulations. Based on a successful\nmodeling of the crystallization behavior using the Perturbed-Chain Statistical Associating Fluid\nTheory (PC-SAFT), the occurrence of APS was predicted in agreement with experimental findings.
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