Amorphous-Amorphous Phase Separation in API/Polymer Formulations

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.