title: Amorphous-Amorphous Phase Separation in API/Polymer Formulations.
abstract: 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.
authors.affiliation: TU Dortmund, Department of Biochemical and Chemical Engineering, Laboratory of Thermodynamics, Emil-Figge-Str. 70, D-44227 Dortmund, Germany. christian.luebbert@bci.tu-dortmund.de.
authors.forename: Christian
authors.initials: C
authors.lastname: Luebbert
authors.affiliation: TU Dortmund, Department of Biochemical and Chemical Engineering, Laboratory of Thermodynamics, Emil-Figge-Str. 70, D-44227 Dortmund, Germany. fabian.huxoll@bci.tu-dortmund.de.
authors.forename: Fabian
authors.initials: F
authors.lastname: Huxoll
authors.affiliation: TU Dortmund, Department of Biochemical and Chemical Engineering, Laboratory of Thermodynamics, Emil-Figge-Str. 70, D-44227 Dortmund, Germany. gabriele.sadowski@bci.tu-dortmund.de.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Sadowski
mesh_terms: D000465:Algorithms; D002152:Calorimetry, Differential Scanning; D005591:Chemical Fractionation; D004339:Drug Compounding; D008956:Models, Chemical; D015394:Molecular Structure; D004364:Pharmaceutical Preparations / Q000737:chemistry* / Q000302:isolation & purification*; D011108:Polymers; D012995:Solubility; D013816:Thermodynamics; D044366:Transition Temperature
chemical_list: D004364:Pharmaceutical Preparations; D011108:Polymers
keywords: PLGA; amorphous solid dispersion; amorphous-amorphous phase separation; phase behavior; poorly water-soluble drug; thermodynamic model