title: Influence of humidity on the phase behavior of API/polymer formulations.
abstract: Amorphous formulations of APIs in polymers tend to absorb water from the atmosphere. This absorption of water can induce API recrystallization, leading to reduced long-term stability during storage. In this work, the phase behavior of different formulations was investigated as a function of relative humidity. Indomethacin and naproxen were chosen as model APIs and poly(vinyl pyrrolidone) (PVP) and poly(vinyl pyrrolidone-co-vinyl acetate) (PVPVA64) as excipients. The formulations were prepared by spray drying. The water sorption in pure polymers and in formulations was measured at 25°C and at different values of relative humidity (RH=25%, 50% and 75%). Most water was absorbed in PVP-containing systems, and water sorption was decreasing with increasing API content. These trends could also be predicted in good agreement with the experimental data using the thermodynamic model PC-SAFT. Furthermore, the effect of absorbed water on API solubility in the polymer and on the glass-transition temperature of the formulations was predicted with PC-SAFT and the Gordon-Taylor equation, respectively. The absorbed water was found to significantly decrease the API solubility in the polymer as well as the glass-transition temperature of the formulation. Based on a quantitative modeling of the API/polymer phase diagrams as a function of relative humidity, appropriate API/polymer compositions can now be selected to ensure long-term stable amorphous formulations at given storage conditions.
authors.affiliation: TU Dortmund, Department of Biochemical and Chemical Engineering, Laboratory of Thermodynamics, Emil-Figge-Str. 70, D-44227 Dortmund, Germany.
authors.forename: Anke
authors.initials: A
authors.lastname: Prudic
authors.affiliation: TU Dortmund, Department of Biochemical and Chemical Engineering, Laboratory of Thermodynamics, Emil-Figge-Str. 70, D-44227 Dortmund, Germany.
authors.forename: Yuanhui
authors.initials: Y
authors.lastname: Ji
authors.affiliation: TU Dortmund, Department of Biochemical and Chemical Engineering, Laboratory of Thermodynamics, Emil-Figge-Str. 70, D-44227 Dortmund, Germany.
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. Electronic address: Gabriele.Sadowski@bci.tu-dortmund.de.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Sadowski
mesh_terms: D065966:Absorption, Physicochemical; D002626:Chemistry, Pharmaceutical; D006813:Humidity; D007213:Indomethacin / Q000737:chemistry*; D008956:Models, Chemical; D015394:Molecular Structure; D009288:Naproxen / Q000737:chemistry*; D044367:Phase Transition; D011205:Povidone / Q000737:chemistry*; D011759:Pyrrolidines / Q000737:chemistry*; D014753:Vinyl Compounds / Q000737:chemistry*; D014867:Water / Q000737:chemistry
chemical_list: D011759:Pyrrolidines; D014753:Vinyl Compounds; C402301:poly(vinylpyrrolidone-co-vinyl-acetate); D014867:Water; D009288:Naproxen; D011205:Povidone; D007213:Indomethacin
keywords: Indomethacin; Naproxen; PC-SAFT; Phase behavior; Poorly-soluble pharmaceutical; Relative humidity; Thermodynamic model; Water sorption