title: Influence of copolymer composition on the phase behavior of solid dispersions.
abstract: The incorporation of poorly soluble active pharmaceutical ingredients (APIs) into excipients (e.g., polymers) to formulate an amorphous solid dispersion is a promising strategy to improve the oral bioavailability of the API. The application of copolymer excipients allows access to combinations of different monomers and thus to the design of excipients to improve solid-dispersion properties. In this work, the thermodynamic phase behavior of solid dispersions was investigated as a function of the API, type of monomer, and copolymer composition. The glass-transition temperatures and API solubilities in the solid dispersions of naproxen and indomethacin in polyvinylpyrrolidone, polyvinyl acetate, and copolymers with different weight fractions of vinylpyrrolidone and vinyl actetate were investigated. It is shown that the thermodynamic phase behavior of API/copolymer solid dispersions is a function of monomer type and copolymer composition. This effect was also predicted by using the perturbed-chain statistical associating fluid theory (PC-SAFT). The glass-transition temperature of the solid dispersions was calculated with the Gordon-Taylor equation.
authors.affiliation: Department of Biochemical and Chemical Engineering, Laboratory of Thermodynamics, TU Dortmund , Emil-Figge-Str. 70, D-44227 Dortmund, Germany.
authors.forename: Anke
authors.initials: A
authors.lastname: Prudic
authors.forename: Tobias
authors.initials: T
authors.lastname: Kleetz
authors.forename: Marcel
authors.initials: M
authors.lastname: Korf
authors.forename: Yuanhui
authors.initials: Y
authors.lastname: Ji
authors.forename: Gabriele
authors.initials: G
authors.lastname: Sadowski
mesh_terms: D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D004355:Drug Stability; D005079:Excipients / Q000737:chemistry*; D005898:Glass / Q000737:chemistry*; D007213:Indomethacin / Q000737:chemistry*; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D044367:Phase Transition; D011108:Polymers / Q000737:chemistry*; D011205:Povidone / Q000737:chemistry*; D012995:Solubility; D013816:Thermodynamics; D044366:Transition Temperature
chemical_list: D005079:Excipients; D004364:Pharmaceutical Preparations; D011108:Polymers; D011205:Povidone; D007213:Indomethacin
keywords: PC-SAFT; copolymer; indomethacin; naproxen; phase behavior; poorly soluble pharmaceutical; thermodynamic model