title: Prediction of the thermal phase diagram of amorphous solid dispersions by Flory-Huggins theory.
abstract: Miscibility of drug and polymer is one of the key parameters in amorphous formulation design. The purpose of this work is to provide a theoretical approach to evaluate miscibility between drug and polymer in amorphous solid dispersions. The model system is indomethacin and polyvinylpyrrolidone-vinyl acetate copolymer. The Flory-Huggins (F-H) interaction parameter, χ, of drug and polymer was estimated at different temperatures by two methods: melting point depression of drug in various polymer ratios at the melting temperature, and Hildebrand and Scott solubility parameter calculation at 25°C. The simplified first-order relation between the F-H interaction parameter and temperature was established. This allows the construction of a temperature-composition phase diagram of a two-component amorphous system. The spinodal curve was generated and provides an insight into the thermodynamic stability of an amorphous solid dispersion at various temperatures. The predicted stability of the model system was compared with the experimental data. The merits and deficiency of the proposed approach were fully discussed.
authors.affiliation: Department of Pharmaceutical and Analytical R&D, Hoffmann-La Roche Inc., Nutley, New Jersey 07110. Electronic address: yinyan.zhao@roche.com.
authors.forename: Yinyan
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Pharmaceutical and Analytical R&D, Hoffmann-La Roche Inc., Nutley, New Jersey 07110.
authors.forename: Petra
authors.initials: P
authors.lastname: Inbar
authors.affiliation: Department of Pharmaceutical and Analytical R&D, Hoffmann-La Roche Inc., Nutley, New Jersey 07110.
authors.forename: Hitesh P
authors.initials: HP
authors.lastname: Chokshi
authors.affiliation: Department of Pharmaceutical and Analytical R&D, Hoffmann-La Roche Inc., Nutley, New Jersey 07110.
authors.forename: A Wasseem
authors.initials: AW
authors.lastname: Malick
authors.affiliation: Department of Pharmaceutical and Analytical R&D, Hoffmann-La Roche Inc., Nutley, New Jersey 07110.
authors.forename: Duk Soon
authors.initials: DS
authors.lastname: Choi
mesh_terms: D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D003460:Crystallization; D004355:Drug Stability; D007213:Indomethacin / Q000737:chemistry*; D008956:Models, Chemical; D015394:Molecular Structure; D044367:Phase Transition; D033362:Powder Diffraction; D011759:Pyrrolidines / Q000737:chemistry*; D012995:Solubility; D013817:Thermography; D044366:Transition Temperature; D014753:Vinyl Compounds / Q000737:chemistry*; D014961:X-Ray Diffraction
chemical_list: D011759:Pyrrolidines; D014753:Vinyl Compounds; C402301:poly(vinylpyrrolidone-co-vinyl-acetate); D007213:Indomethacin