title: Investigation of phase diagrams and physical stability of drug-polymer solid dispersions.
abstract: Solid dispersion technology has been widely explored to improve the solubility and bioavailability of poorly water-soluble compounds. One of the critical drawbacks associated with this technology is the lack of physical stability, i.e. the solid dispersion would undergo recrystallization or phase separation thus limiting a product's shelf life. In the current study, the melting point depression method was utilized to construct a complete phase diagram for felodipine (FEL)-Soluplus® (SOL) and ketoconazole (KTZ)-Soluplus® (SOL) binary systems, respectively, based on the Flory-Huggins theory. The miscibility or solubility of the two compounds in SOL was also determined. The Flory-Huggins interaction parameter χ values of both systems were calculated as positive at room temperature (25 °C), indicating either compound was miscible with SOL. In addition, the glass transition temperatures of both solid dispersion systems were theoretically predicted using three empirical equations and compared with the practical values. Furthermore, the FEL-SOL solid dispersions were subjected to accelerated stability studies for up to 3 months.
authors.affiliation: Department of Pharmaceutics & Drug Delivery, School of Pharmacy, The University of Mississippi , University, MS , USA .
authors.forename: Jiannan
authors.initials: J
authors.lastname: Lu
authors.forename: Sejal
authors.initials: S
authors.lastname: Shah
authors.forename: Seongbong
authors.initials: S
authors.lastname: Jo
authors.forename: Soumyajit
authors.initials: S
authors.lastname: Majumdar
authors.forename: Andreas
authors.initials: A
authors.lastname: Gryczke
authors.forename: Karl
authors.initials: K
authors.lastname: Kolter
authors.forename: Nigel
authors.initials: N
authors.lastname: Langley
authors.forename: Michael A
authors.initials: MA
authors.lastname: Repka
mesh_terms: D002152:Calorimetry, Differential Scanning; D004355:Drug Stability; D015736:Felodipine / Q000032:analysis; D006860:Hydrogen Bonding; D007654:Ketoconazole / Q000032:analysis; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D011092:Polyethylene Glycols; D011108:Polymers / Q000737:chemistry*; D011145:Polyvinyls; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D013816:Thermodynamics; D013818:Thermogravimetry; D014961:X-Ray Diffraction
chemical_list: D004364:Pharmaceutical Preparations; D011108:Polymers; D011145:Polyvinyls; C572167:polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer; D011092:Polyethylene Glycols; D015736:Felodipine; D007654:Ketoconazole
keywords: Felodipine; Flory–Huggins theory; Soluplus®; ketoconazole; miscibility/solubility; phase diagram; physical stability; solid dispersions