title: The Application of Modeling and Prediction to the Formation and Stability of Amorphous Solid Dispersions.
abstract: Amorphous solid dispersion (ASD) formulation development is frequently difficult owing to the inherent physical instability of the amorphous form, and limited understanding of the physical and chemical interactions that translate to initial dispersion formation and long-term physical stability. Formulation development for ASDs has been historically accomplished through trial and error or experience with extant systems; however, rational selection of appropriate excipients is preferred to reduce time to market and decrease costs associated with development. Current efforts to develop thermodynamic and computational models attempt to rationally direct formulation and show promise. This review compiles and evaluates important methods used to predict ASD formation and physical stability. Recent literature in which these methods are applied is also reviewed, and limitations of each method are discussed.
authors.affiliation: Department of Pharmaceutical Sciences, Duquesne University, 600 Forbes Av, Pittsburgh, Pennsylvania 15282.
authors.forename: Kevin
authors.initials: K
authors.lastname: DeBoyace
authors.affiliation: Department of Pharmaceutical Sciences, Duquesne University, 600 Forbes Av, Pittsburgh, Pennsylvania 15282. Electronic address: wildfongp@duq.edu.
authors.forename: Peter L D
authors.initials: PLD
authors.lastname: Wildfong
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods; D004337:Drug Carriers / Q000737:chemistry; D004355:Drug Stability; D005079:Excipients / Q000737:chemistry; D006801:Humans; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry; D012995:Solubility / Q000187:drug effects; D013816:Thermodynamics
chemical_list: D004337:Drug Carriers; D005079:Excipients; D004364:Pharmaceutical Preparations; D011108:Polymers
keywords: QSPR; amorphous; in silico modeling; kinetics; molecular dynamics; molecular modeling; physical stability; solid dispersion; solid solutions; thermodynamics