Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8513544 | Journal of Pharmaceutical Sciences | 2018 | 67 Pages |
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.
Keywords
DSCGFAAPIMLRPVPVAPVPPLSDFTPCAAmorphousEnthalpy of mixingQSPRPrincipal component analysisThermodynamicsGlass-forming abilityPhysical stabilityMolar volumePartial least squaresIn silico modelingForce fieldglass transition temperatureMelting TemperatureMolecular dynamicsSolid solutionsMultiple linear regressionGroup contributionKineticsSupport vector machinesSVMMolecular modelingActive Pharmaceutical IngredientDensity functional theoryASDMolecular weightFlory-Huggins interaction parameterSolid dispersionAmorphous solid dispersionpolyethylene glycolpolyvinylpyrrolidonePEGDifferential scanning calorimetry
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Authors
Kevin DeBoyace, Peter L.D. Wildfong,