title: Characterisation of moisture uptake effects on the glass transitional behaviour of an amorphous drug using modulated temperature DSC.
abstract: The purpose of this study was to investigate the depression of the glass transition temperature, T(g), of the protease inhibitor saquinavir in the first heating scan as a function of the quantity of sorbed water by the application of modulated temperature differential scanning calorimetry (MTDSC). Samples of amorphous saquinavir were pretreated under various humidity conditions and the quantity of sorbed water measured by thermogravimetric analysis. MTDSC runs were performed using hermetically and non-hermetically sealed pans in order to determine the glass transition temperature. MTDSC allowed the separation of the glass transition from the enthalpic relaxation, thereby allowing clear visualisation of T(g) for amorphous saquinavir in the first heating scan. The plasticizing effects of water were assessed, with the depression in T(g) related to the mole fraction of water sorbed via the Gordon-Taylor relationship. An expression has been derived which allows estimation of the water content which lowers the T(g) to the storage temperature, thereby considerably increasing the risk of recrystallisation. It is argued that this model may aid prediction of the optimal storage conditions for amorphous drugs.
authors.affiliation: The School of Pharmacy, University of London, 29-39 Brunswick Square, London, UK.
authors.forename: P G
authors.initials: PG
authors.lastname: Royall
authors.forename: D Q
authors.initials: DQ
authors.lastname: Craig
authors.forename: C
authors.initials: C
authors.lastname: Doherty
mesh_terms: D000465:Algorithms; D002152:Calorimetry, Differential Scanning / Q000379:methods*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003460:Crystallization; D017320:HIV Protease Inhibitors / Q000737:chemistry; D006813:Humidity; D007536:Isomerism; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D019258:Saquinavir / Q000737:chemistry; D013818:Thermogravimetry; D014867:Water / Q000032:analysis
chemical_list: D017320:HIV Protease Inhibitors; D004364:Pharmaceutical Preparations; D014867:Water; D019258:Saquinavir