Theoretical Aspects of Differential Scanning Calorimetry as a Tool for the Studies of Equilibrium Thermodynamics in Pharmaceutical Solid Phase Transitions.
Although differential scanning calorimetry (DSC) is a non-equilibrium technique, it has been used to gain energetic information that involves phase equilibria. DSC has been widely used to characterize the equilibrium melting parameters of small organic pharmaceutical compounds. An understanding of how DSC measures an equilibrium event could make for a better interpretation of the results. The aim of this mini-review was to provide a theoretical insight into the DSC measurement to obtain the equilibrium thermodynamics of a phase transition especially the melting process. It was demonstrated that the heat quantity obtained from the DSC thermogram (ΔH) was related to the thermodynamic enthalpy of the phase transition (ΔH (P) ) via: ΔH = ΔH (P) /(1 + K (- 1)) where K was the equilibrium constant. In melting, the solid and liquefied phases presumably coexist resulting in a null Gibbs free energy that produces an infinitely larger K. Thus, ΔH could be interpreted as ΔH (P). Issues of DSC investigations on melting behavior of crystalline solids including polymorphism, degradation impurity due to heating in situ, and eutectic melting were discussed. In addition, DSC has been a tool for determination of the impurity based on an ideal solution of the melt that is one of the official methods used to establish the reference standard.
Drug Delivery System Excellent Center, Department of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat Yai, 90112, Thailand. damrongsak.f@psu.ac.th.
Damrongsak
D
Faroongsarng
D002152:Calorimetry, Differential Scanning / Q000379:methods; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D019999:Pharmaceutical Solutions / Q000032:analysis* / Q000737:chemistry; D044367:Phase Transition; D013816:Thermodynamics
D019999:Pharmaceutical Solutions
differential scanning calorimetry; enthalpy of fusion; equilibrium thermodynamics; melting transition