Beware with the Quality of Thermodynamic Data Diagnostic Check of Phase Transitions Energetics of Active Pharmaceutical Ingredients

Abstract

Thermodynamics is crucial for optimizing drug synthesis, developing pharmaceutical formulations and ensuring their stability, effectiveness and safety. The thermochemical properties of active pharmaceutical ingredients with the common biphenyl motif (RS-Flurbiprofen, Diflunisal, Fenbufen and Biprofen) available in the literature were collected, combined with our own complementary experimental results and evaluated. The vapour pressures temperature dependence of RS-Flurbiprofen was measured using the Knudsen effusion method, and the enthalpy of sublimation was obtained from this measurement. The enthalpy of fusion of RS-Flurbiprofen was measured using DSC. A reliable diagnostic method has been outlined to evaluate the quality of the available experimental thermodynamic data of drugs. The data previously available in the literature for RS-flurbiprofen, diflunisal and fenbufen were analysed and diagnosed as "thick". For RS-flurbiprofen, diflunisal, fenbufen and biprofen, the consistent sets of thermodynamic data were evaluated and recommended for the calculations of the pharmaceutic processes. The "paper-and-pencil" concept presented in this paper can be extended to the diagnosis of "sick" or "healthy" experimental thermodynamic data for pharmaceuticals with a structure other than profens.