Quantum Chemistry and Pharmacy: Diagnostic Check of the Thermochemistry of Ibuprofen

The thermodynamic data on ibuprofen available in the literature shows that the disarray of experimental results is unacceptable for this very important drug. The data on ibuprofens available in the literature were collected, combined with our complementary experimental results and evaluated. The enthalpies of combustion and formation of the crystalline RS‐(±)‐ and S‐(+)‐ibuprofens were measured using high‐precision combustion calorimetry. The temperature dependence of the vapour pressure of S‐(+)‐ibuprofen was measured using the transpiration method and the enthalpy of vaporization was derived from this measurement. The enthalpies of fusion of both compounds were measured using DSC. The G4 calculations have been carried out to determine the enthalpy of formation in the gaseous state of the most stable conformer. Thermochemical properties of the compounds studied were evaluated and tested for consistency with the “centerpiece approach”. A set of reliable and consistent values of thermodynamic properties of ibuprofens at 298.15 K is recommended for thermochemical calculations of the pharmaceutical processes. The diagnostic protocol was developed to distinguish between the “sick” or “healthy” thermodynamic data. This diagnostic is also applicable to other drugs with a different structure than ibuprofen. The diagnostic protocol is developed to distinguish between “sick” and “healthy” thermodynamic data for active pharmaceutical ingredients. The enthalpies of combustion, vaporisation and fusion of the RS‐(±)‐ and S‐(+)‐ibuprofens are measured and combined with the G4 calculations. A set of reliable and consistent values of thermodynamic properties of ibuprofen is recommended for thermochemical calculations of the pharmaceutical processes.