Revised phase diagrams based on racemic ibuprofen with thymol and l-menthol

Abstract

The phase diagrams between thymol and racemic ibuprofen, on the one hand, and between l-menthol and this same ibuprofen, on the other hand, were reviewed and corrected using thermal analysis and thermodynamic approach. The Tammann diagrams constructed from thermal analysis data coupled with the thermodynamic assessments allowed to conclude that the two systems present a eutectic behavior with complete immiscibility in the solid state between the components. For l-menthol–ibuprofen system, this is in contradiction with what it was previously mentioned. Indeed, no eutectic reaction was observed on the l-menthol rich side. This result was previously observed for samples melted before being cooled. Indeed, it happens that one of the two components does not recrystallize once cooled down, preventing at this time from observing the eutectic reaction. In the present case, racemic ibuprofen does not regularly recrystallize once melted, as previously reported for other systems involving this component. In the present study, the samples were prepared and homogenized in a solid state without passing through a pre-melting. Owing to thermodynamic assessment and Gibbs energy calculations, one can conclude that repulsive interactions or attractive interactions take place in the liquid state depending on the system. A packing coefficient is introduced to assess the similarity of the molecules, allowing to discuss the possible formation of solid solution within both systems.