Thermodynamic and kinetic analysis of the melting process of S-ketoprofen and lidocaine mixtures†

Eutectic mixtures are often used in drug design and delivery. Herein, thermodynamic and kinetic analyses of the melting process of S-ketoprofen (KTP)/lidocaine (LDC) mixtures were performed by using differential scanning calorimetry (DSC) and Fourier-transform infrared spectroscopy (FTIR) measurements to trace the composition and melting process of KTP/LDC mixtures. In the binary solid–liquid phase diagram, a constant melting point of 294 K was observed, which is lower than the theoretical eutectic point of 304 K. It is believed that the hydrogen-bonding interactions between KTP and LDC caused a further decrease in the melting point. Melting at 304 K resulted from a eutectic reaction, whereas melting at 294 K was interpreted as the preliminary melting step. A kinetic analysis of the melting process was made possible by performing singular value decomposition (SVD) on a dataset of the FTIR spectra. The principal component vector indicating the magnitude of the contribution of the preliminary melting step reflects the time change in which the molten KTP signal increases after the molten LDC signal increases, which fits the sequential reaction equation. This confirms the preliminary melting stage at 294 K, as indicated by the binary solid–liquid phase diagram obtained by DSC. The activation energy was determined from the reaction rate constant, and a scenario for forming a eutectic mixture was proposed based on the mole fractions of KTP and LDC.