Experimental Investigation and Modeling of Cocrystal Formation in L-Menthol/Thymol Eutectic System

Solid-liquid equilibria (SLE) of the (L)-menthol/thymol eutectic system were studied in detail using a combination of differential scanning calorimetry (DSC) and powder X-ray diffraction (XRD). The existence of two cocrystals with stoichiometric ratios 1:3 and 3:2 for (L)-menthol:thymol was monitored by performing XRD on samples of different compositions. Moreover, the existence of two solid solution regions of l-menthol in thymol and (L)-menthol in the 1:3 cocrystal was observed. The nonrandom two-liquid (NRTL) and two-suffix Margules models were applied to model the measured SLE data. The two eutectic points of the system were determined at T-e1(cal) = 271.7 K, x(thymol,e1)(cal) = 0.48 and T-e2(cal) = 273.1 K, x(thymol,e2)(cal) = 0.33. The complex character of the obtained phase diagram of the system shows that not all deep eutectic systems can be assumed to be of a simple eutectic type with immiscible solid phases. For the accurate determination of the SLE of eutectic systems, a combination of several experimental techniques and thermodynamic modeling is needed.