Lidocaine/l-Menthol Binary System: Cocrystallization versus Solid-State Immiscibility

We present the synthesis, structure determination, and thermodynamic
properties of a never reported cocrystal prepared with lidocaine and l-menthol. The temperature−composition phase diagram
of the lidocaine/l-menthol binary system was achieved using
differential scanning calorimetry and X-ray diffraction experiments.
The present study demonstrates that the only way to perform a phase
equilibrium survey of the lidocaine/l-menthol system is to
prepare the binary mixtures from the cocrystal, an equimolar stoichiometric
compound of l-menthol and lidocaine. We describe a process
that is crucial to elaborate pharmaceutical agents that remain in
their thermodynamical stable state throughout their preparation, manufacture,
and storage for effective use.