Formation of stoichiometric and non-stoichiometric ionic liquid and cocrystal multicomponent phases of lidocaine with azelaic acid by changing counterion ratios

Abstract

Tuning of physicochemical properties of ionic liquids and crystalline materials is a challenge that opens up unlimited possibilities for expanding applications and controlling biological activity of pharmaceutical multicomponent phases incorporating active pharmaceutical ingredients (APIs) with counterions or coformers. In this work we have investigated the effect of changing lidocaine (LID) and azelaic acid (AZE) ratios on the physicochemical properties of their corresponding multicomponent systems using a thermodynamics-based approach. Microscopy, X-ray diffraction analysis, infrared spectroscopy, nuclear magnetic resonance, and thermogravimetric analysis provided complimentary characterisation. Mechanochemical synthesis of LID:AZE systems at a range of stoichiometries yielded at least two distinct liquid phases and two distinct crystalline phases, one of which involved a unique 2:3 LID:counterion composition not observed previously. Furthermore, to the best of our knowledge the formation of oligomeric ionic liquids involving dicarboxylic acids is also being reported for the first time. This work highlights the need for a careful characterisation of multicomponent systems, especially for pharmaceutical applications.