A Rare Case of Mesomorphic Behavior–Molecular Reorientation of Itraconazole Liquid Crystal Induced by a Hygrothermal Treatment

Liquid crystals constitute a unique class of soft state of matter exhibiting the counterintuitive combination of fluidity and order in addition to the unique feature of controllable molecular orientation. Herein, we introduce the use of moisture sorption approach to reversibly realign mesogen molecules within a liquid crystalline phase of itraconazole, assigned to as a nematic phase (ITR-N), obtained by spray drying. This unique, nematic-to-smectic switching behavior of ITR was achieved via moisture triggered activation of molecular mobility of ITR molecules below the material’s glass transition temperature (<i>T</i><sub>g</sub>). This phenomenon was characterized using small and wide-angle X-ray diffraction, scanning electron microscopy, and thermal analysis. The smectic phase was found to be formed by a 1:1 mol/mol ITR/water complex, an example of rare thermotropic mesomorphism of a solvent complex, and the water presence was found to be necessary for the material to retain the smectic order. The ordered sample, in the smectic phase, possessed a greater <i>T</i><sub>g</sub> than ITR-N due to an increase in order and subsequent increase in rigidity. This behavior highlights the ability of ITR to accommodate stress conditions via molecular rearrangement and thus resist full crystallization, which rationalizes the importance of the liquid crystalline phase.