Variation of the experimental conditions allowed expansion of the crystal form landscape of the binary system of a promising neuroprotective, antidepressant, and antineoplastic drug riluzole with 2,4-dihydroxybenzoic acid. Four new solid forms were identified, including a low-temperature polymorphic modification of a (1:1) salt, a (2:1) salt cocrystal, and two solvates with tetrahydrofuran and 1,4-dioxane. In addition, the (1:1) cocrystal of riluzole and 4-dihydroxybenzoic acid was obtained and characterized. A robust hydrogen-bonding motif common for the riluzole multicomponent crystals was discovered and rationalized based on the molecular electrostatic potential maps for the isolated heterodimers and quantitative analysis of noncovalent interactions. The colossal scissor-like combined positive/negative anisotropic thermal expansion of the (1:1) salt, which was observed for the first time for a pharmaceutical solid, led to a substantial change in the powder diffraction pattern that could be easily misattributed to the novel polymorphic form. The pH-solubility behavior of the multicomponent crystals with different ionization state and stoichiometric ratio of the components was investigated in order to select the potential candidates with optimal in vivo dissolution parameters in different biological media. The effect of various predissolved excipients on the nucleation and precipitation of the riluzole base during its release from the multicomponent crystals was studied in the blank FaSSIF medium.
