Crystal Structure and Behavior of the Cocrystal Salt (±)Ibuprofen2HK

Salt formation is a key strategy to optimize the physicochemical properties of active pharmaceutical ingredients. The synthesis and characterization of a 2:1 cocrystal salt of racemic ibuprofen with potassium, (±)Ibu2HK, are reported, and the salt is identified as a Speakman salt. Single-crystal X-ray diffraction reveals an asymmetric unit containing three independent ibuprofen molecules and 1 + 0.5 potassium cations occupying two distinct coordination environments, with two short carboxyl–carboxylate O⋯O contacts (2.437 and 2.447 Å), each bridged by a shared hydrogen atom. The behaviors of the cocrystal salt (±)Ibu2HK and the salt (±)IbuK are also compared. (±)Ibu2HK shows negligible moisture uptake (<0.5%) across the 0–90% RH range, in contrast to the deliquescent behavior of (±)IbuK. Upon heating, (±)Ibu2HK melts at 121 °C and dissociates into recrystallized (±)IbuK and evaporated (±)IbuH, with a mass loss of 48.4 wt% measured by TGA-DSC, consistent with the theoretical value of 45.8 wt%. In water, (±)Ibu2HK fully dissociates as well, firstly releasing the ionic species (±)Ibu− and K+ into solution while (±)IbuH precipitates. Thus, the pH of the resulting suspension is always higher than the pKa of the acid.