Pregabalin Cocrystals with Carboxylic Acid: Structural and Thermal Analyses

Abstract

Cocrystals of pregabalin (PGB) with different carboxylic acids were developed, and their crystal structures were determined by single crystal X-ray diffraction. All obtained cocrystal structures were isostructural and related to the free PGB crystal structure (PGB_AN). These structural similarities result in analogous thermal behavior: upon heating, cocrystals segregate, with PGB_AN as one of the final products. Notably, cocrystals formed with octanoic acid exhibited multiple single crystal to single crystal phase transitions upon heating. Initially, the 1:1 stoichiometric sample exhibited a disproportion transition at 44 °C. As a result, the single crystal is a new cocrystal of 1:2 stoichiometry. Further heating induced segregation, ultimately yielding a PGB_AN single crystal. Similar behavior was observed in cocrystals with decanoic acid, but a different structure is observed in the 1:2 stoichiometry cocrystal.