Cocrystals of Leflunomide: Design, Structural, and Physicochemical Evaluation

The use of cocrystallization as a tool to improve the pharmaceutical profile of the low-solubility drug leflunomide, used in the treatment of arthritis, is herein evaluated. Judicious selection of coformers based upon knowledge-based strategy and crystal engineering principles has resulted in new cocrystals with pyrogallol, 3-hydroxybenzoic acid, 2-picolinic acid, and 2-aminopyrimidine. Characterization and structure determination of these systems were performed using X-ray diffraction. Crystal structure analysis revealed that the hydrogen bonding in the crystal structures corroborates well with the knowledge-based prediction tool. Physicochemical properties such as thermal behavior, stability, solubility, and dissolution rate of the pharmaceutically acceptable cocrystals were evaluated to assess their impact on the pharmaceutical profile of leflunomide. When compared with their parent compound leflunomide and the physical mixtures, cocrystals were found to exhibit improved physicochemical properties, showing their potential for development of new solid dosage forms.