Growth retardation of diflunisal in antisolvent crystallization

Diflunisal, an analgesic anti-inflammatory drug, was recrystallized from acetone solution using water and carbon dioxide as antisolvents. The crystallized diflunisal showed an acicular crystal habit with a very high aspect ratio. Growth retardation of diflunisal crystals was observed when ultrasound was added during the recrystallization and when habit-modifying agents were applied to the system. For example, an increase in sebacic acid concentration from 0.229 to 2.132 wt% lowered the aspect ratio of the crystal from 62 to 8.5, while an increase in Span 83 concentration from 1.712 to 4.415 wt% reduced the aspect ratio from 11 to 4.0. Differential scanning calorimetry and X-ray diffraction analysis revealed that the presence of ultrasound and habit-modifying agents may induce structural modifications as well as the growth retardation of diflunisal crystals.