Pharmaceutical Cocrystals of Diflunisal and Diclofenac with Theophylline

Pharmaceutical cocrystals of nonsteroidal
anti-inflammatory drugs
diflunisal (DIF) and diclofenac (DIC) with theophylline (THP) were
obtained, and their crystal structures were determined. In both of
the crystal structures, molecules form a hydrogen bonded supramolecular
unit consisting of a centrosymmetric dimer of THP and two molecules
of active pharmaceutical ingredient (API). Crystal lattice energy
calculations showed that the packing energy gain of the [DIC + THP]
cocrystal is derived mainly from the dispersion energy, which dominates
the structures of the cocrystals. The enthalpies of cocrystal formation
were estimated by solution calorimetry, and their thermal stability
was studied by differential scanning calorimetry. The cocrystals showed
an enhancement of apparent solubility compared to the corresponding
pure APIs, while the intrinsic dissolution rates are comparable. Both
cocrystals demonstrated physical stability upon storing at different
relative humidity.