Pirfenidone–flavonoid cocrystals with reduced solubility and dissolution rate

Abstract

Pirfenidone (PFD) is an orally administered medication used for the treatment of idiopathic pulmonary fibrosis. PFD has excessive solubility and high daily dosage. A sustained-release solid form of PFD is desired to improve the rapid absorption and elimination of this highly soluble drug, as well as dose related side effects. Ketone⋯hydroxyl (CO⋯H–O) hydrogen bonding was employed as a heterosynthon for pharmaceutical cocrystal design. And two PFD–flavonoid cocrystals, PFD–hesperetin (PFD–HES, 1 : 1) and PFD–genistein (PFD–GEN, 2 : 1), were successfully obtained here. These two cocrystals were characterized by single crystal and powder X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and dynamic vapor sorption (DVS). Dissolution studies revealed that cocrystals have significantly reduced solubility and intrinsic dissolution rate (IDR) by orders of magnitude in pH 1.2 and 6.8 media, which would provide positive contribution to better drug performance of PFD.