Investigating the Role of the Reduced Solubility of the Pirfenidone–Fumaric Acid Cocrystal in Sustaining the Release Rate from Its Tablet Dosage Form by Conducting Comparative Bioavailability Study in Healthy Human Volunteers

Pirfenidone (PFD) is the first pharmacological agent approved by the US Food and Drug Administration (FDA) in 2014 for the treatment of idiopathic pulmonary fibrosis (IPF). The recommended daily dosage of PFD in patients with IPF is very high (2403 mg/day) and must be mitigated through additives. In the present work, sustained-release (SR) formulations of the PFD-FA cocrystal of two different strengths such as 200 and 600 mg were prepared and its comparative bioavailability in healthy human volunteers was studied against the reference formulation PIRFENEX (200 mg). A single-dose pharmacokinetic study (200 mg IR vs 200 mg SR) demonstrated that the test formulation exhibited lower C_max and T_max in comparison to the reference formulation, which showed that the cocrystal behaved like an SR formulation. Further in the multiple-dose comparative bioavailability study (200 mg IR thrice daily vs 600 mg SR once daily), the test formulation was found bioequivalent to the reference formulation. In conclusion, the present study suggests that cocrystallization offers a promising strategy to reduce the solubility of PFD and opens the door for potential new dosage forms of this important pharmaceutical.