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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.

Molecular docking is a resourceful virtual screening tool for predicting the possible therapeutic activities of molecules and lowering the attrition rate at the early stage of drug design and development. Recently reports of molecular docking of cocrystals have been published to demonstrate their potential biological activities toward specific target proteins. Since regulatory bodies, e.g., U.S. FDA and EMA, do not identify cocrystal as a new molecular entity, it is not relevant to conduct such docking studies, especially in the case of orally administered cocrystals, by posing them as ligands instead of the parent API. This article showcases the noteworthy considerations regarding molecular docking studies of cocrystals as ligands.

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