Cocrystals of Nitrofurantoin: How Coformers Can Modify Its Solubility and Permeability Across Intestinal Cell Monolayers

Solubility and permeability of nitrofurantoin (NITRO) were compared with those its cocrystals containing isoniazid (ISO), bipyridyl (BIP), or phenanthroline (PHE) as coformers, their parent mixtures. NITRO dissolution profiles evaluated via HPLC; we resorted to molecular dynamics (MD) simulations rationalize the experimental data on basis nitrofurantoin–coformers nitrofurantoin–water intermolecular interactions. Permeation studies performed by using an in vitro model small intestine based IEC-6 cells. The water solubility was reduced mixture PHE BIP but not ISO. Cocrystallization induced a slight increase solubility; cocrystallization decrease, even if lower than physical mixture. changes attributed solvation shell alterations (MD simulations). ISO allowed first 30 min pattern. measurements showed that NITRO–PHE detrimental for monolayer integrity, whereas no cocrystal. No effects integrity observed either NITRO–ISO NITRO–BIP cocrystal increased across without reducing integrity.