Fabrication of a modafinil co-crystal for enhanced dissolution, anti-depressant potential and density functional...

In the current study, a modafinil (MO)-based co-crystal of MO-BA with benzoic acid (BA) as the co-former was prepared. The MO-BA formation was confirmed experimentally by FT-IR spectroscopy, DSC, and PXRD and elucidated theoretically via density functional theory (DFT). The broadening, shifting and attenuation of the -OH, -NH, -C[double bond, length as m-dash]O and -S[double bond, length as m-dash]O peaks in the FT-IR spectra confirm the synthesis of the MO-BA co-crystal. The appearance of endothermic peaks at different temperatures for MO-BA (112 °C) compared with MO (166 °C) and BA (122 °C) indicated the effective formation of MO-BA. Similarly, the diffractogram of MO-BA exhibited peaks with different 2θ values from those of MO and BA in terms of position as well as intensity. These fluctuations in diffraction patterns support the formation of a new crystalline phase. HPLC analysis showed that MO and BA combine in a 1 : 1 ratio to form MO-BA. QTAIM analysis revealed the presence of strong hydrogen bonding and van der Waals interactions, as evidenced at bond critical points based on Laplacian density, electron density and total energy density. The in vitro dissolution profiles of the MO-BA co-crystal and raw MO were found to be 51.75% ± 1.55% and 31.42% ± 1.48% in buffer solutions of pH 6.8 and 59% ± 1.20% and 37.61% ± 1.85% in acidic HCl medium of pH 1.3, respectively. The in vivo anti-depressant potentials of raw MO and MO-BA were evaluated by the forced swim test (FST) and tail-suspension test (TST). The observed immobility responses of MO and MO-BA at a dose of 30 mg kg^-1 were 95.83 ± 1.13 and 89.66 ± 1.78 s in the FST and 119.16 ± 1.42 and 114.66 ± 1.58 s in the TST, respectively. This study provides insights into the effective formation of the MO-BA co-crystal with enhanced dissolution and improved anti-depressant potential compared with pristine MO, offering excellent bioavailability.