Synthesis, Density Functional Theory Analysis and Dissolution Study of Non‐Covalent Derivatives of Modafinil

ABSTRACT In this study, Modafinil (MO) based co‐crystals with co‐formers Adipic Acid (AA) and Tartaric Acid (TA) were prepared, denoted as MO‐AA and MO‐TA, elucidated experimentally by FTIR, DSC, TGA, and PXRD, and confirmed theoretically via density functional theory (DFT). Shifting, attenuation, and broadening of the –OH, –NH, and C = O peaks in FTIR spectra and emergence of endothermic peaks at different temperatures of MO‐AA (140°C) and MO ‐TA (132°C) relative to MO, TA and AA indicated successful formation of the co‐crystals. Similarly, the thermograms and diffractograms of MO‐AA and MO‐TA also showed different behavior than MO and the co‐formers. However, the observed bond‐critical points (BCPs) along O(19)⋅⋅⋅H(54) and H(34)⋅⋅⋅O(44) interactions in MO‐AA, whereas H(34)⋅⋅⋅O(41), H(34)⋅⋅⋅O(43), and O(19)⋅⋅⋅H(50) interactions in MO‐TA, in addition to their Laplacian “∇ 2 ρ (r)”, and energy‐density “H(r)” values, divulged the existence of non‐covalent interactions, leading to co‐crystals. This study provides insights into effective formation of MO‐TA and MO‐AA co‐crystals, having enhanced dissolution offering excellent bioavailability.