Title : Precisely fabricated monophasic sulpiride-naringin coamorphous system with ameliorated oral bioavailability and antidepressant activity
Abstract:
The study aimed to develop a supramolecular formulation of sulpiride (SUL) with naringin (NARI) to enhance its solubility, dissolution, and permeability, and P-glycoprotein (P-gp) efflux inhibition mechanisms. SUL is utilized to treat various conditions like gastric ulcers, migraines, and anti-emetic, anti-depressive, and anti-dyspeptic issues. NARI, a flavonoid, was chosen as a co-former due to its diverse biological activities, including anti-apoptotic, anti-oxidant, and anti-inflammatory properties. The study combined experimental techniques with computational approaches, including molecular dynamics (MD) simulation and density functional theory (DFT) studies, to investigate intermolecular interactions and phase transformations. Miscibility studies, radial distribution function (RDF) analysis, and molecular docking aided in understanding the amorphization aspects of the SUL-NARI supramolecular systems. Solubility, dissolution, and ex-vivo permeability studies demonstrated significant improvements with 31.88-fold, 9.13-fold, and 1.83-fold increments, respectively. Biological assessments showed superior neuroprotective effects in the SUL-NARI co-amorphous system compared to pure SUL. This comprehensive approach highlights the potential of drug-nutraceutical supramolecular formulations to enhance the solubility and permeability of SUL, offering novel treatment avenues for depression through experimental analysis. The pharmacokinetic analysis revealed an enhancement of SUL oral bioavailability with a co-amorphous system compared to SUL alone, along with Cmax improvement. Pharmacodynamic evaluation demonstrated superior antidepressant efficacy, and increases in serotonin and dopamine expression, respectively. Toxicological assessment confirmed SUL-NRG biocompatibility upon repeated oral administration.
