The present study was carried out to investigate the antioxidant effect of ascorbic acid on omeprazole (O.P.)-induced acute kidney infection (AKI). Design of experiment (DoE) was employed to fabricate formulations (P1-P8) by the extrusion spheronization technique, and they were evaluated using various analytical techniques. P1-P8 formulations have % drug loading ranging from 56.34 ± 1.10 to 98.67 ± 1.05%, encapsulation efficiency from 70.98 ± 0.96 to 98.67 ± 1.05%, percentage drug release varying from 36.56 ± 1.34 to 93.45 ± 1.45%, Hausner's ratio ranging from 1.026 ± 0.05 to 1.065 ± 0.02%, and Carr's index varying from 2.3 ± 0.07 to 6.1 ± 0.06 g/mL. The optimized formulation (P6) was dual-coated with Eudragit L-100 (5% w/v) and ascorbic acid (2% w/v). A smooth uniform morphology was found after coating, and particle size nonsignificantly changed from 85.31 ± 77.43 to 101.99 ± 65.56 μm. IR spectra showed omeprazole characteristic peaks confirming drug loading, and peaks at 1747.40 and 1611.51 cm-1 confirmed ascorbic acid and Eudragit L-100 coating. X-ray diffraction (XRD) analysis confirmed the crystalline nature, and thermal degradation studies until 500 °C demonstrated increased stability after coating. Cytotoxicity analysis with 97% cell viability revealed the nontoxic behavior of pellets. In vitro dissolution studies of coated pellets showed <20% drug release at pH 1.2 and 99.54% at pH 6.8. Animal studies showed that pure omeprazole showed a nonsignificant decrease in weight, urine output, and fecal output compared to rodents on ascorbic acid pellets. Increased uric acid and creatinine levels in the group on pure omeprazole indicated AKI. Histopathological studies of renal cells also supported these results. The integration of experimental pellet formulation with molecular docking simulations has unveiled the potential of ascorbic acid and omeprazole as highly promising therapeutic agents for addressing oxidative stress and inflammation.
© 2023 The Authors. Published by American Chemical Society.