Nanoemulsion-Based Delivery of Ricinoleic Acid Derived from Terminalia chebula: A Novel Strategy for Enhanced Bioavailability and Preclinical Constipation Management

Abstract Constipation is a prevalent gastrointestinal disorder that significantly impacts quality of life. Ricinoleic acid, a potent stimulant laxative isolated from the dried fruit of Terminalia chebula, demonstrates significant pharmacological activity, although its therapeutic potential is limited due to poor aqueous solubility and low oral bioavailability. In this study, a nanoemulsion-based drug delivery system was developed and optimized to enhance the solubility, physicochemical stability, and therapeutic efficacy of ricinoleic acid. Formulation parameters including surfactant blend concentration, homogenization pressure, and number of homogenization cycles were optimized using a Box-Behnken experimental design. The optimized nanoemulsion exhibited a mean droplet size of 263.8 nm, a zeta potential of - 0.35 mV, and an entrapment efficiency of 81.5%. In vitro dissolution studies confirmed improved drug release following first-order kinetics. The in vivo laxative efficacy was evaluated using a loperamide-induced constipation model in Wistar rats. Animals treated with the nanoemulsion (50 mg/kg) showed a fecal water content of 55%, which was significantly higher than the disease control group (43%) and comparable to the standard laxative bisacodyl (65%). These findings support the potential of nanoemulsion-mediated delivery as a viable preclinical approach for enhancing the oral bioavailability and therapeutic outcome of ricinoleic acid in the management of constipation. Further preclinical and clinical investigations are warranted to validate its translational applicability.