Mixed micellization of bile salts and transglycosylated stevia and enhanced binding and solubility of non-steroidal anti-inflammatory drugs using mixed micelle

This research investigated the efficacy of mixed micellar systems as an innovative chemical means of improving the binding properties of poorly water-soluble drugs. The formulations based on the mole fraction were used to prepare mixed micelles using anionic sodium deoxycholate (NaDC) or sodium cholate (NaC), and nonionic transglycosylated stevia (Stevia–G). Surface tension and dynamic light scattering (DLS) assessed the characteristic of the NaDC–Stevia–G and NaC–Stevia–G mixed micelles. Rubingh approach evaluated the interaction parameter (−β_m), which demonstrated synergistic interaction between the anionic and non-ionic surfactant. Mixed micelle was used to assess the binding constant (K_b) and solubility of non-steroidal anti-inflammatory drugs, ethenzamide (ETZ), and ibuprofen (IBF). K_b values increased, but the mean occupancy (i) of ETZ and IBF per micelle decreased by increasing α_Stevia–G 0.1 to 0.9, predicting a shift in occupancy of drugs from Palisade to Stern layer. At α_Stevia–G 0.9 the maximum solubility of ETZ and IBF was 7.50 and 2.60 mmolL⁻¹ for NaDC–Stevia–G and 5.60 and 1.70 mmolL⁻¹ for NaC–Stevia–G. To get a better comprehension about micellization behavior and preferential interaction of the drugs under study, quantum chemical calculations and molecular dynamic (MD) simulations were performed. The MD analysis assessed that the poorly water-soluble drugs demonstrated strong binding in the presence of NaDC–Stevia–G as compared to NaC–Stevia–G mixed micelle. Ultimately, in pharmaceutical applications, mixed micelle of bile salts-Stevia-G can be used as an effective drug solubilizing agent.