Oleanolic acid (OA) ischaracterized by its low water solubility, poor permeability and majorly metabolized by cytochrome P450 (CYP) isozymes in the intestinal tract, particularly CYP3A, which contribute to the low oral bioavailability. OA has multiple pharmacological actions including hepatoprotective, anti-inflammatory, antidiabetic and antiviral effects. OA classified as a BCS IV drug which have restricted its potential clinical application. In this study D-α-Tocopheryl polyethylene glycol succinate (TPGS) and Pluronics F68 based stabilized OA loaded mixed micellar system (OA-MMs) developed to improve the solubility and permeability. Mixed micelles were characterized by dynamic light scattering studies as a function of temperature, salt addition, and OA solubilisation followed byXRD, FE-SEM and IR analysis confirmed the formation of stabilized OA-MMs with the least size and PDI (10.041 ± 1.35nm, 0.313 ± 0.012). Scattering studies results demonstrates the formation of stable micelles with no significant alterations insize upon salt addition (up to 150mM NaCl), OA incorporation (up to 150 mM) and temperature rise till 40°C.Solubility of the pure OA and OA-MMs was found to be 0.042mg/ml and 1.98mg/ml. The % cumulative release of drug from alone OA, OA + TPGS and OA-MMs was found to be 4.363 ± 0.025%, 57.18 ± 0.034% and 92.269 ± 0.017% respectively up to 24h. Single-pass intestinal perfusion studies (SPIP) showed that Ka and Peffective of OA-MMs was improved30 fold as compared with that of pure OA and this was mainly due to the improved permeability and inhibitory effect of Pluronic F68 on CYP3A. The in vivo Pharmacokinetic study showed that Cmax increased markedly from 12.76 to 20.49 and 39.17µg/ml in case of OA alone, OA + TPGS and OA-MMs. Parallel to the Cmax there was an increase in the AUC0-24133.68 to 164.56 and 296.50 respectively. All of the produced OA-MMs formulation's results demonstrated a notable increase in OA's bioavailability through increased permeability and solubility along with metabolic inhibition OA.
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