Facile Formulation of an Oral Nanovesicular Carrier Co-Encapsulating Simvastatin and Ezetimibe for Enhanced...

Simvastatin/Ezetimibe (SIM/EZE) is a widely prescribed hypolipidemic drug combination that provides substantial cardiovascular protection, particularly in high-risk patients. However, its poor dissolution and extensive first-pass metabolism limit gastrointestinal bioavailability, necessitating higher doses and thereby increasing the risk of adverse effects. In this study, we report a facile, robust, and easily scalable cholesterol-surfactant based nanocarrier system to enhance the oral delivery of SIM/EZE. Nanoparticles were prepared using Span 60 or Tween 80 in combination with cholesterol and optimized via a 2³ factorial experimental design. The effects of surfactant type, surfactant-to-cholesterol ratio, and sonication time on formulation characteristics were systematically investigated. The optimized formulation, prepared with 1200 mg Span 60, 300 mg cholesterol, 40 mg SIM, and 10 mg EZE and sonicated for 40 min, exhibited spherical morphology, a small particle size (109.6 nm), a zeta potential of (-37.91 mV), and high encapsulation efficiency (97.39 % for SIM and 88.79 % for EZE). Stability testing confirmed the absence of degradation under physiological conditions and showed no significant changes over three months of storage. In vivo evaluation in a hyperlipidemic rat model demonstrated that the optimized formulation significantly reduced total cholesterol levels compared with both the marketed product (Inegy™) and the drug suspension, indicating enhanced oral absorption. These findings highlight the potential of this nanoparticle system as an effective platform to improve the therapeutic efficacy of the SIM/EZE fixed-dose combination.