Response surface guided design of lipid-polymer hybrid nanoparticles for dual delivery of rosuvastatin and ezetimibe

software. Four optimal formulations were developed, with acid-terminated polymer and 1,2-dioleoyl-3-trimethylammonium-propane chloride, minimized particle size (229-240 nm) and polydispersity index (0.150-0.237), maximized total drugs loading (up to 7.44%) and neutral zeta potential (within ± 10 mV), having successfully loaded rosuvastatin and ezetimibe in ratio of 1, 1.5, 2 and 2.5, with potential for its modulation based on lipid to polymer ratio. Optimal formulations with suitable biopharmaceutical and physicochemical properties for oral administration were obtained, showing sustained drugs release over 36 h (in pH 6.8 and 7.4) and stable colloidal behavior over three-month storage. SEM revealed spherical morphology and size consistent with DLS measurements.FTIR, DSC and TGA confirmed nanoparticles stability and gave valuable insight into the drug-excipient interactions. XRPD analysis confirmed drugs encapsulation in an amorphous state. The optimized formulations may serve as a promising platform for future development in hyperlipidemia therapy.