Impact of adsorption-based solidification on the pharmaceutical performance and antidyslipidemic efficacy of simvastatin-ezetimibe SNEDDS.

Simvastatin and ezetimibe are widely used in combination therapy for dyslipidemia; however, their poor aqueous solubility limits oral bioavailability. This study aimed to develop and characterize liquid and solid self-nanoemulsifying drug delivery systems (L-SNEDDS and S-SNEDDS) containing simvastatin and ezetimibe and to evaluate the impact of adsorption-based solidification on their physicochemical characteristics, dissolution behavior, and antidyslipidemic efficacy. An optimized L-SNEDDS composed of Capryol® 90, Cremophor® RH40, and Transcutol® HP was successfully converted into S-SNEDDS by adsorption onto Neusilin® US2. The optimized L-SNEDDS exhibited rapid self-emulsification, high transmittance, and a globule size of 24.47 ± 0.55 nm, whereas S-SNEDDS readily reconstituted into a nanoemulsion with a globule size of 35.51 ± 0.32 nm. Adsorption-based solidification did not alter the chemical integrity of either drug and maintained both drugs predominantly in an amorphous or molecularly dispersed state. S-SNEDDS markedly increased the apparent solubility of both drugs, and both formulations substantially enhanced drug dissolution compared with the drug suspension, although dissolution from S-SNEDDS was slightly lower than that from L-SNEDDS. In a Poloxamer 407-induced dyslipidemia model, both formulations significantly reduced total cholesterol, LDL-C, and triglyceride levels compared with the dyslipidemic control and produced greater lipid-lowering effects than the drug suspension, while no significant differences were observed between L-SNEDDS and S-SNEDDS. These findings suggest that adsorption-based solidification preserved the pharmaceutical and therapeutic performance of the optimized L-SNEDDS while providing the practical advantages of a solid dosage form, supporting S-SNEDDS as a promising oral lipid-based delivery system for simvastatin-ezetimibe combination therapy.