Multiparticulate systems of ezetimibe micellar system and atorvastatin solid dispersion efficacy of low-dose ezetimibe/atorvastatin on high-fat diet-induced hyperlipidemia and hepatic steatosis in diabetic rats

The aim of this study was to develop multiparticulate systems with a combination of ezetimibe micellar systems and atorvastatin solid dispersions using croscarmellose as a hydrophilic vehicle and Kolliphor RH40 as a surfactant. The presence of a surfactant with low hydrophilic polymer ratios produces the rapid dissolution of ezetimibe through a drug-polymer interaction that reduces its crystallinity. The solid dispersion of atorvastatin with low proportions of croscarmellose showed drug-polymer interactions sufficient to produce the fast dissolution of atorvastatin. Efficacy studies were performed in diabetic Goto-Kakizaki rats with induced hyperlipidemia. The administration of multiparticulate systems of ezetimibe and atorvastatin at low (2 and 6.7 mg/kg) and high (3 and 10 mg/kg) doses showed similar improvements in levels of cholesterol, triglycerides, lipoproteins, alanine transaminase, and aspartate transaminase compared to the high-fat diet group. Multiparticulate systems at low doses (2 and 6.7 mg/kg of ezetimibe and atorvastatin) had a similar improvement in hepatic steatosis compared to the administration of ezetimibe and atorvastatin raw materials at high doses (3 and 10 mg/kg). These results confirm the effectiveness of solid dispersions with low doses of ezetimibe and atorvastatin to reduce high lipid levels and hepatic steatosis in diabetic rats fed a high-fat diet.