Abstract
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.
Highlights
Diabetes is a progressive metabolic disorder that increases the prevalence of nonalcoholic fatty liver disease (NAFLD)
RH40 was added to the EZ micellar system (Figure 1B), the Scanning Electron Microscopy (SEM) micrograph showed a surfactant film covering the small crystals of EZ on the large croscarmellose particles
6 offilm identified by energy dispersive X-ray (EDX) analysis
Summary
Diabetes is a progressive metabolic disorder that increases the prevalence of nonalcoholic fatty liver disease (NAFLD) This hepatic damage is manifested in liver steatosis and inflammation of the hepatic cells. The accumulation of LDL and high values of transaminases such as alanine transaminase (ALT) and aspartate transaminase (AST) are indicative of significant hepatic steatosis in diabetic patients and are difficult to manage with current available therapies [1]. Animal models, such as Goto-Kakizaki (GK) rats are especially useful as models of diabetic dyslipidemia for the efficacy studies of different pharmacological treatments [2].
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