Preparation, Characterization and In vivo Evaluation of Rosuvastatin Calcium Loaded Solid Lipid Nanoparticles

Abstract


 Rosuvastatin calcium (RC), is a hypolipidemic drug, and has poor oral bioavailability of about 20% due to first-pass effect. For improving the oral bioavailability of RC, solid lipid nanoparticles (SLNs) were developed using triglycerides (tristearin, tripalmitin, and trimyristin). Hot homogenization followed by ultrasonication method was used to prepare RC-SLNs. The prepared SLNs were characterized for particle size, PDI, zeta potential (ZP), entrapment efficiency (EE) and drug content. In vitro release studies were performed in 0.1N HCl and pH 6.8 phosphate buffer of by open tube method. Physical stability the SLNs was observed at refrigerated temperature and room temperature for 60 days. Pharmacokinetics of RC- SLNs after oral administration, in male Wistar rats was studied. SLNs prepared with tristearin (Dyanasan-118) having size of 207.3 ± 8.52 nm, PDI of 0.344 ± 0.084, ZP of – 20.9 ± 4.88 mV with 97.06 ± 0.210 % EE were optimized. Differential scanning calorimetric (DSC) study revealed that no interaction between drug and lipid. In vitro release studies showed that more cumulative release of RC in pH 6.8 phosphate buffer than in 0.1NHCl during 24 hours. The lyophilized SLN formulation was used in knowing morphology of SLNs and was found to have spherical shape with increased polydispersity by Scanning electron microscopy. Pharmacokinetic studies showed the relative oral bioavailability of SLNs was 2.2 fold when compared to that of a suspension (p<0.001). Taken together, the results are indicative of SLNs as lipid based carriers for improving the oral bioavailability of this drug by minimizing first pass metabolism.