LAUSR

&NA; The intent of this investigation was to improve pharmacokinetic (PK) and pharmacodynamic (PD) effects of Rosuvastatin calcium (RC) by solid lipid nanoparticles (SLNs). RC is anti‐hyperlipidemic drug with low oral bioavailability (20%) due to first‐pass metabolism. Hot homogenization followed by ultrasonication method was used to prepare RC‐SLNs with stearic acid, glyceryl behenate and glyceryl trilaurate as lipid matrices, egg lecithin and poloxamer 188 as surfactants. The prepared SLNs were tested for particle size, PDI, zeta potential (ZP), entrapment efficiency (EE), drug content and in vitro release. Further, PK and PD studies were conducted on selected SLNs. No changes in physical stability of the optimized SLN were observed at refrigerated and room temperature for 90 days. SLNs prepared with glyceryl trilaurate having average size of 67.21 ± 1.71 nm, PDI of 0.25 ± 0.01, ZP of −28.93 ± 0.84 mV with 93.51 ± 0.34% EE was considered as optimized. DSC and XRD studies revealed that no interaction occurred between the drug and lipid. SEM and TEM studies revealed that SLNs were nearly spherical in shape. PK studies showed improvement in the oral bioavailability (extent of absorption) of SLNs by 4.6‐fold when compared to that of suspension. PD study of SLNs in hyperlipidemic rats exhibited a decrease in lipid profile for 36 h, while a suspension exhibited for 24 h. Graphical abstract Figure. No caption available.