Optimized Nanoparticles for Enhanced Oral Bioavailability of a Poorly Soluble Drug: Solid Lipid Nanoparticles Versus...

Rosuvastatin calcium (ROSCa) is an anti-hyperlipidemic drug with only 20% oral bioavailability due to its low solubility and high first-pass metabolism. Therefore, the main purpose of this work was to compare solid lipid nanoparticles to nanostructured lipid carriers and evaluate their effect on solubility improvement and hence the bioavailability of a model insoluble drug.

Different nanosuspensions were formulated using high-speed homogenization and ultrasonication techniques, using Apifil as solid lipid and Maisine as liquid lipid. The effect of different variables on quality attributes (particle size, entrapment efficiency (EE), and in vitro release) was studied using the Box-Behnken design. Then, the optimized nanoparticles were lyophilized, filled into capsules, and evaluated. Finally, the optimized formula was clinically evaluated in six healthy human volunteers.

It was observed that the variables had a great impact on EE and particle size. Nanoparticles showed maximum particles of 180.3 nm, and % EE ranged from 40.77% to 91.67%. Capsules loaded with NLCs were found to be more stable than those loaded with SLNs. The clinical study of NLCs-ROSCa showed an enhancement in the C max (8.92 ng/ml) compared to the commercial product (2.56 ng/ml) with approximately 349% relative bioavailability.

ROSCa was successfully encapsulated in SLNs and NLCs. The optimized NLCs formulation showed improved quality attributes compared to SLNs. Thus, NLCs loaded formulations could be an effective oral drug delivery system to enhance the bioavailability of insoluble drugs.