Impact on HDL and LDL of Hyperlipidemic Rat Models: Designed Solid Self-Nanoemulsifying Drug Delivery Systems with Atorvastatin and Ezetimibe combination

Abstract

The main purpose of this study was to develop and evaluate solid self-nanoemulsifying drug delivery systems (S-SNEDDs) of Atorvastatin/ Ezetimibe combination to combine the advantages of liquid SNEDDs with those of solid dosage forms and investigate the effect of solidification on both lipid lowering efficiency and the ability to enhance oral bioavailability of included poorly water soluble drugs. Spray dried solid powder was prepared using Aerosil 200 based on its high adsorption capacity and the ratio of liquid SNEDDs: Aerosil was (4:1) due to the smaller droplet size produced after reconstitution compared to other ratios. Surface morphology characteristics and drug-excipients interactions were evaluated via Scanning Electron Microscopy (SEM) and Fourier Transformed Infrared Spectroscopy (FTIR). Crystallinity nature affect drug dissolution so, it was determined by Differential Scanning Calorimetry (DSC) and Powder X-ray Diffraction (PXRD). Pharmacokinetic study investigated the ability of (S-SNEDDS) to improve oral bioavailability of included drugs while, pharmacodynamic study evaluate its efficiency to control serum cholesterol levels compared to pure drugs suspension and liquid SNEDDs. Solid spray dried powder showed very good flowability (3.41±0.23g/s) and rapid dispersion in water with maintaining the self-emulsifying efficiency of liquid formula. Physicochemical evaluation of powder showed spherical separated particles with no significant drug-excipients interactions and drugs are molecularly dispersed or in amorphous state that improve dissolution rate as proven by in-vitro release studies. Pharmacokinetic and pharmacodynamic studies proved that the solidification process had no remarkable effect on the efficiency of liquid formula to enhance oral bioavailability of incorporated drugs and control serum cholesterol level compared to pure drugs suspension. S-SNEDDS was proved as efficient candidate to improve oral bioavailability of Atorvastatin / Ezetimibe combination and control cholesterol serum levels.