Pharmacodynamic Studies of Pravastatin Sodium Nanoemulsion Loaded Transdermal Patch for Treatment of Hyperlipidemia.

Pravastatin sodium (PVS) is a hypolipidemic drug with poor oral bioavailability due to the first-pass effect. Therefore, this study aims to formulate and evaluate transdermal patches containing PVS-loaded nanoemulsions (PVS-NEs) to increase PVS's hypolipidemic and hepatoprotective activities. PVS-NEs were prepared using the aqueous titration method, where oleic acid was chosen as an oil phase, and span 80 and tween 80 were used as surfactant and cosurfactant respectively. Droplet size (DS), polydispersity index (PDI), zeta potential (ZP), clarity, and thermodynamic stability of NEs were all characterized. Also, PVS-NEs (NE2) with 50% oil phase, 40% SC mix 2:1, and 10% water were selected as an optimum formula based on the results of DS (251 ± 16), PDI (0.4 ± 0.16), and ZP (-70 ± 10.4) to be incorporated into a transdermal patch, and PVS-NE2 loaded transdermal patches (PVS-NE2-TDPs) were prepared by solvent evaporation method. F1 patch with HPMC E15 and PVP K30 in a ratio of 3:1 represented satisfactory patch properties with good drug-excipients compatibility. Thus, it was selected as an optimum patch formula. The optimized F1 patch was characterized for thickness, moisture content, weight variation, and drug-excipients incompatibility. Therefore, it was subjected to ex vivo skin permeation and finally pharmacodynamic studies. Ex vivo permeation studies of F1 revealed that the cumulative amount of PVS permeated across rat skin was 271.66 ± 19 µg/cm2 in 72 h, and the pharmacodynamic studies demonstrated that the F1 patch was more effective in treating hyperlipidemia than PVS-TDP (control patch) based on both blood analysis and histopathological examination. .

Formulation and Evaluation of Pravastatin Sodium-Loaded PLGA Nanoparticles: In vitro-in vivo Studies Assessment.

Purpose: Pravastatin sodium (PVS) is a hypolipidemic drug which suffers from extensive first-pass metabolism and short half-life. Poly(d,l-lactide-co-glycolide) (PLGA) is considered a promising carrier to improve its hypolipidemic and hepatoprotective activities. Methods: PVS-loaded PLGA nanoparticles (PVS-PLGA-NPs) were prepared by double emulsion method using a full 32 factorial design. The in vitro release and the physical stability studies of the optimized PVS-PLGA-NPs (F5) were performed. Finally, both hypolipidemic and hepatoprotective activities of the optimized F5 NPs were studied and compared to PVS solution. Results: All the studied physical parameters of the prepared NPs were found in the accepted range. The particle size (PS) ranged from 90 ± 0.125 nm to 179.33 ± 4.509 nm, the poly dispersity index (PDI) ranged from 0.121 ± 0.018 to 0.158 ± 0.014. The optimized NPs (F5) have the highest entrapment efficiency (EE%) (51.7 ± 5%), reasonable PS (168.4 ± 2.506 nm) as well as reasonable zeta potential (ZP) (-28.3 ± 1.18mv). Solid-state characterization indicated that PVS is well entrapped into NPs. All NPs have distinct spherical shape with smooth surface. The prepared NPs showed a controlled release profile. F5 showed good stability at 4 ± 2°C during the whole storage period of 3 months. In vivo study and histopathological examination indicated that F5 NPs showed significant increase in PVS hypolipidemic as well as hepatoprotective activity compared to PVS solution. Conclusion: The PVS-PLGA-NPs could be considered a promising model to evade the first-pass effect and showed improvement in the hypolipidemic and hepatoprotective activities compared to PVS solution.