Preparation And Characterization Of Lovastatin-loaded Polymeric Nanoparticles

Lovastatin has been used as an inhibitor of HMG-COA deoxidization enzyme. Due to its poor water solubility and absorption after oral administration, low bioavailability limits its clinical therapeutic effect. However, the polymeric nanoparticles can improve the bioavailability of poorly soluble drugs. Therefore, polymer PLA and PLGA are selected as the carriers to prepare lovastatin polymeric nanoparticles, in order to increase the absorption, dissolution and bioavailability of lovastatin.The HPLC method was developed for the assay and the gradient elution method was established for the related substances of lovastatin polymeric nanoparticles. After the methodological validation, the method was accurate, reliable and applicable to the quality control of the product in vitro.The emulsion-solvent evaporation technique was employed to prepare lovastatin polymeric nanoparticles. Then the optimized preparation conditions were obtained, the ratio of lovastatin and polymer1:8, polymer concentration4%, PVA concentration2%, the ratio of organic phase1:10. The lovastatin polymeric nanoparticles were characterized. The results of characterization indicated that lovastatin polymeric nanoparticles had a mean particle size of200nm with a narrow size distribution. The chemical structure of lovastatin was not changed and amorphous lovastatin might be entrapped in the nanoparticles. Furthermore, dynamic dialysis method was used to determine the releasing characteristic of the nanoparticles in vitro, the release rate of the nanoparticles showed a significant increase and obvious sustained-release.The HPLC analysis method of stability was established and stability of lovastatin PLGA nanoparticles was then investigated. The results of stability tests show that the quality of it was stable.In the subject, a HPLC method was established to determine plasma concentration of lovastatin. The rats as experimental animals and lovastatin tablets as reference preparation with a single dose test. The in vivo pharmacodynamics study showed that the lovastatin-loaded PLA nanoparticles for i.m. injection could extend the retention time and improve the absorption of lovastatin in rat.