Studies On Nanoparticles Of Lovastatin For Oral Administration

Because of the insolubility, the less absorption and the first pass effect of some insoluble drug, the oral bioavailability of those drugs is extremely low. The nano-technology is employed to improve the oral bioavailability of the insoluble drug and the perspective of the combination of the drug and the nano-technology is very promising. The main principle of the nano-technology which can resolve the bioavailability is that the retention of the drug in the gastrointestinal tract can be extended, the total of the dissolution can be increase and the drug can be absorbed through lymph circulation by which the fist pass effect can be decrease. In order to improve the oral bioavailability of the insoluble drug, the formulations of polymer nanoparticle and the solid lipid nanoparticle with lovastatin (LV) as a model drug were studied.The nanoprecipitation method was employed to prepare LV-PLGA nanoparticle (LV-PLGA-NP), the volume ratio of water to acetone, the weight ratio of PLGA to lovastatin, the concentration of lovastatin in acetone were key factors for the preparation of LV-PLGA-NP. The central composite design with the criteria of OD was performed to optimize the process parameters after the single-factor investigation. Many physiochemical characteristics of LV-PLGA-NP were investigated. The appearance of LV-PLGA-NP was global particle with mean size of 122 nm, the Zeta potential was-11.7 mv, the drug load effect and the encapsulation efficiency were 2.30% and 81.16%, respectively.Results of the release experiments indicated that the release rate of LV from LV-PLGA-NP accorded with both Higuch and Weibull equation with obviously delayed release.The conclusion that the drug might be embed in the LV-PLGA-NP can be supposed from the release experiment.The solvent diffuse-emulsification-cool solidify method was used to prepare the LV-SLN. The main disadvantages of SLN include the low drug loading capacity and the drug leakage during storage period induced by the conversion of crystal of the lipid. The main point of the article is resolve these problems of SLN and the conception of crystallization-inhibitor was first introduced.A acrylic resin was successfully selected by the experiment.The formulation components and the manufacture factors were optimized by orthogonal design with the criteria of physical stability and the pharmaceutical properties of sample were also evaluated.The result indicated that the concentration of the surfactant and lipid, the weigh ratio of lipid to drug and the weight ratio of lipid to crystallization-inhibitor could affect the physical stability of SLN.The appearance of LV-SLN was irregular global particle with mean size of 156 nm, the Zeta potential was-10.08 mv, the drug load rate and the encapsulation efficiency were 7.93% and 99.26%,respectively.Results of the release experiments indicated that the release rate of LV from LV-SLN accorded with Weibull equation with obviously delayed release.DSC and X-ray was employed to investigate the effect of acrylic resin to the crystal form of lipid and the drug, the crystal conversion of the lipid along with time was also study. The crystallization form of the drug embedded in the SLN is amorphous. The acrylic resin prohibit the conversion of the crystallization form of the lipid successfully,at the same time the advantage such as low drug load capacity and the leakage of drug during storage time were also be resolved. The mechanism of the encapsulation and the release of the drug in SLN were investigated by the release experiments. the result indicate that the drug may exist in the form of solid solution and the drug release may induced by the dissolve of acrylic resin and the corrosion of the lipid.In order to investigate the store stability of SLN the sample with different content of acrylic resin was placed in 4℃and 25℃, respectively.The result indicate that the SLN store in 25℃was more stable than that in 4℃and the stability of SLN increased with the increase of acrylic resin in the formulation.An HPLC method was developed for the determination of LV in the plasma of rats. the method that extract the drug from the plasma is extremely higher than others handed under the same condition. Oral pharmacokinetic behaviors of LV-suspension and LV-SLN were investigated in rats. The software of DSA2.0 was employed to operate the parameters, According to the concentration of LV-time curve,the Tmax of LV from samples of suspension and SLN were 2.5h and 3.0h.and Cmax were 520.660 ng/ml and 746.044 ng/ml, respectively. The AUC of SLN is 2.019 times as that of the suspension formulation, this indicated that compared with the suspension the LV-SLN enhanced the oral bioavailability significantly.