| Solid lipid nanoparticles(SLN)is an alternative carrier system with solid biodegradable lipid as drug carriers, diameters ranging between 10 nanometers to 1000 nanometers, which has the advantages of high physical stability, more entrapment efficiency(EE), controlled drug release and sustained release, more bioavailability comparing to other transdermal preparations. It also has the advantages of low speed of leakage, low cytotoxity, large scale production, etc. This article took how to improve the transdermal permeability of pooly water-solution Huperzine A as the main body mentality, prepared solid lipid nanoparticles loading Huperzine A for transdermal delivery,and had conducted the research to its in vitro transdermal penetration.During the preformulation study, an HPLC method with 0.02M KH2PO4 solution (pH 3.90)/ acetonitrile (86:14) as mobile phase was developed for the assay of the drug, which was simple and reliable. And drug solubility and oil/water partition coefficient were determined in different media, which showed that Huperzine A was high lipid solubility and suitable for preparation of SLN. Meanwhile, the preliminary research of in vitro transdermal penetration was studied to lay a foundation for the penetration behavior of Huperzine A-SLN.According to the results of the preformulation study, the method of hot high pressure homogenization technique was used to prepare Hup A-SLN. The particle size, entrapment efficiency and stability were taken as criterions to evaluate the effects of different type and amount of lipid materials and surfactant mixture. And then used the fixed formula to investigate emulsifying temperature, stirring time and stirring rate which would affect the quality of Hup A-SLN. On the basis of the single factor exploration , the satisfactory formulation was selected by orthogonal design with high entrapment efficiency as standard. The results of the satisfactory formulation were as follows:the particle size was 31.6±1.6nm, the entrapment efficiency was73.26±1.30%.The properties of Hup A-SLN were studied in detail in order to make sure the quality of it. The surface morphology of SLN was observed by transmission electron microscope, the particle size and Zeta potential of SNL were determined by a Zetasizer 3000HS nanometer laser particle size analyzer. Dialysis and ultrafiltration these two entrapment efficiency methods were compared. A preliminary stability of Hup A-SLN was also studied, results indicated that Hup A-SLN kept at room temperature (25℃) , the appearance of two months after placement, the average particle size, Zeta potential and entrapment efficiency and so on which related to physical and chemical properties were stable, while at low temperature (4℃) storage conditions, the stability was poor.Because freeze-dried not only solved the long-term stability problem of SLN, but also could be used to prepare other kind of Huperzine A formulation. Hup A-SLN freeze-dried process was studied in this paper. The different sugars cryoprotectents on the appearance,the mean particle size and redispersibility in SLN after freeze-dried were investigated to choose the optimum cryoprotectent。After that freeze-drying process was optimized. Hup A-SLN freeze-dried product prepared by optimized lyophilized was solid block of with homogeneous white light and the appearance was full. After room temperature (25℃) environment for 3 months, it showed good stability.Finally, Hup A-SLN in vitro transdermal penetration was studied by comparing the skin permeability of Hup A-SLN, Hup A-SLN gel and Huperzine A. The results showed that the skin permeability of Hup A-SLN and Hup A-SLN gel were superior to raw materials, and the higher the drug content was, the better the transdermal capacity was.
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