Study On Solid Lipid Nanoparticles For Vinpocetine Injection

Among modern drug delivery carriers solid lipid nanoparticles (SLN) is a promising colloidal carrier system. The diameter range of solid lipid nanoparticles which were made from biodegradable solid lipids is between 50 and 1000 nanometers. The advantages of SLN are as follows:possibility of delayed release、controlled drug release and drug targeting, protection of incorporated compound against chemical degradation, slow speed of drug leakage and low toxicity etc. Vinpocetine is an agent to improve cerebral circulation The objective of this thesis is to study Vinpocetine-loaded solid lipid nanoparticles(SLN) for intravenous administration.The method of High Pressure Liquid Chromatography(HPLC) was established to assay vinpocetine in the preformulation study. The equilibrium solubility and the oil-water distribution coefficient of vinpocetine in different pH solutions were inspected and the equilibrium solubility of vinpocetine in pH 7.4 phosphate buffer with different concentration of Tween80 and the stability of vinpocetine during storage were characterizedAccording to the results of preformulation study, an emulsify-ultrasounding method was developed to prepare VIN-SLN,with Compritol 888 ATO as a lipid carrier. The assay method of vinpocetine incorporation efficiency and drug loading capacity was constructed. The optimal formulation was obtained by the single factor of exploration and orthogonal design, while the particle diameter, incorporation efficiency and stability were set as indexes.The characteristics of the optimal VIN-SLN were characterized.The morphology of the VIN-SLN prepared according to the optimal formulation was spheroidal and homeo-spheroidal using a transmission electron microscopy.The mean particle diameter of VIN-SLN was 155.8±12.2nm..Its incorporation efficiency and drug-loaded capacity was (94.37±1.24)% and (2.70±0.04)%, respectively.Its pH was about 6.7. In the in-vitro release study, the accumulation release percentage of VIN-SLN was 71.84% for 72h, fitting Higuchi linear equation. The stability of the vinpocetine in the model SLN was stable when being kept at 4℃for two month. The VIN-SLN were successfully lyophilized in order to increase their stability. The particle diameter and incorporation efficiency were investigated before and after the freeze-drying of VIN-SLN. The freeze-dried VIN-SLN powders were investigated by Differential Scanning Calorimetry(DSC) and X-ray diffraction method. Meanwhile, the crystal structure change of materials in VIN-SLN was studied, which illustrated that VIN was packed in SLN.An method of HPLC was developed for the determination of VIN in rat plasma. Setting rats as animal model, the pharmacokinetics of commercial VIN injection and VIN-SLN were studied. The results showed that the average AUC0-∞of SLN group was 6870.912 ng-h-mL-1, while 2979.994 ng-h-mL-1 of control group,2.31 times of control group. The elimination rate constant, Ke, of SLN group was 0.112 h-1, lower than 0.913 h-1 of control group. The T1/2 of SLN was 6.208h, which was obviously higher than 0.759h of control group.The residence time of VIN from VIN-SLN in rats plasma was extended and its elimination was slower, presenting slow-release result.