Study On Freeze-drying Submicroemulsion Of Vinpocetine

Studying and treatment on cerebrovascular disease (CVD, CVA) is one of the most important responsibilities in modern nerve rehabilitation science. From recent years'global death report, it indicated that circulation system disease, tumor and respiratory system disease become the main causes of people death.Cerebrovascular disease of circulation system diseases is becoming common ailment and frequently-occuring disease among the aged populations, of which the cerebral ischemia is main cause of death and is about70%~80%. Therefore, many attentions have been put on the study of anti cerebral ischemia drugs.Vinpocetine is a vasoactive vinca alkaloid and a synthetic derivative of apovincamine which has been used in clinical practice for the treatment of disorders arising from cerebrovascular and cerebral degenerative diseases. Vinpocetine is thought to increase the cerebral flow in the ischemic areas of patients with cerebrovascular disease, decrease platelet aggregability in patients with transient ischemic attack or stroke, increase red blow cell deformability in stroke patients, and have neuroprotective abilities and a protective effect against brain ischemia.Intravenous emulsion made by high pressure homogenization is a type of o/w emulsion which normally contains vegetable oil as oil phase and refining natural phospholipid as emulsifier. Fat emulsion has been used as a parenteral nutrition agent. As the needs of clinical treatment and development of pharmacy, the intravenous fat emulsion has gradually become a new type of drug delivery system.Objective: In this study, we selected the vinpocetine as the model drug and prepared the submicroemulsion of vinpocetine.Methods and Results:1,Preformulation study of vinpocetine submicroemulsion: A sensitive, precise and convenient HPLC method with high specificity for vinpocetine determination has been developed, which was not only suitable for vinpocetine content determination, but also suitable for the isolation of vinpocetine and its degradation products or other impurities.2,Formulation design of vinpocetine submicroemulsion and the research of preparation techniques: The formulation and preparation process were studied and evaluated with particle size distribution and stability. The optimized formulation was scaled-up and repeated, in order to evaluate reproducibility and feasibility of industrialization.3,The freeze-drying study of vinpocetine submicroemulsion: Lyophilization method was adopted to turn the vinpocetine submicroemulsion into lyophilized emulsion. The formulation and the preparative technique of the lyophilized emulsion were investigated by studying the influences of the types and concentrations of the cryoprotectants, as well as the prefreezing temperature and rates on the relevant characteristics of the lyophilized emulsion. The result showed that the maltose was the best. During prefreezing process, the temperature and rates had vital influence on the quality of the lyophilized vinpocetine emulsion. Fast prefreezing with -45℃generated nice effects for minor change happened to the particle size of the reconstituted lyophilized emulsion.4,The sterilization study of vinpocetine submicroemulsion: Different sterilizaition methods (moist heat sterillization, 60Co radiation sterilization and filtration sterilization) on submicron emulsion effect were investigated in this paper. The results indicated that radiation sterilization resulted in color change of sample appearance, filtration sterilization spent time due to strong force of resistance which might make the structure of submicron and made the sample unstability, and moist heat sterillization had no effect on appearance and related substance. In addition, moist heat sterillization method is simple and convenient. Furthermore, studying on pH regulating program suggested that pH of submicron emulsion should be regulated after moist heat sterillizating. After comprehensive sterilizaition methods research, moist heat sterillization under 121℃and 15 min conditions were selected as the final sterilization program.5,The stability study of vinpocetine submicroemulsion: Extreme condition, such as high temperature and light. The results showed that high temperature(60℃) and light would lead the drug content and increase the degradation products. In addition, the results of physical stability of vinpocetine submicroemulsion in different dilutions showed that the particle size in them didn't increase significantly within 24h.The vinpocetine submicroemulsion under 40℃for 3 months is stabile.6,Preliminary safety evaluation of vinpocetine submicroemulsion: The safety of vinpocetine submicroemulsion was evaluated by abnormally toxic test and hemolysis test (common test tube method in vitro).The results showed that vinpocetine submicroemulsion had neither serious intravenous toxicity nor hemolysis in the test tube method in vitro.Conclusion: The preparation technique was stable and repeatable. The results demonstrated that the tability of vinpocetine submicroemulsion of dilution and storage were fine. The result of the preliminary safety evaluation of vinpocetine submicroemulsion was fine.