The Study Of Vinpocetine In Situ Forming Gel And Microparticles

Using new technologies and biodegradable polymers to develop microshperes, nanoparticles and gel is one of the most promising area in pharmacy. Vinpocetine is a kind of effective drug for cerebrovascular disease. However, it is almost aqueous insoluble, which significantly restricts its bioavailability to 7%. In this paper, vinpocetine was used as the model drug to prepare in situ forming gel and microparticles, with the aim to prolong its action time, reduce the times of administration and enhance the bioavailability.In this paper, the HPLC method, which was suitable to detect vinpocetine in formulations, was firstly established. By single factor tests, the optimal formula of in situ forming gel was obtained. Because there were quite a few factors influencing the in situ forming microparticles, the spherical symmetric design-response surface methodology was utilized to optimize the formulation.The study on the drug release mechanism showed that the the releasing process was fitted to diffusion, or the synergism of diffusion and bulk erosion. The stability test indicated that both the in situ forming gel and microparticles were stable when exposed to high temperature, high humidity and light. The accelerated test showed that both the formulations were rather stable after package.The pharmacokinetics study on the prepared vinpocetine in situ forming gel, microparticles and BB solution was carried out with rabbits. The analytical procedure was based on HPLC method. The results revealed that the T_max,C_max and AUC_0-t of in situ gel, in situ microparticles and BB solution were 2h, 410.5±76.8 ng·ml^-1, 618.4±96.5 ng·d·ml^-1; 3h, 2121.6±121.3 ng·ml^-1, 813.6±71.6 ng·d·ml^-1; 1h, 2757.1±172.9 ng·ml^-1, 486.5±47.5 ng·d·ml^-1 respectively. Using vinpocetine BB solution as the reference, the bioavailability of the vinpocetine in situ forming gel and microparticles were 17.6% and 24.8%, respectively. Calculated with Loo-Riegelman method, the in vitro-in vivo correlation of vinpocetine in situ forming gel was significant(df=23, 0.597<r_1-0.001/2 <0.652). Based on the vinpocetine plasma concentration as the weight function, the in vitro-in vivo correlation of in situ forming microparticles was significant calculated with convolution(df=30, r_1-0.001/2=0.554).