Design And Evaluation Of Vinpocetine Transdermal Delivery System

Improving the transdermal permeability of poorly water-soluble vinpocetine (VIN) was considered as main focus of this paper. The pressure sensitive adhesive (PSA) patch and microemulsion system were prepared, respectively. Combing the cytobiology experiment, physical enhancing method and in vivo pharmacokinetic experiment of minipig synthetically, the in vitro/in vivo transderml permeation kinetic behavior of VIN and the relevant mechanism were deeply studied.During the preformulation study, the drug solubility, oil/water partition coefficient and melting point were determined. According to the value of partition coefficient, permeation coefficient and diffusion coefficient, the main transdermal route of VIN was proved to be the inter-cell lipid of the epidermis and the barrier was stratum corneum. In the in vitro permeation experiment, 30% ethanol-water was chosen as receptor medium to maintain the sink condition. Different permeation enhancers were selected to improve the permeation of VIN and the enhancing mechnism was considered to be the interaction with the groups in the inter-cell lipid by the calculation of partition coefficient, permeation coefficient and diffusion coefficient and the identification of lipid membrane model.Basing on the result of preformulation, Eudragit IV, Eudragit E100, Gelva 737 and BIO -PSA4201 were chosen as candidate PSA to invetigate their effects on the sustained adhesion and accumulative permeation amount of VIN. The solubility index was obtained from DSC analysis to predict the thermoactivity and permeation competent of VIN and linear relationship was found between the permeation amount and solubility index (r>0.9) . Eudragit E100 was chosen as suitable PSA and the content of the plasticizer and cross-linker were studied to evaluate the effects on the tackness and sustained adhesion of patch by contour method. 26 enhancers were included in the formulation of PSA patch and the relationship between their structure and enhancing ability were represented. Linoleic acid was outstanding due to the highest enhancing ratio and the PG was followed as coenhancer. 5% PVP was determined as an important addictive to avoid the crystal precipitation.The spherical symmetric design was applied to optimize the formulation of PSA patch, with the content of plasticizer, enhancer and PG as three factors, bootstrapt standard error evaluation, sequential quadratic programming model and gradient method as statistical means. The statistical parameters and matrix scatter plot showed that predicted value by second-order regression equation was highly similar to experimental data. The optimized formulation was obtained by SOLVER tool and the two-layered patch was prepared to maintain the dynamic power after 12h.A novel microemulsion was prepared to increase the solubility and the in vitro transdermal delivery of VIN. For the microemulsions, oleic acid was chosen as oil phase, PEG-8 glyceryl caprylate/caprate (Labrasol ) and Cremophor EL as surfactants (S), purified diethylene glycol monoethyl ether (Transcutol P) as cosurfactant(CoS) and the double-distilled water as water phase. Pseudo-ternary phase diagrams were constructed to obtain the concentration range of each component for the microemulsion formation. The effects of various oils and different weight ratios of surfactant to cosurfactant (S/CoS) on the solubility and permeation rate of vinpocetine were investigated. The effect of different addictives on the PIT was also investigated.Self-diffusion coefficients were determined by PFG-NMR in order to investigate the influence of microemulsion composition with the equal drug concentration on their transdermal delivery. The linear correlation between transdermal permeation rate and structural characteristics of vinpocetine microemulsion was investigated. The physicochemical properties of the optimized microemulsion were examined for the pH, viscosity, refractive index, conductivity and particle size distribution. The effects of various content of microemulsion composition on physicochem...