Studies On Capsaicin Topical Microemulsion

In this dissertation capsaicin as a model medicine was prepared into microemulsion with surfactant and without surfactant, which is the exploratory investigation of capsaicin microemulsion.The high performance liquid chromatography was used to assay the content of capsaicin and the method authentication showed the linearity is between 4.93～148.0μg/mL. The precision and accuracy meet the requirement of this experiment. During the preformulation study the solubility in different solvents was determined and the oil-in-water partition coefficient was assayed in various pH value solutions. The research on various permeation membranes showed the viable epidermis is one of the rate limiting layer in the full skin. Various types of penetration enhancers were studied and the results showed camphor is the effective enhancers to capsaicin.Phase diagrams were used to determine the region of microemulsions. In the systems with benzyl alcohol, the influence of hydrophile-lipophile balance and the type of surfactant and cosurfactant on phase diagrams was reseached. The effects of surfactant and cosurfactant on the surface tension were studied too. Benzyl alcohol-1,2-propylene glycol-water system was selected as microemusion free of surfactant. Then the effects of oil phase, cosurfactant and water on the permeation rate were studied. The results showed the transdermal permeation rate increase with the increasement of the content of benzyl alcohol and water in specific region. Simplex lattice design was introduced to optimize the formulation of microemulsion, and benzyl alcohol 29.3%, 1,2-propylene glycol 27.4% and water 43.3% is the optimal formulation. The small angle X ray diffraction and fourier transformation infrared spectrum were applied to represent the effects of microemulsion on the stratum corneum. The results showed the crystals in the stratum corneum were disintegrated to amorphous state under the effect of microemusion. The microemulsions were characterized by dynamic laser scattering system and electronic scanner microscope. The particles size is about 6.6~16.6 nm and the shape is sphere.The conductivity, viscosity and distribution of particle size were also determined. The physical stability was studied by centrifugation, which showed the microemulsion was stable.After multiapplication in mice and single dose in human, the irritation of capsaicin microemulsion showed there is no obvious influence on the mice skin tissues, and the subjects feeling and color analysis represented shorter onset time and stronger efficacy of microemulsion than that of ointment. Confocal laser scanning microscopy confirmed microemulsion can enhance fluorescent pink to permeat into deep layer, which showed the good performance of permeation enhancement.The in vivo samples were assayed by HPLC-fluorescence detector and the linearity is between 0.197～49.3μg/mL and the detecting limit is 5.9 ng/mL. The precision and accuracy meet the requirement of this experiment.The in vivo pharmacokinetic in rabit showed the half-life of capsaicin in microemulsion and alcohol is 10.89 min and 9.53 min respectively, which confirmed the microemulsion does not affect the metabolism of capsaicin in rabits. This represents the practicability and scientificalness of this project.