| In the past 2 decades, microemulsion has been extensively used in transdermal drug delivery system due to many advantages including the thermodynamic stability, high solubility, rapid absorption and so on. It is very interesting to study drug-loaded microemulsion with special release properties of drug. In this study, podophyllotoxin microemulsion and microemulsion-based hydrogel were investigated with the support of Hubei Province Key Technology R&D Program"Research of Podophyllotoxin-loaded Microemulsion-based hydrogel"(2005AA301B10). The main findings are as follows:1. The stability of podophyllotoxin was studied by the RP-HPLC analysis method. The results showed that podophyllotoxin had a strong stability but it had a poor stability in solution, in which the ester group of podophyllotoxin would be controlled nucleophilic substitution reactions. The accelerated test showed that the contents of impurity were 18% in methanol and 4% in ethanol in 10 days. The pH values ranging from 3.5 to 3.9 would be advantageous to the stability of podophyllotoxin.2. According to the pseudo-ternary phase diagrams, microemulsion formulations were designed, and the capability of these microemulsions to improve the podophyllotoxin solubility and the stability of podophyllotoxin were studied. The results showed that microemulsion could effectively improve the solubility. The solubilization of podophyllotoxin in microemulsions was relative with the composition and structure of the microemulsions. Additionally, the stability study showed that the interfacial film comprised of Tween 80 and PG would parcel podophyllotoxin inside oily phase, which provide a good protection effect.3. The microemulsion-based hydrogels containing 0.5% podophyllotoxin for transdermal drug delivery were prepared using carbomer 940 as thickening agent of microemulsions. The influence of carbomer 940 on the structure of microemulsion, permeation rate and stability of podophyllotoxin was investigated. The results showed that the gelation didn't affect the structure of microemulsion and the microemulsion-based hydrogels still had good permeation ability, which followed the Fick's first diffusion law. The confocal laser scanning microscopy (CLSM) showed that podophyllotoxin from the microemulsion-based hydrogel could target skin when compared with tincture. The impact factors experiment showed that the increasing pH value of the system after gelation had adverse effect on the stability of podophyllotoxin.4. The novel microemulsion-based hydrogel (NMBH) consisting of Cremphor RH40, Comprotol 888, PG, water and cabmer 940 were prepared, and the properties of this NMBH including the formation of droplets in inner phase and permeation ability were studied. The results showed that the cooling temperature of this system could lead to various diameters of these microemulsions, and permeation rate could be further influenced. The targeting efficiencies (te) of the NMBH obtained at -76℃and -15℃were 1.32 and 1.03, respectively. It would seem that the NMBH had a certain feature of skin targeting effect of drug.
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