| Scutellarin, a bioactive component of flavonoid glycoside, is adopted for the treatment of apoplexy sequel, coronary artery disease and angina pectoris in clinic, which is a potent medicine for the treatment of heart vascular disease in aged people. However, scutellarin exhibits short biological half-life, quick elimination and low oral bioavailability, which restrict its application in clinic. The transdermal delivery system could overcome the disadvantage of these traditional dosage forms.This paper is focused on the transdermal delivery formulation of scutellarin, aiming at increasing the percutaneous permeation abilities. The content is as follows:1.The method for determination of the content of scutellarin in the in vitro release experiment and the in vitro transdermal percutaneous experiment was constructed. The linear relationship was good, the precision was high, and the accuracy was well, which made the results accurate and reliable.2. The solubilities and the stabilities of scutellarin in water, short-chain alcohol and PBS solution in different pH was investigated. The PBS solution (pH=7.0) was determined as the solvent during the the preparation of the scutellarin ethosomes.3. The percutaneous abilities and the metabolic characteristics of the scutellarin ethosomes were studied. scutellarein, the percutaneous metabolite of scutellarin, was identified by HPLC/MS, which possessed the same pharmacological activities as scutellarin. The in vitro percutaneous abilities and the metabolic characteristics of scutellarin+PBS+ethanol (Scu-PBS-E), scutellarin+blank ethosomes (Scu-BES), scutellarin ethosomes (Scu-ES), scutellarin ethosomes+5% azone+1% tween-80 (Scu-ES-A-T) were compared, and the results indicated that the percutaneous ability of scutellarin was increased when the ethosomes was adopted as the trasdermal delivery system of scutellarin, and the penetration enhancers could improve the percutaneous ability of scutellarin ethosomes.4. Base on the single-factor investigation, the formulation of scutellarin ethosomes was optimized by orthogonal design, in which the parameter of the in vitro percutaneous kinetics were set as the index, the average droplet size, polydispersity, the encapsulated ratio, and zeta potential were also investigated in the study. The results indicated that, phospholipid, ethanol, and the drug content were significant factor. The optimized formulation contained 1% phospholipid,45% ethanol, and 0.35% drug content. The average droplet size of scutellarin ethosomes was 104 nm. The scutellarin ethosomes had narrow size distribution. The zeta potential was -2.25mV, and the encapsulated ratio was 19.17%±3.63%.5. The influence of the common used penetration enhancers on the the percutaneous ability of scutellarin ethosomes was studied, and the results showed that,5% azone exhibited better penetration enhancement, which could significantly increase the stable percutaneous flux and the cumulative amount of scutellarin in 24 h, however the lag time was much longer. When 5% azone was adopted together with 5%camphol, the disadvantage could be overcame.6. The preparation technology and the formulation composition of the scutellarin ethosomes were studied. The gel matrix materials were screened from formability, consistency, malleability and moisture retention. The in vitro percutaneous release of these formulation was conducted to obtain the optimized formulation, and 1% carbomer was selected as the final gel matrix.7. The quality evaluation of the scutellarin ethosomes gel was conducted from the physic-chemical properties, the content and uniformity of the gel. The uniformity was well in the batch (RSD=2.62%), and the content variance was also small between the batches (RSD=3.15%). The safety of the scutellarin ethosomes gel was evaluated, and the results showed that there's no irritation to the skin.
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