| Ethinyl estradiol (EE) is a kind of orally effective estrogen. It is not only used for additional of estrogen, but also used for the alleviative treatment of carcinoma of prostate in clinic. There are only oral tablet and subcutaneouly implant preparation in domestic market at present. This drug has low bioavailability, adverse reaction of gastrointestinal tract by oral administration, and is administered frequency. For elevating the compliance of patient's medication and decreasing the adverse reaction, this article carried out the study of transdermal preparation of EE. The main four parts of this study are: (1) the preformulation study for the development of transdermal preparation of EE;(2) screening the formulation of patch using various kind of acrylic resin as pressure-sensitive-adhesive (PSA), carrying out the in vitro, in vivo, and the quality standard study of patch;(3) investigation of ethosome and liposome, transfersome, proniosome lipid vesicles as drug carriers on percutaneous permeation of EE;(4) using the Carbopol 934 as gel material, carrying out the transdermal study of EE alcohol gel.In the preformulation study, the HPLC method for the assay of EE was established firstly and the solubility in various solvent systems such as alcohol, propylene glycol, PEG400 was examined. Then the influences of solvent and penetration enhancer (alcohol, propylene glycol, oleic acid, isopropyl myristate, azone) on the percutaneous permeation of EE were studied. The results showed that EE had a high liposolubility and its water solubility was only 55.2μg/ml, which belonged to insolubility drug. Alcohol and propylene glycol of different concentration could increase the solubility of EE. Ethanol exhibited well promotion in vitro percutaneous study of EE, and with the increase of the ethanol concentratin, the enhance ration first increased and then decreased. 30% ethanol showed the best promotion in vitro percutaneous study of EE. Oleic acid and isopropyl myristate could increase the flux with the former having the better effect. Azone inhibited the percutaneous permeationofEE.In the EE patch study, a monolithic drug-in-adhesive transdermal patch was developed using acrylic resin as PSA matrix. The result of screening formulation showed peneteation enhancer A exhibited well promotion in vitro percutaneous study of EE. Combing the Eudragit El 00 and Eudragit RS 100 as PSA, the patch we got had a bad physical character. The patch using domestic acrylic resin as PSA matrix had good physical character, but low flux. The best patch we got had good physical character and the flux reached 0.50±0.02μg/cm2/h, and the accumulative penetration amount of 20cm2 in 24hr reached 240±7^g. The bioavailability of this patch was higher than oral administration through rabbit in vivo experiment. According estimation, the penetration could reach the clinical requirement. A method for the assay of EE in patch was established. EE and acid, base, oxide degradation product could assayed using this method. The result of stability study showed that the patch was stable to hot and moist, unstable to light. The content and physical character of patch had no marked change, which placed under common temperature for three months.In the colloidal carrier study, using ethosome as drug carriers on percutaneous permeation, EE ethosome was prepared. The influence of alcohol kind and concentration on encapsulation, percutaneous penetration parameters of EE ethosome in vitro and the EE retention amount in the skin were stusied. Liposome, transfersome and proniosome of EE were prepared and theirs percutaneous penetration in vitro were studied. The result revealed that ethosome promoted the percutaneous penetration of EE and increased the EE retention amount in the skin significantly. The highest flux of EE through human cadaver skin from ethosomes reached 4.85 + 0.47μ^cm2;'!!, which the enhance ratio reached 13.5 vs saturated aqueous solution of EE. Ethosomes is a new, safe and effective EE carrier on percutaneous permeation and the preparation is simple. Liposome, transfersome and proniosome all could increase the flux of EE, in which proniosome had the best effect. But theirs penetration enhance effect were poor than ethosomes.In the alcohol gel study, EE gel was prepared using the Carbopol 934 as gel material. The influence of alcohol kind and concentration on percutaneous penetrationparameters in vitro and the EE retention amount in the skin were stusied. The result revealed that alcohol gel promoted the percutaneous penetration significantly. The highest flux of gel reached 6.78±0.5(^g/cm2/h and the enhance ratio reached 18.8 vs saturated aqueous solution of EE. The enhance effect showed para-curve with the ethanol concentration. The addition of propylene glycol decreased the flux. Ethosomes were incorporated in carbopol gel, and then we got ethosomal gel. Ethosomal gel not only increased the flux of EE significantly, but also increased the EE retention amount in the skin. Ethosomal gel was a promising transdermal preparation of EE.This study prepared the EE patch, ethosome, ethosomal gel, and gel four preparations successfully. They all reached the higher flux, which could meet the clinical requirement. The bioavailability of EE patch was higher than oral administration through rabbit in vivo experiment. Ethosome and ethosomal gel not only increased the flux of EE significantly, but also increased the EE retention amount in the skin. The study of EE transdermal delivery has not been reported in domestic and abroad. This study established the foundation for the new administration and new preparation of EE.
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