Studies Of Ethinyl Estradiol Transdermal Therapeutic System

Ethinyl estradiol is a synthetic steroid estrogen and is more potent than estradiol because the ethinyl substitution in the C17position. Ethinyl estradiol has been used by women for contraception, Hormone Replacement Therapy(HRT) or prevention of osteoporosis. The dosage forms of ethinyl estradiol available on the market are oral tablet subcutaneouly implant. However, at present, marketed transdermal therapeutic patches was not found.During the preformulation study,some physicochemical properties were studied. It has a low molecular weight,a low melting point, a higher octanol/water partition coefficient and low dosages of oral tablets.So it is a ideal medica for transdermal therapeutic systems.During the formulation study, the effects of various kinds of enhancers were investigated by a drug penetration test using excised guineapig back skin.Oleic acid and azone have the significant enhancement. Oleic acid is seleced as the enhancer in formulation because it is no sensitive to concentration.The effects of factors(type of polyacrylic acid,content of EE,enhancer) to adhensiveness and permeation of EE through guineapig back skin were studied by single factor experiment. In order to obtain the optimal drug delivery, the main ingredients, pressure sensitive adhesives (PSA) and permeation enhancers were chosen through orthogonal tests. Finally, based on the extensive development studies, a prototype of EE-TTS is prepared with8%E100,10%Oleic acid,6%-9%EE and mylar films.The method of HPLC has been developed to determine the content and relative substances of EE-TTS. Quality specification was established:sample size and shape, homogeneity, detection of relative substances, release rates, penatration rates and adhesiveness.The results above studies indicate thatEE-TTS is capable of7days continuous delivery of EE with a stable permeation rate. So it is a safe and effective transdermal therapeutic system.