Studies Of Levonorgestrel Transdermal Therapeutic System

Levonorgestrel is a very pouplar oral prophylactic in the world. In nowadays, the prophylactic is single or compound of levonorgestrel in the markets, and the dosage forms of it available on the market are tablet, dripping pills and implant. However, at present, marketed transdermal therapeutic patches was not found.Levonorgestrel has a strong pharmaco dynamic effect (contraceptive dose is 20～25μg/d). It has a compatible molecular weight (312．45) and a surely octanol/water partition coefficient (logPo/w = 3．48) .So it is adapted to be made as transdermal therapeutic systems (TTS).In this thesis, some physicochemical properties and the transdermal delivery across Guinea pig skin in vitro of levonorgestrel with 3 kinds of penetration enhancers used alone were studied. For the successful development, a series of systematic studies were conducted. The prescription of levonorgestrel TTS were designed. Pharmaceutical analysis methodology, quality standard and the properties of preparations were studied.In order to obtain the optimal drug delivery, the main ingredients, pressure sensitive adhesives (PSA) and permeation enhancers were chosen through orthogonal tests. The results show crylic acid PSA and single permeation enhancers of IPM can make a remarked synergistic enhancement of levonorgestrel permeating through Guinea pig skin. Finally, based on the extensive development studies, a prototype of levonorgestrel TTS is prepared with 3% levonorgestrel, 5% IPM, 15% RS100, 60% crylic acid PSA, and mylar films.The method of UV was used as distinguished. The method of HPLC has been developed to determine the content and relative substances of levonorgestrel TTS.Quality measures included sample size and shape, homogeneity, detection of relative substances, release rates, penatration rates and adhesiveness.The results above studies indicate that levonorgestrel-TTS is capable of 3 days continuous delivery of Ievonorgestrel with a stable permeation rate and has not any skin irritation. So it is a safe and effective transdermal therapeutic system.