Studies Of Buprenorphine Transdermal Therapeutic System

Buprenorphine is a partial agonist atμ-opioid receptors but has also antagonistic or agonistic properties atκ-andδ-opioid receptors. It has long been in clinical use for treatment of moderate-to-severe pain. More recently, evidence has accumulated in support of its efficacy for maintenance treatment of heroin dependence, and the drug has been approved for this indication in numerous countries, including the United States, Australia, Sweden, and France. The dosage forms of buprenorphine available on the market are tablet, injection and capsule. However, at present, marketed transdermal therapeutic patches was not found.Buprenorphine has a strong pharmaco dynamic effect and a low molecular weight (504.11) and a suitable octanol/water partition coefficient, which causes it adaptable 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 buprenorphine with 3 kinds of penetration enhancers used alone were studied. For the successful development, a series of systematic studies were conducted. The prescription of buprenorphine 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 enhancer 1 can make a remarked synergistic enhancement of buprenorphine permeating through Guinea pig skin. Finally, based on the extensive development studies, a prototype of buprenorphine TTS is prepared with 10% buprenorphine, x% enhancer 1, y% enhancer 2, z% enhancer 3, 70% crylic acid PSA, and Polyester films.In this study, the effects of current density of alternating current, drug concentration, the enhancing effect of propylene glycol and on/off ratio on the in vitro skin permeability of buprenorphine have also been investigated. The result indicated that iontophoresis could modify the skin morphology and consequently, increase the passive transport of BUP at a certain current density, drug concentration, on/off ratio, which are 0.3 mA/cm~2, 0.3mg/mL and 1:2 respectively. Besides, when buprenorphine was transported iontophoretically, passive skin pretreatment with 1% propylene glycol, produced higher flux values than iontophoretic skin pretreatment.The method of UV was used as distinguished. The method of HPLC has been developed to determine the content and relative substances of buprenorphine TTS.Quality measures included sample size and shape, homogeneity, detection of relative substances, release rates, penatration rates and adhesiveness.The results above indicate that buprenorphine -TTS is capable of 1 days continuous delivery of buprenorphine with a stable permeation rate and has not any skin irritation. So it is a safe and effective transdermal therapeutic system.