A Study Of Rivastigmine Transdermal Drug Delivery System

Rivastigmine is a novel acetylcholinesterase(AChE) inhibitor, displaying specificity for central AChE over peripheral AChE. It is very popular to use in Alzheimer's disease therapy. At present, the dosage forms of rivastigmine are mainly tablets and capsules. Only Novartis has a patent of rivastigmine transdermal drug delivery system(TDDS). However, there is not any marketed rivastigmine transdermal patch in China. The prescription of rivastigmine TDDS were designed. And a HPLC method for the determination of rivastigmine in patch and its skin permeation behavior in vitro was established. At the same time, a quality standard of rivastigmine TDDS was made.1. In order to get the optimal rivastigmine TDDS, the main ingredients, permeation enhancers and pressure sensitive adhesives (PSA) were chosen according the tests'results. Based on the development studies, the rivastigmine TDDS was consisted of 9 mg/5 cm2 rivastigmine, 2% A as the single permeation enhancer and PSA:RS100=5:1.2. A HPLC method for the determination of rivastigmine in patch and its skin permeation behavior in vitro was established. The linear ranges of HPLC was 5.09μg/mL-101.70μg/mL (r=0.9999) with LOD of 0.17μg/mL. The RSDs were 0.12%-0.47%. The mean recoveries of low, middle and high concentrations of rivastigmine were 98.79%,98.59%,99.88%, respectively. The method was simple, rapid, sensitive and accurate. It can be used to determine rivastigmine in TDDS.3. A quality standard of TDDS includes sample size and shape, evenness, detection of relative substances and release rates. The results showed the qualities of rivastigmine patches met the requirements of pharmacopoeia. The content of relative substances was less than 1%. During 24 hours, the cumulative release quantity of rivastigmine was more than 90%.4. The kinetic penetration equation of KBD's patches was Q= 62.88t+ 35.56, R= 0.9927. And the kinetic penetration equation of control group was Q= 61.58t+21.83, R= 0.9945. The two kinds of rivastigmine patches had the similar percutaneous permeability.