Studies On Rivastigmine Transdermal Patchs

Rivastigmine(RVT), a cholinesterase inhibitor, is available for the treatment of mild to moderate Alzheimer’s disease. It is widely used in clinic both in China and other nations. Rivastigmine is currently approved by FDA in three formulations(capsules, solutions, and transdermal patches), but in China only capsules was approved. Novartis’ s rivastigmine patch is the first non-oral drug treatment for dementia of Alzheimer’s disease. The patch is currently available in the United States, Japan, the European Union approved the trade-name Exelon?.Exelon patch is usually taken once daily, easy to use; through the skin allowing a smooth, sustained release remainder of the 24-hour period of application, to maintain a stable blood concentration. The patch causes no gastrointestinal absorption, thus the gastrointestinal adverse reactions are greatly reduced. Exelon patch has a very broad market prospects.The main contents of this paper are:(1)Establishing an assay method for assay, related substances, skin permeation in vitro and release;(2)Formulation and manufacture of rivastigmine transdermal patch;(3)The sample and the original product conformance assessment;(4) Comparative study of the sample and original product in animals preliminarypharmacokinetic behavior.This paper established a method used for determine rivastigmine transdermal patch assay, related substances, skin permeation in vitro and release, such evaluation methodology may laid a foundation for formulation and manufacture research.In this paper, we conducted extensive studies on the possible impact on product quality prescription process factors, such as pressure-sensitive type and amount, the amount of thickener, adhesive layer coating thickness, glue preparation, initially identified the prescription formulation. Through the continuous preparation of three batches of pilot samples, the prescription process validation results show that the formulation process good reproducibility, which is suitable for industrial scale-up. And the product quality is stable and controllable.In this paper, we conducted comprehensive quality studies on three batches of the patch, including characteristics, pH, adhesion, related substances, release, skin permeation in vitro, assay, content uniformity, as well as stability. The results showed that the sample had developed quality consistency compared with the original product.This paper established the LC-MS/MS method to assay rivastigmine plasma drug concentrations. Using parallel trial design, New Zealand white rabbits were given the sample and the original product separately to assay plasma concentration, and DAS2.1.1 software was used to calculate thepharmacokinetic parameters such as AUC, t1/2, tmax, and cmax. The results showed that the pharmacokinetic parameters between the sample and the original product has no significant differences, which indicated the sample and the original product had similar pharmacokinetic characteristics. In this paper, we conducted studies of skin irritation, the results showed that the sample were no skin irritation.