Formulation And Preparation Research Of Rivastigmine Transdermal Patch

Rivastigmine(RVS)is a cholinesterase inhibitor used to treat Alzheimer's disease(AD).Currently there are three formulations of RVS on the market,included capsules,oral liquids and patches.The usage and dosage of the patch(commercial name: Exelon patch)is once a day,which effectively reduced the frequency of administration and the side effects.Currently,it has not been approved in China.Therefore,it is meaningful to develope the RVS transdermal patch which are consistent with the Exelon patch for the AD patients in China.In this research,the Exelon patch produced by Novartis was regarded as the reference formulation.The drug stability,release degree,transdermal permeability,and adhesiveness were used as evaluation indexes to optimize the formulation and preparation process,and develop the RVS transdermal patches which are consistent with the Exelon patch.First,the pre-prescription research was tested the physicochemical properties and stability of RVS,and a forced degradation test was performed.The results showed that RVS has a suitable Log P for TDDS,the solubility of RVS in physiological saline can meet the condition of sinking,and the stability in 24 hours is suitable.Therefore,physiological saline is selected as the dissolution medium for in vitro release test and in vitro percutaneous penetration test.The factors of experiment showed that the stability of RVS under the conditions of high temperature,high light and high humidity was not good,and the forced degradation experiments showed that the drug was easily oxidized in H2O2.Then,the compatibility of different types of acrylate pressure-sensitive adhesives,acrylate resins and silicone pressure-sensitive adhesives with drugs was investigated through influence factors.Several excipients with good compatibility of RVS were used to screen drug-containing matrix by release experiments.Therefore,choose the 87-2051/Acrylic A,which is basically consistent with the release behavior of the reference preparation,was determined as the drug loading matrix.Adhesion layer is selected from silicone PSA A with strong cohesive force and good biocompatibility as the adhesive layer directly in contact with the skin.The stability of the test patch was determined by the influence factor.0.1% BHT was used as an antioxidant in the formulation.The adhesion test was used to determine the amount of simethicone in the adhesive layer to be 1.0%.After the formulation of RVS patch is confirmed,the preparation process was optimized and screened.The mixing process,coating process and drying process were investigated with the indexes of drug content,content uniformity,related substances and residual solvents as indicators.So the production process of RVS double-layer patch was confirmed.Finally,the quality of the three batches of samples verified by the prescription process was initially examined and compared with the Exelon patch.The results showed that the content uniformity,related substances,and adhesiveness of the self-made patches met the requirements of the pharmacopoeia,and the release degree,and skin residency was no significant difference between the self-made patches and the Exelon patch,the cumulative permeability in vitro was also similar.