Research On Preparation Technology Of Compound Amlodipine Besylate And Atorvastatin Calcium Double-layer Tablets

Hypertension patients complicated with hyperlipidemia increases the risk ofcardiovascular disease.If not controlled early, it will promote the development ofatherosclerosis. The coronary heart disease (CHD) is one of the main causes of death inthe world’s population. This view has been the consensus of the community.At high riskof disease of Cardiovascular disease pass reach, is currently the only effectiveprevention and treatment methods.Atorvastatin calcium and Amlodipine besylate tabletsis used for the treatment of hypertension complicated with hyperlipidemia Compoundpreparation, which is the first preparation contains two active ingredients for differentsymptoms. Both drugs in their areas of treatment with high clinical share sales andgreat market. There is an obvious incompatibility between Atorvastatin calcium andAmlodipine besylate, and the pH micro-environment which the two drugs requirementis inconsistent. So in order to solve these incompatibility issues, the compoundpreparations designed to be double-layer tablets.According to the different solubility and stability of the two drugs, the prescriptionand the preparation process of two pieces of layer respectively were studied. The studyon the method of single factor experiment and orthogonal experiment. According to theresults of dissolution and stability test, finally determined the priscription and thepreparation process. at the same time， Study on reproducibility of the productionprocess.Atorvastatin calcium tablets layer adopts dry granulation technology in process,its prescription is: microcrystalline cellulose44%, Pregelatinized starch17%,cross-linked polyvinylpyrrolidone9%, calcium carbonate9%, talcum powder0.5%,magnesium stearate0.5%. Amlodipine tablets layer adopts direct powder compressionechnology in process, its prescription is: Microcrystalline cellulose44%, dicalciumphosphate35%, sodium carboxymethyl starch5%, talcum powder0.5%, magnesiumstearate0.5%.Through the study of prescription，Use dry granulation tabletting process tosolvethe Atorvastatin Calcium Tablets layer‘s solubility stability problem. The keyprocess parameters: dry granulating machine extrusion speed15rpm, feed speed12rpm,the extrusion pressure18Kg. In the Amlodipine Besylate Tablets layer,use theimproved technology of direct powder compression technique to replaced the method ofwet granulation.The Technology be proved much more suitable for Amlodipine besylate,and Improved the quality of the products. The key process parameters: the mixed timeis10minutes. After the pilot study show that the process has good stability,reproducibility. The research of the preliminary stability proved that the product qualitystability is good.