Study on stability of levamlodipine besylate tablets

LI Jie; CHEN Wei; YANG Wen-wen; GUO Xing-hui

Abstract：Objective:To investigate the related substances and content of levamlodipine besylate tablets from 11 manufacturing enterprises in China after being placed for 5 d and 10 d in the light,high temperature and high humidity conditions,and study the correlation between the content of amlodipine lactose adduct under ambient temperature and humidity.Methods:The column was Agilent XDB C18 (250 mm × 4.6 mm,5 μm);the mobile phase was methanol-acetonitrile-0.7％ triethylamine [7.0 mL of triethylamine diluted with water to 1 000 mL,pH adjusted to (3.0-± 0.1) with phosphoric acid,Vmethanol∶ Vacetonitrile∶ Vtriethylamine =35∶15∶50];the detection wavelength was set at 238 nm;the flow rate was 1.0 mL·min-1;the column temperature was 30 ℃,and the injection was 20 μL.Results:Dehydro-amlodipine was detected in the products of all 11 enterprises.Lactose adducts were detected in the products of 3 manufactures using lactose or dextrin.Light and temperature had greater impact on the dehydrogenation of amlodipine and total impurities content,while temperature had greater impact on levamlodipine content.The amount of lactose adduct was positively correlated with the environment temperature,humidity and time of storage.Conclusion:Lactose adduct is generated when Maillard reaction takes place between lactose acid and the primary amino groups of levamlodipine with the catalysis of magnesium stearate.It was recommended that the manufacturers using lactose change the prescription and process,light be avoided during the production process,and temperature and humidity in the workshop be controlled.Drying temperature of the materials should not be too high if using wet granulation.Lighttight materials with good barrier action should be used for the packaging,and the products should be stored in a dark and cool place after being sealed.