Abstract: OBJECTIVE To optimize the production technology of amlodipine besylate tablets using lactose as the excipient, and meet the requirements of Chinese pharmacopoeia 2015 edition for the control of the related substances in amlodipine besylate tablets. METHODS It was optimized that the technology of powder direct compression by orthogonal tests. At the same time, the accelerated test for the products about optimized and previous technology was carried out, in order to compare the related substances and dissolution in the products. RESULTS The optimum process was as follows: amlodipine besylate was milled to the particles through a 100-mesh screen, mixing the particles with microcrystalline cellulose, granulating and coating the granules with 2% HPMC, drying, mixing with other excipients in the original formulation, tableting. During the study period, the related substances in the amlodipine besylate tablets of optimized technology were significantly lower than that of the previous technology, and the dissolution was in accordance with the provisions of the Chinese Pharmacopoeia 2015 edition. CONCLUSION This new concept may be provided for the preparation of the amlodipine besylate tablets using lactose as excipient.