Based on the Chinese Pharmacopeia specification of residual solvents in amoxicillin drug substance,the experiments were designed and conducted to evaluate the influence factors on residual solvents, including different type of stirring paddles, ammonia water adding speed, drying pattern, etc.The results showed that adding ammonia water with varying speed in different phases using paddle agitator, and drying with ammonia gas back flushing in electro- thermostatic blast oven can the solvent residue in amoxicillin could be reduced and the product quality could be improved to meet the requirements in different countries.