口服固体制剂中泛昔洛韦与乳糖的美拉德反应研究

Study on Maillard Reaction Between Famciclovir and Lactose in Oral Solid Dosage Forms

关键词:  口服固体制剂  泛昔洛韦  乳糖  美拉德反应  差示扫描量热法  高效液相色谱法  液相色谱-质谱联用法

Key words:  oral solid dosage  famciclovir  lactose  Maillard reaction  differential scanning calorimetry  HPLC  LC-MS

摘要:

目的 考察泛昔洛韦与乳糖在口服固体制剂中产生美拉德反应的条件,建立美拉德反应产物(Maillard reaction productions,MRPs)的监测方法,指导制剂开发。方法 参照美拉德反应机制和固体制剂生产工艺,选择水分、温度和时间作为主要研究条件,采用目视法和差示扫描量热法对美拉德反应进行初步评价;采用HPLC和LC-MS对MRPs进行鉴别和质控。结果 在水分 ≤ 10%、温度 ≤ 90℃时,泛昔洛韦与乳糖相容性良好,且不产生美拉德反应;并可采用HPLC对MRPs进行质控。结论 泛昔洛韦在口服固体制剂处方工艺开发与乳糖联用时,应进行水分和温度的控制,降低产生美拉德反应的风险。

Abstract:

OBJECTIVE To investigate the Maillard reaction conditions between famciclovir and lactose in oral solid dosage and to establish methods of monitoring Maillard reaction productions(MRPs), to guide formulation development. METHODS According to the Maillard reaction mechanism and the manufacture process of the solid dosage form, selected water, temperature and time as the main research conditions, used visual inspection and differential scanning calorimetry to conduct preliminary evaluation of the Maillard reaction, used HPLC and LC-MS to identify and control MRPs. RESULTS When the water ≤ 10% and the temperature ≤ 90℃, famciclovir was good at compatibility with lactose and did not cause the Maillard reaction, the method of HPLC could be used for quality control of MRPs. CONCLUSION When famciclovir combined with lactose in the development of oral solid dosage forms, water and temperature should be controlled for reducing the risk of producing Maillard reaction.