复方维A酸乳膏化学稳定性研究及有效期预测  

Chemical stability of compound tretinoin cream and prediction of its period of validity

作　　者：张志勤[1] 王栋[1] 邵丰德[1] 韩国柱[2] 唐泽耀[2] 

机构地区：[1]大连市皮肤病医院药剂科,大连116021 [2]大连医科大学药理教研室,大连116044

出　　处：《中国新药杂志》2015年第2期212-217,220,共7页Chinese Journal of New Drugs

摘　　要：目的:研究复方维A酸乳膏的化学稳定性并预测其有效期。方法:HPLC法同时测定复方维A酸乳膏中3组分(维A酸,尿囊素和维生素E)的含量及异构化产物异维A酸。对高湿、光照和热稳定性进行考察;从4个不同温度避光条件下不同时间测得的含量,求出各温度的反应速率常数;按Arrhenius方程求出25℃下的t0.9,从而预测其有效期。结果:该复方乳膏高湿条件下稳定,当其常温条件下暴露于4 500 Lx照度下光照5和10 d,其中维A酸含量分别下降至85%和70%左右,同时测得异维A酸含量相应上升。其他2种成分含量未见明显下降,单方维A酸乳膏在此条件下,降解显著。3种成分的受热降解符合一级动力学。该复方乳膏25℃避光条件下维A酸、维生素E和尿囊素的t0.9分别为370,476,482 d,单方维A酸的t0.9仅为253 d。根据加速试验预测40℃下放置1个月的降解与实测值吻合。正常条件下存放亦与预测相符。结论:3种成分中维A酸最不稳定,易见光异构化,对热则相对稳定;组成复方制剂后,维A酸化学稳定性较其单方大有提高,该复方乳膏的有效期在1年左右,应避光保存。Objective： To study the chemical stability of the compound tretinoin cream and predict its period of validity. Methods： HPLC method was used for determination of the three components in the compound cream and isomerization product isotretinoin. The high moisture,strong light,and thermal stability were investigated. The thermal stability was studied by thermostatic acceleration test. After obtaining rate constants at four different temperatures,the t0. 9（ 25 ℃） was calculated according to Arrhenius equation,and used to predict the period of validity of the cream. Results： The cream was very stable against high moisture. After exposure to light at 4 500 Lx for 5 d and 10 d,the tretinoin content was significantly lowered to 85% and 70% of the initial values,respectively,meanwhile the isotretinoin content was elevated. The thermal degredative reaction of the three components complied with the first order kinetics. Tretinoin,vit E,and allantoin in the compound cream were estimatred to have longer t0. 9（ 25 ℃） of 370 d,476 d and 482 d,respectively,compared with the 253 d for tretinoin cream. The practically measured content of tretinoin at 40 ℃ for 1 month and at 25 ℃ for 370 d corresponded to the predicted results. Conclusion： Compared with Vit E and allatoin,thetinoin is less stable. It is most sensitive to light,leading to isomerization,but is relatively stable against temperature,and becomes much more stable when formulated as compound cream than in mono-component cream. The period of validity of the compound cream is established as 1 year and it should be stored away from light.

关 键 词：复方维A酸乳膏 稳定性 有效期 HPLC 

分 类 号：R943.3[医药卫生—药剂学]