沙格列汀二甲双胍缓释片的剂量倾泻风险评估

Assessing Risk of Alcohol-induced Dose Dumping for Saxagliptin and Metformin Hydrochloride Sustained-release Tablets

为探讨沙格列汀二甲双胍缓释片与含乙醇饮料同服而引起的剂量倾泻风险,本试验采用在0.1 mol/L盐酸介质中添加不同浓度乙醇(5%、20%和40%)的方法模拟药物与含乙醇饮料同服的情况,考察了自制和市售沙格列汀二甲双胍缓释片(Kombiglyze■XR)中盐酸二甲双胍的释放行为;同时考察了释放过程中不同转速(100、150和200 r/min)影响。结果表明,自制制剂中盐酸二甲双胍的释放略高于市售制剂;乙醇浓度升高时,盐酸二甲双胍的释放呈下降趋势;转速对盐酸二甲双胍体外的释放度影响不大,该自制处方发生剂量倾泻的风险可控。

The risk of dose dumping for saxagliptin and metformin hydrochloride sustained-release tablets induced by drinks containing ethanol was assessed. In this paper, 0.1 mol/L hydrochloric acid containing different concentrations of ethanol(5%, 20%, 40%) was adopted to simulate the situation of co-administration of drugs and ethanolic drinks, and the release behaviors of metformin hydrochloride from the self-made tablets and commercial tablets(Kombiglyze■ XR) were investigated. In addition, the effect of rotation speed(100, 150 and 200 r/min) during the release test was tested. The results showed that the release behavior of metformin hydrochloride from the self-made tablets were slightly higher than that of commercial tablets. With the increasing of ethanol concentration in release medium, the cumulative release of metformin hydrochloride showed a downward trend. And rotation speed had no significant effects on the release of metformin in vitro. It was concluded that the risk of alcohol-induced dose dumping in self-made formulation could be controlled.