Results of a study on the interaction between enalapril malete (EM) and excipient sodium starch glycolate (SSG)

Disintegrant sodium starch glycolate (SSG) shows a detrimental effect on the stability of the active pharmaceutical ingredient (API) enalapril malete (EM). EM presents two pathways for degradation that are dependent on the pH of a given solution: a cyclisation product diketopiperazine (DKP) is formed at a low pH and hydrolysis to enalaprilat (ET) occurs at a high pH. Mixing EM and SSG together results in degradation to DKP in the solid state. Since SSG is used as a disintegrant in formulations, we believe moisture and pH are the cause of the degradation of EM. Below presented are results of studying this effect. The majority of the results are composed of binary mixtures of EM and SSG where conditions as humidity, particle size, pH, moisture content and ratio of mixtures were varied.崩解剂羧甲淀粉钠（sodium starch glycolate, SSG）对药物活性成分（active pharmaceutical ingredient, API）马来酸依那普利（enalapril malete, EM）的稳定性具有不利影响。马来酸依那普利存在两条依赖于体系溶液pH值的降解途径：低pH条件下会生成环化产物二酮哌嗪（diketopiperazine, DKP），高pH条件下则会水解生成依那普利拉（enalaprilat, ET）。将马来酸依那普利与羧甲淀粉钠混合后，二者在固态下会发生降解生成二酮哌嗪。由于羧甲淀粉钠常被用作药物制剂中的崩解剂，我们推测水分与pH值是导致马来酸依那普利降解的关键因素。下文将呈现针对该效应的研究结果，多数实验数据来源于马来酸依那普利与羧甲淀粉钠的二元混合物体系，实验中调控了湿度、粒径、pH值、水分含量以及混合物配比等实验变量。