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.