Influence of commonly used excipients on the chemical degradation of enalapril maleate in its solid state: The role of condensed water.

The physicochemical stability of enalapril maleate was investigated in the presence of fourteen different excipients divided into four different classes. The extent of a drug-excipient interaction was investigated by following the chemical stability using HPLC. It was found that there is a certain order in the stability of enalapril maleate. Enalapril maleate remained most stable in the presence of: disaccharides > celluloses > starches > superdisintegrants. The amount of degradation can be related to the excipient characteristics. A material with a higher water sorption capacity and lower crystallinity presents a more reactive particle surface. It was revealed that the condensation layer deposited on the surface of the excipient is responsible for the degradation of enalapril maleate. A confirmation was found by changing the surface of the excipient and influencing the environmental humidity that allowed a variable build-up of the condensation layer. For this particle-particle interaction, the microenvironmental pH only presents a minor effect as it was found to not be a determining factor for degradation. Moreover, there appears to be a firm relationship between the degradation of enalapril maleate and the water sorption-activity of excipients.

Study on the Mechanism Responsible for the Incompatibility of Enalapril Maleate with Sodium Starch Glycolate.

Enalapril maleate (EM) is known to suffer from incompatibilities in the solid state. This study investigates the destabilizing effect of sodium starch glycolate (SSG) on EM. This was done by varying the mixing ratio and moisture content of binary mixtures. Differential scanning calorimetry and microscopy show a loss of crystallinity of EM at the contact surface with SSG. It is shown that this is followed by decomposition of E to diketopiperazine (DKP). These phenomena are modulated by moisture. The environmental pH turned out to be crucial; when the zwitterion is formed at the appropriate pH, ring closure into DKP is promoted.