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.