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.
About this article: Merel Rachel Bout, Herman Vromans, Influence of commonly used excipients on the chemical degradation of enalapril maleate in its solid state: The role of condensed water, European Journal of Pharmaceutical Sciences, Volume 171, 2022, 106121, ISSN 0928-0987, https://doi.org/10.1016/j.ejps.2022.106121.
Table 1. A: Overview of all used materials for experiments.
|Divided class||Materials||Brand name, supplier, country|
|Enalapril maleate||Enalapril maleate, Zhejiang Huahai Pharmaceutical Co. Ltd., China|
|Disaccharides||Lactose monohydrate||Pharmatose 200 M, DFE Pharma, Germany|
|Spray-dried lactose||Supertab® 11SD, DFE Pharma, Germany|
|Anhydrous lactose||Supertab® 21AN, DFE Pharma, Germany|
|Celluloses||Microcrystalline cellulose||Vivapur® 101, JRS Pharma, Germany|
|Silicified microcrystalline cellulose||PROSOLV® SMCC 90, JRS Pharma, Germany|
|Starches||Potato starch||Native starch – potato based, Roquette, France|
|Corn starch||Meritena® Pharma 141, Tereos, France|
|Pregelatinized starch||C*Gel-Instant® 12,018, Cargill, United States|
|Partially pregelatinized starch||Starch 1500®, Colorcon, United States|
|Amylopectin||Amylopectin from maize, Sigma-Aldrich, The Netherlands|
|Super-disintegrants||Sodium starch glycolate||Primojel® type A, DFE Pharma, Germany|
|Sodium starch glycolate||Glycolys® type A, Roquette, France|
|Croscarmellose sodium||Ac-di-sol® SD-711, DuPont, United States|
|Crospovidone||Kollidon® CL, BASF, Germany|
|Silicon dioxide||ZEOFREE® 5162, Evonik Silica, Finland|