Effect of the drug-matrix on the stability of enalapril maleate in tablet formulations

The chemical stability of enalapril maleate in tablet dosage forms consisti ng of different formulation excipients has been studied in this work. The i nfluence of various parameters such as hear, moisture, light and the drug-m atrix was investigated. The degradation of enalapril maleate has been follo wed by using an HPLC method. which was demonstrated to be specific, stabili ty indicating, accurate and precise. The degradation kinetics of enalalpril maleate in phosphate buffer solutions of pH values in the range of 2.2-10. 5 were observed to be psuedo first order throughout the whole pH range stud ied. Enalapril maleate alone showed high stability for temperature under dr y and humid conditions, however it became unstable when mixed with the drug -matrix in its tablet formulations and exposed to the same conditions. The pathway of degradation of enalapril maleate was found to be pH dependent. T he extent of degradation of two different enalapril maleate tablet formulat ions (product A of a basic drug-matrix and product B of an acidic drug-matr ix) has been investigated. The degree of degradation of the product with ac idic matrix was significantly less than that of the basic matrix under same temperature and humidity conditions. In fact, diketopiperazine and enalapr ilat degradants were mainly associated with thr degradation of tl;e product with the acidic matrix and that with the basic matrix, respectively. Dry e nalapril maleate powder showed some photolysis, which was more significant with daylight (3.3%) compared with that under UV light (0.2%). Although the product with the acidic matrix showed some photolysis but the effect was n ot pronounced and the % recovery of enalapril was almost complete and withi n the acceptable experimental errors. However, the product with the basic m atrix showed almost no response for photolysis. (C) 2001 Elsevier Science B .V. All rights reserved.