A chromatographic determination of the stability of solutions of amlodipine benazepril & amlodipine besilate

Abstract

In aqueous solutions, drugs can be susceptible to chemical degradation by different mechanisms which decrease the stability of the drug leading to loss of potency and possibly to formation of degradation products. In this work, the stability of solutions prepared from amlodipine benazepril capsules and amlodipine besilate tablets stored under different conditions were investigated so as to determine whether degradation occurred with time and whether different storage conditions affected the degree of degradation of these products. The solutions were analyzed by HPLC, and a holding time interval between the preparation of solution and their analysis during which they were still stable was determined where relevant. Stability of the active was related to its ability to remain within the limits defined in the acceptance criteria. For each product, stability testing was carried out by preparing a stock standard solution, a working standard solution and a sample solution, the latter by dissolution of the relevant medicinal product. The solutions were incubated in different storage containers, protected from light at ambient temperature and under refrigerated conditions. The incubated working standard solutions and sample solutions, and a working standard solution freshly prepared from the incubated stock standard solution were analyzed against a freshly prepared working standard solution on day zero, day one, day two, day four and day seven, and the data obtained was assessed against the acceptance criteria for both mean percentage assay and coefficient of variation using statistical analysis. Amlodipine degraded significantly with time under all investigated storage conditions both in amlodipine besilate and amlodipine benazepril sample solutions. Thus, these were not considered to be stable over the time period studied even though in the case of amlodipine benazepril sample solutions, benazepril hydrochloride did not degrade significantly with time. Amlodipine in both amlodipine besilate and amlodipine benazepril sample solutions was not stable also till the first time interval. Therefore, a time interval during which sample solutions of the products were stable could not be determined. Amlodipine besilate standard solutions were considered as being stable over the time period studied whereas in the case of amlodipine benazepril standard solutions, one or both actives degraded when the solutions were stored under certain conditions. However, in this case a time interval during which the actives were considered as stable was determined. A kinetic model was fitted to the mean percentage assay of active which degraded with time. In both products, the peaks of degradants and placebo did not interfere with the peaks of the actives, therefore, the method for both products can be considered as being specific and it can be used in stability studies. Evaporation studies were carried out, where it was observed that evaporation of diluents occurred when stored under all sets of conditions thus decreasing the accuracy of the results obtained. Evaporation of standard diluent occurred to a larger extent than sample diluent.