A Selective Voltammetric Method to Follow the Hydrolytic Degradation of Nitrendipine and Nisoldipine

Abstract

The development and application of a differential pulse voltammetric procedure for the hydrolytic degradation kinetic study of two wellknown 1,4-dihydropyridine type drugs, nitrendipine and nisoldipine are presented. The DPV procedure exhibited an adequate selectivity, repeatability and reproducibility with CV lower than 2%. The recoveries were higher than 98% with CV of 1.63% and 1.87% for nitrendipine and nisoldipine, respectively. Hydrolysis of each drug was carried out in ethanol=Britton-Robinson buffer (30=70) at different pHs and at controlled temperature of 40, 60 and 80 C. A significant degradation was observed at alkaline pH ( > pH 8) following a first order kinetic for both drugs. At pH 12 the decay constant values of 4.85 6 10 À2 h À1 for nitrendipine and 3.18 6 10 À2 h À1 for nisoldipine were obtained. Also, activation energies of 18 kcal=mol and 16 kcal=mol for nitrendipine and nisoldipine, respectively, were calculated. Furthermore, for the nitrendipine hydrolytic, degradation test in different solutions for parenteral use were studied. All the tested vehicles significantly increased the degradation of the drug, with the composition of solutions being the most relevant factor rather than the pH.

Electrolytic Oxidation of C4-Nitrofuryl 1,4-Dihydropyridines in Nonaqueous Medium

“…On the other hand, the aromatization of the 1,4-dihydropyridine ring to the corresponding pyridine derivative constitutes the most important in vivo reaction to terminate the pharmacological effect in the current clinically used drugs. 37 Finally, on the basis of findings presented here and other previous studies 27,29,31,33,34 Scheme 2 concerning the oxidation mechanism in an aprotic medium can be postulated. This mechanism is supported by two experimental facts: ͑i͒ the generation of the neutral dihydropyridyl radical intermediates C-centered was demonstrated by the trapping of these species with PBN and their characteristic spin adducts were determined by the ESR technique for the three compounds and ͑ii͒ the pyridine derivatives were identified by GC-MS as the final oxidation products in the aprotic medium.…”

“…21,22 Investigations dealing with the electrochemical oxidation of some 1,4-DHPs have previously been performed in both nonaqueous [23][24][25][26] and aqueous media. [27][28][29] We recently reported 30 the synthesis and electrochemical oxidation of some new 3,5-͑substituted͒-4-͑5Ј-nitro-2Ј-furyl͒-1,4-DHP derivatives in a protic medium. In that paper, a detailed study in aqueous medium on the electro-oxidation of these compounds is reported.…”