Compressed Oxygen in Drug Stability Experiments

Abstract

A drug stability experiment accelerated by compressed oxygen was established. The stability of 10% ascorbic acid solution as a model was studied and the kinetic parameters were obtained with the newly established experimental method. Because ascorbic acid degrades under both anaerobic and aerobic conditions, the total rate constant k total can be expressed as: k total ‫؍‬k anaerobic ؉k aerobic , where k anaerobic and k aerobic are the rate constants of anaerobic and aerobic degradations, respectively. The k anaerobic can be expressed as k anaerobic ‫؍‬ A anaerobic · exp(؊E a,anaerobic /RT ) according to Arrhenius equation, and the k aerobic was found to be k aerobic ‫؍‬ A aerobic · exp(؊E a,aerobic /RT ) · p O 2 in our study.

Step Nonisothermal Method in Kinetics Studies of Captopril Oxidation under Compressed Oxygen

“…The relationship between k aerobic and oxygen pressure was expressed as Eq. (6) by Shi et al 13) k aerobic ＝A aerobic exp…”

“…Many papers reported that some drugs are unstable (or stable) under aerobic (or anaerobic) conditions, 1 11) but few reported the oxidation rate. 12,13) Captopril (I), an orally active inhibitor of the angiotensin-converting enzyme, is used widely to treat hypertension and congestive heart failure. Like all thiols, captopril is subjected to oxidation to form the dimer 14,15) captopril disulˆde (II).…”

“…13) The stability of ascorbic acid solution as a model was studied and the kinetic parameters were obtained with the method. Nevertheless, the disadvantage was still the requirement for a long experimental time and much eŠort.…”

The influence of reducing substances on the oxygen consumption in model solutions.

“…Existují různé mechanismy degradace kyseliny askorbové, rozdíl-né pro aerobní, nebo anaerobní podmínky (Shi a Zhan 2007). Prů-běh degradace askorbové kyseliny závisí na druhu vody a může při ní vznikat peroxid vodíku, přičemž se mohou tvořit různé degradační produkty.…”

“…Askorbová kyselina se může rozkládat aerobním i anaerobním způsobem, pokaždé za tvorby jiných produktů, např. diketogulonové kyseliny nebo furfuralu (Shi a Zhan 2007).…”