R I

hno3

hno3

a hno3

hno3

Structure IV Miconazole nitrate

Structure III Econazole nitrate

Stabilisation against oxidation

Various precautions should be taken during manufacture and storage to minimise oxidation. The oxygen in pharmaceutical containers should be replaced with nitrogen or carbon dioxide; contact of the drug with heavy-metal ions such as iron, cobalt or nickel, which catalyse oxidation, should be avoided; and storage should be at reduced temperatures.

Antioxidants

It is very difficult to remove all of the oxygen from a container and even traces of oxygen are sufficient to initiate the oxidation chain. The

Structure IV Miconazole nitrate propagation of the chain reaction may be prevented or delayed by adding low concentrations of compounds that act as inhibitors. Such compounds are called antioxidants and interrupt the propagation by interaction with the free radical. The antioxidant free radical so formed is not sufficiently reactive to maintain the chain reaction and is eventually annihilated. The structures of some commonly used antioxidants are given in Scheme 4.6. Reducing agents such as sodium metabisulfite may also be added to formulations to prevent oxidation. These compounds are more readily oxidised than the drug and so protect it from e e

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