Oxidative decomposition of pharmaceutical compounds is responsible for the instability of a considerable number of pharmaceutical preparations، e.g. steroids, vitamins, antibiotics, and epinephrine undergo oxidative degradation.
The most common form of oxidative decomposition occurring in pharmaceutical preparations is AUTOXIDATION, which involves a Free Radical Chain process, which come in following steps with a final result of inactive product.:
- Initiation
- Prolongation
- Hyperoxide decomposition
- Termination
Heavy metals, particularly those possessing two or more valency states, with a suitable oxidation reduction potential between them (coppper, iron, cobalt, and nickel) generally CATALYZE oxidative deteriorations.
As These metals play a role in:
- Reduce the length of the induction period (the time in which no measurable oxidation occurs).
- Increase the maximum rate of oxidation.
- Can affect the rates of chain initiation, propagation, and termination, as well as the rate of hydroperoxide decomposition.
In each case, their major function is to increase the rate of formation of free radicals.
Antioxidants are added to pharmaceutical formulations as redox systems possessing HIGHER oxidative potential than the drug that they are designed to protect, or as chain inhibitors of radical induced decomposition.
- Water-soluble antioxidants act by, preferentially undergoing oxidation in place of the drug.
- Oil-soluble antioxidants serve as free radical acceptors and inhibit the free radical chain process.
Sulfurous acid salts consume molecular oxygen present in solution. Structurally, other antioxidants have the property of losing a hydrogen free radical and/or an electron.
Sodium metabisulfite has been used extensively in the past and is still used to a considerable extent as an effective antioxidant. (not used with epinephrine as it produces epinephrine sulfonate)
Disodium edetate, is used widely as CHELATING AGENT for heavy metals in aqueous solutions.
Affect of pH
Bringing buffer solutions of readily oxidizable API's in acid range leading increasing in oxidation potential of the aqueous vehicle system makes a higher stability when oxidation is catalyzed by H+ or OH- ions. Thus, making more basic systems are more sensitive to oxidation.
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