Many pharmaceutical products undergo oxidative deterioration upon storage because the therapeutic ingredients or adjuvants oxidize in the presence of atmospheric oxygen. Vitamins, essential oils, and almost all fats and oils can be oxidized readily. The decomposition can be particularly significant in disperse systems, such as emulsions, because of the large area of interfacial contact and because the manufacturing process may introduce air into the product. Many drugs commonly incorporated into emulsions are subjected to autoxidation and subsequent decomposition. Traces of oxidation products are undesirable as they are generally easily noticed by their smell and/or taste. The term "autoxidation" is used when the ingredient(s) in the product react(s) with oxygen without drastic external interference. Series of autoxidative reactions involve the initiation step or the formation of a free radical, the propagation step where the free radical is regenerated and reacts with more oxygen, followed by the termination step as the free radicals react with each other, resulting in the inactive products.

Antioxidants are classified into three main groups. The first group, comprising the true antioxidants, probably inhibits oxidation by reacting with free radicals, thus blocking the chain reaction. Examples include tocopherols, alkyl gallates, butylated hydroxyanisole (BHA), and butylated hydroxytoluene (BHT). They are commonly used at concentrations ranging from 0.001% to 0.1%. The second group, comprising the reducing agents, has a lower redox potential than the drug or other substances that it should protect and is therefore more readily oxidized. They may also react with free radicals. Examples are ascorbic and isoascorbic acids and the potassium or sodium salts of sulfurous acid. The latter group, such as sodium metabisulfite, has been reported to produce sensitivity reactions. The third group comprises the antioxidant synergists, including sequestering and chelating agents, which possess little antioxidant effect themselves but enhance the action of a true antioxidant by reacting with heavy metal ions that catalyze oxidation. The synergist class includes citric acid, tartaric acid, disodium edetate, and lecithin.

The selection of an appropriate antioxidant depends on factors such as stability, toxicity, efficiency, odor, taste, compatibility with other ingredients, and distribution phenomena between the two phases. Antioxidants that give protection primarily in the aqueous phase include sodium metabisulfite, ascorbic acid, thioglycerol, and cysteine hydrochloride. Oil-soluble antioxidants include lecithin, propyl gallate, ascorbyl palmitate, and BHT. Vitamin E has also been used, but its virtue as a natural antioxidant has been the subject of some controversy (the reader is referred to the chap. "Chemical Kinetics and Drug Stability" for more details).

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