International Numbering System (INS) for Food Additives:223
Food additives Europe numbers: E223
Functional Category
Antimicrobial preservative; antioxidant.
Applications in Pharmaceutical Formulation
Sodium metabisulfite is used as an antioxidant in oral, parenteral, and topical pharmaceutical formulations, at concentrations of 0.01–1.0% w/v, and at a concentration of approximately 27% w/v in intramuscular injection preparations. Primarily, sodium metabisulfite is used in acidic preparations; for alkaline preparations, sodium sulfite is usually preferred; see Section 18. Sodium metabisulfite also has some antimicrobial activity, which is greatest at acid pH, and may be used as a preservative in oral preparations such as syrups. In the food industry and in wine production, sodium metabisulfite is similarly used as an antioxidant, antimicrobial preservative, and antibrowning agent. However, at concentrations above about 550 ppm it imparts a noticeable flavor to preparations. Sodium metabisulfite usually contains small amounts of sodium sulfite and sodium sulfate.
Description
Sodium metabisulfite occurs as colorless, prismatic crystals or as a white to creamy-white crystalline powder that has the odor of sulfur dioxide and an acidic, saline taste. Sodium metabisulfite crystallizes from cold water as a hydrate containing seven water molecules.
Stability and Storage Conditions
On exposure to air and moisture, sodium metabisulfite is slowly oxidized to sodium sulfate with disintegration of the crystals.(1) Addition of strong acids to the solid liberates sulfur dioxide. In water, sodium metabisulfite is immediately converted to sodium (Naþ) and bisulfite (HSO3 ) ions. Aqueous sodium metabisulfite solutions also decompose in air, especially on heating. Solutions that are to be sterilized by autoclaving should be filled into containers in which the air has been replaced with an inert gas, such as nitrogen. The addition of dextrose to aqueous sodium metabisulfite solutions results in a decrease in the stability of the metabisulfite.(2) The bulk material should be stored in a well-closed container, protected from light, in a cool, dry place.
Incompatibilities
Sodium metabisulfite reacts with sympathomimetics and other drugs that are ortho- or para-hydroxybenzyl alcohol derivatives to form sulfonic acid derivatives possessing little or no pharmacological activity. The most important drugs subject to this inactivation are epinephrine (adrenaline) and its derivatives.(3) In addition, sodium metabisulfite is incompatible with chloramphenicol owing to a more complex reaction;(3) it also inactivates cisplatin in solution.(4,5) It is incompatible with phenylmercuric acetate when autoclaved in eye drop preparations.(6) S 654 Sodium metabisulfite may react with the rubber caps of multidose vials, which should therefore be pretreated with sodium metabisulfite solution.(7)
Safety
Sodium metabisulfite is widely used as an antioxidant in oral, topical, and parenteral pharmaceutical formulations; it is also widely used in food products. Although it is extensively used in a variety of preparations, sodium metabisulfite and other sulfites have been associated with a number of severe to fatal adverse reactions.(8–19) These are usually hypersensitivity-type reactions and include bronchospasm and anaphylaxis. Allergy to sulfite antioxidants is estimated to occur in 5–10% of asthmatics, although adverse reactions may also occur in nonasthmatics with no history of allergy. Following oral ingestion, sodium metabisulfite is oxidized to sulfate and is excreted in urine. Ingestion may result in gastric irritation, owing to the liberation of sulfurous acid, while ingestion of large amounts of sodium metabisulfite can cause colic, diarrhea, circulatory disturbances, CNS depression, and death. In Europe, the acceptable daily intake of sodium metabisulfite and other sulfites used in foodstuffs has been set at up to 3.5 mg/kg body-weight, calculated as sulfur dioxide (SO2). The WHO has similarly also set an acceptable daily intake of sodium metabisulfite, and other sulfites, at up to 7.0 mg/kg body-weight, calculated as sulfur dioxide (SO2).(20) LD50 (rat, IV): 0.12 g/kg(21)