Ascorbic acid

International Numbering System (INS) for Food Additives: 300

Food additives Europe numbers: E300

Functional Category

Antioxidant; therapeutic agent.

Applications in Pharmaceutical Formulation

Ascorbic acid is used as an antioxidant in aqueous pharmaceutical formulations at a concentration of 0.01–0.1% w/v. Ascorbic acid has been used to adjust the pH of solutions for injection, and as an adjunct for oral liquids. It is also widely used in foods as an antioxidant. Ascorbic acid has also proven useful as a stabilizing agent in mixed micelles containing tetrazepam.(1

Description

Ascorbic acid occurs as a white to light-yellow-colored, nonhygroscopic, odorless, crystalline powder or colorless crystals with a sharp, acidic taste. It gradually darkens in color upon exposure to light.

Stability and Storage Conditions

In powder form, ascorbic acid is relatively stable in air. In the absence of oxygen and other oxidizing agents it is also heat stable. Ascorbic acid is unstable in solution, especially alkaline solution, readily undergoing oxidation on exposure to the air.(2,3) The oxidation process is accelerated by light and heat and is catalyzed by traces of copper and iron. Ascorbic acid solutions exhibit maximum stability at about pH 5.4. Solutions may be sterilized by filtration. The bulk material should be stored in a well-closed nonmetallic container, protected from light, in a cool, dry place

Incompatibilities

Incompatible with alkalis, heavy metal ions, especially copper and iron, oxidizing materials, methenamine, phenylephrine hydrochloride, pyrilamine maleate, salicylamide, sodium nitrite, sodium salicylate, theobromine salicylate, and picotamide.(4,5) Additionally, ascorbic acid has been found to interfere with certain colorimetric assays by reducing the intensity of the color produced.(6)

Safety

Ascorbic acid is an essential part of the human diet, with 40 mg being the recommended daily dose in the UK(7) and 60 mg in the USA.(8) However, these figures are controversial, with some advocating doses of 150 or 250 mg daily. Megadoses of 10 g daily have also been suggested to prevent illness although such large doses are now generally considered to be potentially harmful.(9–11) The body can absorb about 500 mg of ascorbic acid daily with any excess immediately excreted by the kidneys. Large doses may cause diarrhea or other gastrointestinal disturbances. Damage to the teeth has also been reported.(12) However, no adverse effects have been reported at the levels employed as an antioxidant in foods, beverages,(13) and pharmaceuticals. The WHO has set an acceptable daily intake of ascorbic acid, potassium ascorbate, and sodium ascorbate, as antioxidants in food, at up to 15 mg/kg bodyweight in addition to that naturally present in food.(14) LD50 (mouse, IV): 0.52 g/kg(15) LD50 (mouse, oral): 3.37 g/kg LD50 (rat, oral): 11.9 g/k

Anatomical Therapeutic Chemical Classification
A - Alimentary tract and metabolism
A11 Vitamins
A11G - Ascorbic acid (vitamin C), including combinations
A11GA Ascorbic acid (vitamin C), plain
Anatomical Therapeutic Chemical Classification
A - Alimentary tract and metabolism
A11 Vitamins
A11G - Ascorbic acid (vitamin C), including combinations
A11GB Ascorbic acid (vitamin C), combinations
Anatomical Therapeutic Chemical Classification
G - Genito-urinary system and sex hormones
G01 Gynecological antiinfectives and antiseptics
G01A - Antiinfectives and antiseptics, excluding combinations with corticosteroids
G01AD Organic acids
Anatomical Therapeutic Chemical Classification
S - Sensory organs
S01 Ophthalmologicals
S01X - Other ophthalmologicals
S01XA Other ophthalmologicals