Disodium edetate

• BPDisodium Edetate
• JPDisodium Edetate Hydrate
• Ph. Eur.Disodium Edetate
• USP–NFEdetate Disodium

dinatrii edetas; disodium EDTA; disodium ethylenediaminetetraacetate; Dissolvine NA2; edetate disodium; Titriplex III; Trilon BD

Disodium dihydrogen (ethylenedinitrilo)tetraacetate dihydrate · [139-33-3]

UNII 8NLQ36F6MM · PubChem CID 8759

C10H14N2Na2O8·2H2O · 372.24 (dihydrate)

Antioxidant, chelating agent

Typical concentrations: 0.005–0.1% · Dosage forms: Liquid, Semi-solid, Sterile (parenteral/ophthalmic)

Used as a chelating agent in oral, topical, ophthalmic and parenteral preparations, usually at 0.005–0.1% w/v. It binds trace metal ions that catalyse oxidation, so it is often combined with antioxidants, and it enhances the activity of preservatives such as benzalkonium chloride against Gram-negative bacteria in eye drops. It is also used in cosmetics and foods.

A white, odourless, crystalline powder with a slightly acidic taste.

pH

about 4.0–5.5 (5% w/v aqueous solution)

pKa (edetic acid)

about 2.0, 2.7, 6.2 and 10.3

Melting point

decomposes at about 252 °C

Solubility

soluble about 1 in 11 of water; practically insoluble in ethanol, chloroform and ether

The solid is stable. Aqueous solutions can be sterilised by autoclaving and should be stored in alkali-free containers, because edetate can extract metal ions from glass.

Behaves as a weak acid, releasing carbon dioxide from carbonates and reacting with some metals to give hydrogen. Incompatible with strong oxidising agents, strong bases, polyvalent metal ions and metal alloys; it can also chelate metal-containing drugs, such as zinc in some insulin products.

Edetic acid is made from ethylenediamine, formaldehyde and sodium cyanide (or from ethylenediamine and chloroacetic acid); the disodium salt is obtained by partial neutralisation with sodium hydroxide and crystallised as the dihydrate.

Poorly absorbed from the gut and of low toxicity at excipient levels. Large intravenous doses bind calcium and can cause hypocalcaemia, tetany and cardiac arrhythmia, and fatal errors have occurred when it was confused with calcium disodium edetate. Edetate in nebuliser solutions has been associated with bronchoconstriction, and high doses may be nephrotoxic.

Observe normal precautions for the quantity handled. The dust may irritate the eyes and respiratory tract; wear eye protection and gloves.

Included in the FDA Inactive Ingredient Database (inhalation; injections; ophthalmic, oral, otic, rectal and topical preparations) and in parenteral and non-parenteral medicines licensed in Europe. JECFA has set an ADI for edetates of 0–2.5 mg/kg body weight (as calcium disodium edetate).

Calcium disodium edetate; edetic acid; tetrasodium edetate; trisodium edetate.

Disodium edetate is preferred to edetic acid in formulations because it is much more soluble in water. Its chelating capacity depends on pH, being weakest in strongly acidic solutions, and calcium or magnesium in the formulation will consume part of it.