Maleic acid

• BPMaleic Acid
• Ph. Eur.Maleic Acid
• USP–NFMaleic Acid

cis-Butenedioic acid; (Z)-but-2-enedioic acid; cis-1,2-ethylenedicarboxylic acid; toxilic acid; acidum maleicum

(Z)-Butenedioic acid · [110-16-7]

UNII 91XW058U2C · PubChem CID 444266

C4H4O4 · 116.07

pH adjuster, buffering agent

Typical concentrations: — · Dosage forms: Solid

Used as an acidulant and pH adjuster in oral, topical and parenteral formulations, and as an antioxidant synergist in fats and oils, at low concentrations. Its main pharmaceutical use is as a salt-forming acid for basic drugs (maleate salts).

White crystalline powder or colourless crystals with a faint odour and an astringent, sour taste.

Melting point

≈ 130 °C

pKa

≈ 1.9 and ≈ 6.1 (25 °C)

Solubility

very soluble in water; freely soluble in ethanol (95%); slightly soluble in ether

Density

≈ 1.59 g/cm³

Stable at room temperature. On heating above its melting point it isomerises to fumaric acid and can lose water to form maleic anhydride. Store in a well-closed container in a cool, dry place.

Incompatible with strong oxidising agents and bases. Its activated double bond can add to nucleophiles such as amines and thiols (Michael addition), which has been reported as a degradation route for some maleate salts.

Produced by hydrolysis of maleic anhydride, which is made by catalytic oxidation of benzene or n-butane.

At the low levels used as an excipient it is not regarded as a significant hazard, but the concentrated acid is irritant to the skin, eyes and mucous membranes. High doses have caused renal tubular damage in animal studies.

Irritant: eye protection, gloves and protective clothing are recommended, and dust should not be inhaled; work with adequate ventilation.

Included in the FDA Inactive Ingredient Database (injections and oral preparations). Many marketed drugs are maleate salts.

Fumaric acid (the trans isomer); malic acid; succinic acid.

When choosing maleate as a counter-ion, check for Michael-addition adducts with the drug or other excipients during stability testing.