Methylparaben

• BPMethyl Hydroxybenzoate
• JPMethyl Parahydroxybenzoate
• Ph. Eur.Methyl Parahydroxybenzoate
• USP–NFMethylparaben

Methyl hydroxybenzoate; methyl parahydroxybenzoate; methyl 4-hydroxybenzoate; methylis parahydroxybenzoas; Nipagin M; E218

Methyl 4-hydroxybenzoate · [99-76-3]

UNII A2I8C7HI9T · PubChem CID 7456

C8H8O3 · 152.15

Antimicrobial preservative

Typical concentrations: 0.015–0.2% oral · 0.02–0.3% topical · Dosage forms: Liquid, Semi-solid

Widely used as an antimicrobial preservative in oral, topical and parenteral products, cosmetics and foods, often combined with propylparaben for a broader spectrum. It is most active against moulds and yeasts and effective over pH 4–8. Typical concentrations: intramuscular, intravenous and subcutaneous injections 0.065–0.25%; inhalation solutions 0.025–0.07%; ophthalmic preparations 0.015–0.2%; oral solutions and suspensions 0.015–0.2%; topical preparations 0.02–0.3%; vaginal preparations 0.1–0.18%.

Colourless crystals or a white crystalline powder, odourless or almost odourless, with a slight burning taste.

Melting point

125–128 °C

pKa

≈ 8.2

Solubility

slightly soluble in water (about 1 in 400 at 25 °C; more soluble in hot water); freely soluble in ethanol (95%), acetone and propylene glycol

Partition coefficient

log P (octanol/water) ≈ 1.9

Effective pH range

about 4–8; activity falls as the phenol ionises at higher pH

Aqueous solutions at pH 3–6 can be sterilised by autoclaving without significant decomposition and are stable for years at room temperature; at pH 8 and above hydrolysis to p-hydroxybenzoic acid becomes rapid. Store in a well-closed container in a cool, dry place.

Antimicrobial activity is markedly reduced by non-ionic surfactants such as polysorbate 80 (micellar binding) and by binding to polymers and adsorbents such as magnesium trisilicate, talc, bentonite, tragacanth and sodium alginate. It is also incompatible with essential oils, sorbitol and atropine, may be absorbed by some plastics, and is discoloured by iron and hydrolysed by strong acids and bases.

Prepared by esterification of p-hydroxybenzoic acid with methanol.

Generally regarded as non-toxic and non-irritant at the concentrations used. Hypersensitivity reactions, usually of the delayed contact type, occur mainly with topical use; immediate reactions and bronchospasm after parenteral use are rare. Weak oestrogenic activity has been shown in vitro, which has led to restrictions on some longer-chain parabens, but methylparaben is considered of low concern; EFSA has set a group ADI of 0–10 mg/kg body weight for methyl and ethyl paraben.

Observe normal precautions for the quantity handled. Avoid generating dust; eye protection, gloves and a dust mask are recommended.

GRAS listed. Accepted as a food additive in Europe (E218). Included in the FDA Inactive Ingredient Database (intramuscular, intravenous and subcutaneous injections; inhalation; ophthalmic, oral, otic, rectal, topical and vaginal preparations) and in parenteral and non-parenteral medicines licensed in Europe. In EU cosmetics it is permitted up to 0.4% (as acid) as a single ester and 0.8% for mixtures of esters.

Ethylparaben; propylparaben; butylparaben; methylparaben sodium.

Because its water solubility is low, it is usually dissolved in hot water or in a glycol before addition. Combining it with propylparaben (commonly about 0.18% methyl with 0.02% propyl) or adding 2–5% propylene glycol improves preservative performance; efficacy should always be confirmed by a preservative efficacy test in the final formulation.