Bronopol

• BPBronopol

2-bromo-2-nitro-1,3-propanediol; β-bromo-β-nitrotrimethyleneglycol; Bronidiol; bronopolum; Bronosol; Myacide

2-Bromo-2-nitropropane-1,3-diol · [52-51-7]

UNII 6PU1E16C9W · PubChem CID 2450

C3H6BrNO4 · 199.99

Antimicrobial preservative

Typical concentrations: 0.01–0.1% · Dosage forms: Semi-solid, Liquid

Bronopol is an antimicrobial preservative used mainly in topical pharmaceutical preparations and in cosmetics and toiletries, typically at 0.01–0.1% w/v. Its value lies in its strong activity against Gram-negative bacteria such as Pseudomonas, so it is often combined with an antifungal preservative (for example a paraben) to cover yeasts and moulds.

White or almost white crystals or crystalline powder, odourless or with only a faint characteristic odour.

Melting point

about 130 °C, with decomposition

Solubility

freely soluble in water, ethanol and propylene glycol; soluble in glycerol; poorly soluble in mineral oil and other non-polar solvents

Partition behaviour

strongly favours the aqueous phase of emulsions, so little preservative is lost to the oil phase

Antimicrobial spectrum

broad activity against Gram-positive and Gram-negative bacteria, including Pseudomonas aeruginosa; weaker against yeasts and moulds

Stable as the solid and in acidic aqueous solution. In neutral and especially alkaline solution, and on heating, it decomposes with release of formaldehyde and nitrite, and solutions may turn yellow or brown, particularly on exposure to light. Store in a well-closed container, protected from light, in a cool, dry place.

Its activity is markedly reduced by sulfhydryl compounds such as cysteine and by reducing agents such as sodium metabisulfite and sodium thiosulfate. Aluminium packaging components may be attacked. The nitrite released on degradation can react with secondary and tertiary amines and amides to form nitrosamines, so bronopol should not be combined with such compounds.

Produced by condensing nitromethane with formaldehyde under alkaline conditions to give a nitropropanediol intermediate, which is then brominated.

At the concentrations used as a preservative bronopol is generally well tolerated on the skin, but it is an irritant at higher concentrations and has caused allergic contact dermatitis. The possible formation of nitrosamines in formulations containing amines is the main concern with its use.

Observe normal precautions for the quantity handled. The powder is irritant to the eyes, skin and respiratory tract; wear eye protection and gloves and avoid generating dust.

Included in the FDA Inactive Ingredient Database (topical preparations) and in non-parenteral medicines licensed in the UK. Permitted as a preservative in cosmetics in the EU up to 0.1%, with the requirement that conditions favouring nitrosamine formation are avoided.

Other preservatives used in topical products, such as imidurea, phenoxyethanol and the parabens.

Formulate bronopol at slightly acidic pH, ideally around 4–6, to limit degradation, and avoid heating it during manufacture; add it to the cooled aqueous phase. Check finished products containing amine-type ingredients (for example triethanolamine) for nitrosamines.