Benzalkonium chloride

• BPBenzalkonium Chloride
• JPBenzalkonium Chloride
• Ph. Eur.Benzalkonium Chloride
• USP–NFBenzalkonium Chloride

Alkylbenzyldimethylammonium chloride; alkyldimethylbenzylammonium chloride; BKC; benzalkonii chloridum; Zephiran

Alkylbenzyldimethylammonium chloride (mixture of homologues) · [8001-54-5]

[C6H5CH2N(CH3)2R]Cl, where R is a mixture of alkyl chains (mainly C12 and C14) · average ≈ 360

Antimicrobial preservative

Typical concentrations: 0.01–0.02% ophthalmic · Dosage forms: Sterile (parenteral/ophthalmic)

The most widely used antimicrobial preservative in ophthalmic preparations, and also used in nasal and otic products, inhalation solutions, small-volume parenterals and topical products. Typical concentrations: ophthalmic 0.01–0.02% w/v; nasal and otic 0.002–0.02% w/v; parenteral about 0.01% w/v. It is often combined with disodium edetate to improve activity against Pseudomonas, and at higher concentrations it is used as a skin and surface antiseptic.

A white or yellowish-white amorphous powder, thick gel or gelatinous flakes. It is hygroscopic, soapy to the touch, has a mild aromatic odour and a very bitter taste.

Composition

mixture of alkylbenzyldimethylammonium chlorides with mainly C12 and C14 alkyl chains; pharmacopoeias set limits on homologue distribution

Solubility

very soluble in water, ethanol and acetone; practically insoluble in ether

pH

about 5–8 (10% w/v aqueous solution)

Surface activity

cationic surfactant; aqueous solutions foam strongly when shaken

Hygroscopic, and may be affected by light, air and metals. Aqueous solutions are stable over a wide pH and temperature range, can be autoclaved, and keep for long periods at room temperature. Dilute solutions stored in some plastic or rubber-closed containers may lose activity by sorption. Store in an airtight container, protected from light and from contact with metals.

Incompatible with anionic surfactants and soaps, citrates, iodides, nitrates, permanganates, salicylates, silver salts, tartrates, zinc oxide, zinc sulfate, fluorescein, hydrogen peroxide and some anionic polymers. Its activity is reduced by some nonionic surfactants at high concentrations, and it is adsorbed by some filter membranes, rubbers and plastics.

Produced by reacting a mixture of long-chain alkyldimethylamines with benzyl chloride, followed by purification.

At preservative concentrations it is generally well tolerated, but repeated or long-term use in eye drops can damage the corneal and conjunctival epithelium and aggravate dry eye, and it should be avoided with soft contact lenses. Nebulised solutions containing it can cause bronchoconstriction in asthmatic patients. Concentrated solutions are irritant to skin and mucous membranes, and EU product information carries specific warnings for medicines that contain it.

Concentrated material and solutions are irritant and corrosive to the eyes and skin; use gloves, eye protection and, where dust or mist is formed, respiratory protection.

Included in the FDA Inactive Ingredient Database (inhalation, intramuscular injection, nasal, ophthalmic, otic and topical preparations) and in parenteral and non-parenteral medicines licensed in Europe.

Benzethonium chloride; cetrimide; cetylpyridinium chloride; benzalkonium chloride solution.

Antimicrobial activity depends on the homologue mix: the C12 and C14 homologues are the most active, so the chain-length distribution should be controlled. Its tendency to bind to filters, tubing and containers can lower the effective concentration, which should be checked in the final pack.