Bonzalkonium Chloride

Category

Antimicrobial Preservative; Disinfectant; Solubilizing Agents; Wetting Agents

Molecular Formula

[C6H5CH2N(CH3)2R]C

Molecular Weight

360

Grade

Pharmceutical Excipients

Description

Benzalkonium chloride occurs as a white or yellowish-white amorphous powder, a thick gel, or gelatinous flakes. It is hygroscopic, soapy to the touch, and has a mild aromatic odor and very bitter taste.

UNII

F5UM2KM3W7

Chemical Name

Alkyldimethyl(phenylmethyl)ammonium chloride

CAS Number

8001-54-5

Synonyms

Alkylbenzyldimethylammonium chloride; alkyl dimethyl benzyl ammonium chloride; benzalkonii chloridum; BKC; Hyamine 3500; Pentonium; Zephiran

Administration route

Inhalation preparations, joint cavity, intradermal, intramuscular injection, ear, nose, ophthalmic preparations

Dosage Form

Inhalation; Intramuscular Injection; Nasal, Ophthalmic, Auricular, and Topical

Stability and Storage Conditions

Benzalkonium chloride is hygroscopic and may be affected by light, air, and metals. Solutions are stable over a wide pH and temperature range and may be sterilized by autoclaving without loss of effectiveness.Solutions may be stored for prolonged periods at room temperature. Dilute solutions stored in polyvinyl chloride or polyurethane foam containers may lose antimicrobial activity. The bulk material should be stored in an airtight container, protected from light and contact with metals, in a cool, dry place.

Source and Preparation

Benzalkonium chloride is formed by the reaction of a solution of Nalkyl-N-methylbenzamine with methyl chloride in an organic solvent suitable for precipitating the quaternary compound as it is formed.

Applications

Benzalkonium chloride is a quaternary ammonium compound used in pharmaceutical formulations as an antimicrobial preservative in applications similar to other cationic surfactants, such as cetrimide. In ophthalmic preparations, benzalkonium chloride is one of the most widely used preservatives, at a concentration of 0.01-0.02% w/v. Often it is used in combination with other preservatives or excipients, particularly 0.1% w/v disodium edetate, to enhance its antimicrobial activity against strains of Pseudomonas. In nasal, and otic formulations a concentration of 0.002-0.02% w/v is used, sometimes in combination with 0.002-0.005% w/v thimerosal. Benzalkonium chloride 0.01% w/v is also employed as a preservative in small-volume parenteral products. Benzalkonium chloride was also shown to enhance the topical penetration of lorazepam. Benzalkonium chloride is additionally used as a preservative in cosmetics.

Safety

Benzalkonium chloride is usually nonirritating, nonsensitizing, and is well tolerated in the dilutions normally employed on the skin and mucous membranes. However, benzalkonium chloride has been associated with adverse effects when used in some pharmaceutical formulations.Ototoxicity can occur when benzalkonium chloride is applied to the ear and prolonged contact with the skin can occasionally cause irritation and hypersensitivity. Benzalkonium chloride is also known to cause bronchoconstriction in some asthmatics when used in nebulizer solutions. Toxicity experiments with rabbits have shown benzalkonium chloride to be harmful to the eye in concentrations higher than that normally used as a preservative. However, the human eye appears to be less affected than the rabbit eye and many ophthalmic products have been formulated with benzalkonium chloride 0.01% w/v as the preservative. Benzalkonium chloride is not suitable for use as a preservative in solutions used for storing and washing hydrophilic soft contact lenses, as the benzalkonium chloride can bind to the lenses and may later produce ocular toxicity when the lenses are worn.Solutions stronger than 0.03% w/v concentration entering the eye require prompt medical attention. Local irritation of the throat, esophagus, stomach, and intestine can occur following contact with strong solutions (>0.1% w/v). The fatal oral dose of benzalkonium chloride in humans is estimated to be 1-3 g. Adverse effects following oral ingestion include vomiting, collapse, and coma. Toxic doses lead to paralysis of the respiratory muscles, dyspnea, and cyanosis. LD50 (mouse, oral): 150 mg/kg LD50 (rat, IP): 14.5 mg/kg LD50 (rat, IV): 13.9 mg/kg LD50 (rat, oral): 300 mg/kg LD50 (rat, skin): 1.42 g/kg

Incompatibilities

Incompatible with aluminum, anionic surfactants, citrates, cotton, fluorescein, hydrogen peroxide, hypromellose, iodides, kaolin, lanolin, nitrates, nonionic surfactants in high concentration, permanganates, protein, salicylates, silver salts, soaps, sulfonamides, tartrates, zinc oxide, zinc sulfate, some rubber mixes, and some plastic mixes.Benzalkonium chloride has been shown to be adsorbed to various filtering membranes, especially those that are hydrophobic or anionic.