What is Benzalkonium Chloride?
Benzalkonium chloride, also known as BKC, BAK or Alkyl dimethyl benzyl ammonium chloride, is a quaternary ammonium salt and a cationic surfactant with broad antimicrobial activity against bacterial, yeasts, fungi and viruses. It is a mixture of alkybenzydimethylammonium chloride, the alkly groups having lengths of 8 to 18. The general chemical structure of Benzalkonium chloride is shown below:
n = 8, 10, 12, 14, 16, 18
| Chemical Name | Alkyldimethyl (phenylmethyl)ammonium chloride |
| CAS Registry Number | [8001-54-5] |
| Molecular Weight | 354 – 360. |
| Regulatory Status | PhEur; USP-NF |
Physicochemical Properties of Benzalkonium Chloride
Physical form
| White or yellowish-white powder, gel or gelatinous flakes | |
| Acidity/alkalinity | pH 5-8 (10% w/v aqueous solution) |
| Melting point | 40 oC |
| Partition coefficients | The octanol; water partition coefficient varies with the alkyl chain length of the homolog: 9.98 for C12, 32.9 for C14 and 82.5 for C16. |
| Solubility | Very soluble in water and ethanol. Aqueous solutions foam when shaken, have a low surface tension and possess detergent and emulsifying properties. |
How is Benzalkonium Chloride Used in Formulations?
Benzalkonium chloride is widely used in inhalations, IM injections, nasal, ophthalmic, and topical preparations as an antimicrobial preservative, antiseptic, disinfectant, solubilizing and wetting agent. It is used in similarly to other cationic surfactants, such as cetrimide.
In ophthalmic preparations, benzalkonium chloride is the preservative of choice and one of the most widely used preservatives, at concentrations of 0.01-0.02% w/v.
Antimicrobial activity can be enhanced, particularly against strains of Pseudomonas, benzalkonium chloride, through combination with other preservatives or excipients, such as 0.1% w/v Disodium edetate, phenylethanol or chlorhexidine.
In nasal formulations, benzalkonium chloride is used at a concentration of 0.002-0.02% w/v. Levels of 0.01% w/v have also been utilized in small-volume parenteral products.
Benzalkonium chloride can also be added to topical medical devices, antiseptic wipes and cosmetics as an alternative to parabens. It produces significantly less stinging or burning compared with isopropyl alcohol and hydrogen peroxide when used in topical products.
Any Comments and Useful Tips?
Benzalkonium chloride solutions are active against a wide range of bacteria, yeasts, and fungi. Activity is more marked against Gram-positive than Gram- negative bacteria but minimal against bacterial endospores and acid-fast bacteria. The antimicrobial activity of Benzalkonium Chloride is greatly dependent on the alkyl composition of the mixture.
Note that benzalkonium chloride has been associated with ototoxicity when applied to the ear. Prolonged contact with the skin may cause irritation and hypersensitivity. Benzalkonium Chloride is also known to cause bronchoconstriction in some asthmatics when used in nebulizer solutions.
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.
Local irritation of the throat, oesophagus, stomach, and intestine can occur following contact with strong solutions (>0.1% w/v).
References
[1] F.G. Casablancas, Novo Nordisk Pharmatech A/S.
[2] H.S. Bean, Preservatives for pharmaceuticals, J. Soc. Cosmet. Chem, 23 (1972) 703-720.
[3] B.B. Tarbox., et al., Benzalkonium chloride. A potential disinfecting irrigation solution for orthopaedic wounds, Clinical orthopaedics and related research, (1998) 255-261.
[4] C. Boukarim, S. Abou Jaoude, R. Bahnam, R. Barada, S. Kyriacos, Preservatives in liquid pharmaceutical preparations, J Appl Res, 9 (2009) 14-17.