Antimicrobial Benzalkonium chloride

Preservatives Antimicrobial Benzalkonium chloride Benzyl alcohol Chlorhexidine Imidazolidinyl urea Phenol Potassium sorbate 1 Benzoic acid Bronopol Chlorocresol Paraben esters Phenoxyethanol Sorbic acid Antioxidants a-Tocopherol Ascorbic acid Ascorbyl palmitate Butylated hydroxyanisole Butylated hydroxytoluene Sodium ascorbate Sodium metabisulphite Chelating agents Citric acid Edetic acid... 

Fig. 10.8 A where the R substituents are alkyl or heterocyclic radicals to give compounds such as cetyltrimethylammonium bromide (cetrimide), cetylpyridinium chloride and benzalkonium chloride. Inspection of the stmctures of these compounds (Fig. 10.8B) indicates the requirement for good antimicrobial activily of having a chain length in the range Cg to Cig in at least one of the R substituents. In the pyridinium compounds (Fig. 10.8C) three of the four covalent links may be satisfied by the nitrogen in a pyridine ring. Polymeric quaternary ammonium salts such as polyquatemium 1 are finding increasing use as preservatives.

Examples of preservatives are phenylmercuric nitrate or acetate (0.002% w/v), chlorhexidine acetate (0.01 % w/v), thiomersal (0.01 % w/v) and benzalkorrium chloride (0.01 % w/v). Chlorocresol is too toxic to the comeal epithehum, but 8-hydroxyquinoline and thiomersal may be used in specific instances. The principal considerahon in relation to antimicrobial properties is the activity of the bactericide against Pseudomonas aeruginosa, a major source of serious nosocomial eye infections. Although benzal-konium chloride is probably the most active of the recommended preservatives, it cannot always be used because of its incompatibility with many compounds commonly used to treat eye diseases, nor should it be used to preserve eye-drops containing anaesthetics. Since benzalkonium chloride reacts with natural mbber, silicone or butyl rabber teats should be substituted. Since silicone mbber is permeable to water vapour, products should not be stored for more than 3 months after manufacture. As with all mbber components, the mbber teat should be pre-equilibrated with the preservative prior to... 

Substances that have been used as preservatives for disperse systems include chlorocresol, chlorobutanol, benzoates, phenylmercuric nitrate, parabens, and others [76,77]. The use of cationic antimicrobial agents such as quaternary ammonium compounds (e.g., benzalkonium chloride) is contraindicated in many cases because they may be inactivated by other formulation components and/or they may alter the charge of the dispersed phase. Clay suspensions and gels should be adequately preserved with nonionic antimicrobial preservatives. The use of preservatives is generally limited to products that are not intended for parenteral use. Intravenous injectable... 

Nebulizer formulation conforms to sterile product preparation, which means that drug stability in solution in the presence of additives must be evaluated. Historically, it was sufficient to use antimicrobial agents in the formulation, notably benzalkonium chloride. Adding antimicrobials is not now considered an acceptable approach to the formulation of nebulizer solutions. The solubility of the drug is important since it may impact upon the performance of the solution in a selected nebulizer. Additives may form complexes with the drug. 

Benzalkonium chloride ( ) is used as an antimicrobial preservative in Nasonex. It is quantifiable using a HPLC method with a column that has a cyano group chemically bonded to porous silica particles. The HPLC was equipped with a UV-Vis detector, a 150 mm x 4.6 mm, 3- jm Spherisorb S3 CN column. The mobile phase consisted of 45% acetonitrile in 0.05 M phosphate buffer (pH 6.0). The flow rate was set at 1 mL/min. The following procedure was used for sample and standard preparations. About 2.5 g of Nasonex was transferred into a 25-mL volumetric flask. This was diluted to volume with acetonitrile and... 

The quaternary surfactants benzalkonium chloride (BAG) and benzethonium chloride are preferred by many manu-fecturers because of their stabihty, excellent antimicrobial properties in acid formulation, and long shelf life. They exhibit toxic effects on both the tear film and the corneal epithelium and have long been known to increase drug penetration. The toxicity of these compounds may be increased by the degree of acidity of the formulation. 

Other components, is rendered sterile separately, asep-tically weighed, and incorporated in preparing a final product that meets the sterility requirement. This is done because of difficulty in terminal product sterilization, such as lack of penetration of steam into the ointment base and instability of components owing to high dry heating. Antimicrobial preservatives such as methylparaben (0.05%) and propylparaben (0.01%) and its combinations phenylmercuric acetate (0.0008%), chlorobutanol (0.5%),and benzalkonium chloride (0.008%) are used as needed. 

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. 

Karabit MS, Juneskans OT, Lundgren P. Studies on the evaluation of preservative efficacy III the determination of antimicrobial characteristics of benzalkonium chloride. Int J Pharm 1988 46 141-147. 

At pH 7, tragacanth has been reported to considerably reduce the efficacy of the antimicrobial preservatives benzalkonium chloride, chlorobutanol, and methylparaben, and to a lesser extent that of phenol and phenylmercuric acetate. However, at pH < 5 tragacanth was reported to have no adverse effects on the preservative efficacy of benzoic acid, chlorobutanol, or methylparaben. ... 

A CVC coated with an antiseptic combination, silver chloride and benzalkonium chloride(BKC), in a polymer(PU) matrix was developed. The antimicrobial efficacy and the ability to prevent surface colonisation. 

All ophthalmic medications are potentially absorbed into the systemic circulation (Figure 63-3), so undesirable systemic side effects may occur, as well as potential local toxic effects due to hypersensitivity reactions or to direct toxic effects on the cornea, conjunctiva, periocular skin, and nasal mucosa. Eyedrops and contact lens solutions commonly contain preservatives such as ben-zalkonium chloride, chlorobutanol, and chelating agents for their antimicrobial effectiveness. In particular, benzalkonium chloride may cause a punctate keratopathy or toxic ulcerative keratopathy. 

The chemical modification of CS biopolymers via reductive amination, to yield alkylated CS derivatives, and further quaternisation result in very efficient antibacterial materials the degree of activity is correlated to the length of the alkyl chain and bacterial strain. The most active CS derivatives are more selective at killing bacteria than the quaternary ammonium disinfectants, cetylpyridinium chloride and benzalkonium chloride, and AMP. Vanillin can be used as a crosslinker of CS nsing this approach, functionalised antimicrobial polymers based on CS, vanillin. Tween 60 and so on may be easily prepared. Imino-CS biopolymer films, prepared by the acid condensation of the amino groups of CS with various aldehydes, can be used as functional biodynamic materials. 

Cationic surface active agents such as benzalkonium chloride and cetyltrimethylammonium bromide (Figure 1) have use as antibacterial agents, i.e., disinfectants and antiseptics, and have the advantage that the antimicrobial action is combined with a cleaning action associated with their detergent activity. 

Hexahydro-1,3,5-triethyl-s-triazine antimicrobial, paper/paperboard pigments aq./fatty food-contact Hexahydro-1,3,5-triethyl-s-triazine antimicrobial, paper/paperboard sizings aq./fatty food-contact Hexahydro-1,3,5-triethyl-s-triazine antimicrobial, paper/paperboard nonalcoholic/dry food-contact Dodecylguanidine hydrochloride Dodine antimicrobial, personal care Diazolidinyl urea Glutaral Lapyrium chloride Laurylpyridinium chloride Ricinoleamidopropyl trimonium methosulfate Steapyrium chloride antimicrobial, pharmaceutical ointments Tea tree (Melaleuca alternifolia) oil antimicrobial, pharmaceutical topicals Captan p-Chloro-m-cresol Diazolidinyl urea DMDM hydantoin Methylchloroisothiazolinone Methylisothiazolinone Nonoxynol iodine Quaternium-15 Stearalkonium chloride antimicrobial, pharmaceuticals Aluminum formate Aluminum phenolsulfonate Ammonium iodide Benzalkonium chloride Benzethonium chloride... 

Benzalkonium chloride is the most widely used preservative in ophthalmology. It is a quaternary ammonium compound that acts as an antimicrobial agent by denaturing proteins and disrupting cytoplasmic membranes. 

Neither anionic nor non-ionic surfactants impair Bronopol s antimicrobial efficacy. For that reason the product is a most suitable preservative for detergent solutions, bath foams, shampoos and hair rinses. Bronopol is also compatible with quaternary ammonium compounds (Section 16.1) and cationic active ingredients such as benzalkonium chloride. 

Most ready-to-use liquid preparations for nebuUsatimi are supplied in single-dose vials and according to the European Pharmacopoeia, they have to be sterile and preservative-free. When they are supplied in multidose containers, they have to be sterile if they do not contain an antimicrobial preservative or when the preparation does not have adequate antimicrobial properties itself. The multidose containers have to be designed to prevent microbial contamination of their contents during storage and use. A wide variety of preservatives is available but some of them, like phenol, bisulfites, edetate and benzalkonium chloride can cause airway irritation and result in bronchoconstriction or reduce the efficacy of the medicine [57]. Other compounds such as chlorobutanol, methyl- and propyl-parahydroxybenzoate and also benzalkonium chloride are cUiotoxic at... 

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