Chlorhexidine preservative activity

In the weakly acidic preservatives, activity resides primarily in the unionized molecules and they only have significant efficacy at pHs where ionization is low. Thus, benzoic and sorbic acids (pKa = 4.2 and 4.75, respectively) have limited preservative usefulness above pH 5, while the 4(p)-hydroxybenzoate esters with their non-ionizable ester group and poorly ionizable hydroxyl substituent (pKa ca. 8.5) have moderate protective effect even at neutral pH levels. The activity of quaternary ammonium preservatives and chlorhexidine probably resides with their cations and are effective in products of neutral pH. Formulation pH can also directly influence the sensitivity of microorganisms to preservatives (see Chapter 11). 

Chlorhexidine is also cationic like BKC and exhibits similar incompatibilities. It is not as stable as BKC to autoclaving and may irritate the eyes. It tends to be more favoured in Europe than in the United States, and is particularly used in contact lens products. Chlorobutanol and phenylethyl aclohol are also widely used in ophthalmic products. However, chlorobutanol will hydrolyse in solution, and autoclaving is not usually possible without loss of preservative activity. It is also volatile and may be lost through the walls of plastic containers. 

As is apparent from the above information, there is no ideal disinfectant, antiseptic or preservative. All chemical agents have their limitations either in terms of their antimicrobial activity, resistance to organic matter, stability, incompatibility, irritancy, toxicity or corrosivity. To overcome the limitations of an individual agent, formulations consisting of combinations of agents are available. For example, ethanol has been combined with chlorhexidine and iodine to produce more active preparations. The combination of chlorhexidine and cetrimide is also considered to improve activity. QACs and phenols have been combined with glutaraldehyde so that the same effect can be achieved with lower, less irritant concentrations of glutaraldehyde. Some... 

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... 

Changes in the efficacy of preservatives vary exponentially with changes in concentration. The effect of changes in concentration (concentration exponent, t, Chapter 11) varies with the type of agent. For example, halving the concentration of phenol (r) = 6) gives a 64-fold (26) reduction in killing activity, while a similar dilution for chlorhexidine (r = 2)... 

Staph, aureus, whereas a 1 50000 dilution prevents growth of Vs. aeruginosa. Reports of pseudomonad contamination of aqueous chlorhex-idine solutions have prompted the inclusion of small amounts of ethanol or isopropanol. Chlorhexidine is ineffective at ambient temperatures against bacterial spores and M. tuberculosis. Limited antifungal activity has been demonstrated which unfortunately restricts its use as a general preservative. Skin sensitivity has occasionally been reported although, in general, chlorhexidine is well tolerated and nontoxic when applied to skin or mucous membranes and is an important preoperative antiseptic. 

In 24-hour collections of urine, glucose maybe preserved by adding 5 mL of glacial acetic acid to the container before starting the collection. The final pH of the urine is usually between 4 and 5, which inhibits bacterial activity. Other preservatives that have been proposed include 5 g of sodium benzoate per 24-hour specimen or chlorhexidine and 0.1% sodium nitrate (NaNs) with 0.01% benzethonium chloride. These may be inadequate, and urine should be stored at 4 °C during collection. Urine samples may lose as much as 40% of their glucose after 24 hours at room temperature. ... 

Chlorhexidine is mainly used as an active ingredient in disinfectants, deodorants and antiseptics and as a preservative in cosmetics and pharmaceuticals. The EC positive list of preservatives permitted for use in cosmetics mentions Chlorhexidine and its salts with a maximum authorized concentration of 0-3%. Formulating and using the active ingredient one has to remember its cationic nature which causes reduction of activity in the presence of organic matter, e.g. blood, serum, soaps and other anionic compounds. Another cause of activity loss is based on the very low water-solubility of certain Chlorhexidine salts borate, citrate, carbonate, bicarbonate, chloride or phosphate salts precipitate in systems containing such anions. 

Chlorhexidine is used as a preservative in the form of the very water-soluble chlorhexidine digluconate. The active... 

The minimum inhibition concentrations listed in Table 142 show that the Chlorhexidine digluconate formulation disposes of a broad efficacy spectrum. It may be utilized as a preservative in cosmetics, as an active ingredient in handwashes and scrubs, for dental and veterinary applications. - Percentage of use in US formulations chlorhexidine digluconate 0.09% chlorhexidine acetate 0.01% chlorhexidine dihydrochloride 0.02%. 

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