Chlorhexidine salts

Chlorhexidine is available in the form of acetate, gluconate, or hydrochloride. Chlorhexidine salts are incompatible with soaps and other anionic materials. Fabrics in contact with chlorhexidine solution may develop brown stains if bleached with hypochloride. 

For skin disinfection, chlorhexidine has been formulated as a 0.5% w/v solution in 70% v/v ethanol and, in conjunction with detergents, as a 4% w/v surgical scrub. Chlorhexidine salts may also be used in topical antiseptic creams, mouthwashes, dental gels, and in urology for catheter sterilization and bladder irrigation. 

Chlorhexidine salts have additionally been used as constituents of medicated dressings, dusting powders, sprays, and... 

Chlorhexidine occurs as an odorless, bitter tasting, white crystalline powder. See Section 17 for information on chlorhexidine salts. 

Chlorhexidine salts are widely used in pharmaceutical formulations in Europe and Japan for their antimicrobial properties. Although mainly used as disinfectants, chlorhexidine salts are also used as antimicrobial preservatives. 

As excipients, chlorhexidine salts are mainly used for the preservation of eye-drops at a concentration of 0.01% w/v generally the acetate or gluconate salt is used for this purpose. Solutions containing 0.002-0.006% w/v chlorhexidine gluconate have also been used for the disinfection of hydrophilic contact lenses. 

Bacteria (Gram-positive) chlorhexidine salts are active against most species the minimum inhibitory concentration (MIC) is normally in the range 1-10 pg/mL, although much higher concentrations are necessary for Streptococcus faecalis. Typical MIC values are shown in Table II. 

Fungi chlorhexidine salts are slowly active against molds and yeasts, although they are generally less potent in their inhibitory activity against fungi than against bacteria. Typical MIC values are shown in Table IV. 

Spores chlorhexidine salts are inactive against spores at normal room temperature. At 98-100°C there is some activity against mesophilic spores. 

In aqueous solution, chlorhexidine salts may undergo hydrolysis to form 4-chloroaniline. Following autoclaving of a 0.02% w/v chlorhexidine gluconate solution at pH 9 for 30 minutes at 120°C, it was found that 1.56% w/w of the original chlorhexidine content had been converted into 4-chloroaniline for solutions at pH 6.3 and 4.7 the 4-chloroaniline content was 0.27% w/w and 0.13% w/w, respectively, of the original gluconate content. In buffered 0.05% w/v chlorhexidine acetate solutions, maximum stability occurs at pH 5.6. 

Chlorhexidine salts, and their solutions, should be stored in well-closed containers, protected from light, in a cool, dry... 

Chlorhexidine salts are cationic in solution and are therefore incompatible with soaps and other anionic materials. Chlorhexidine salts are compatible with most cationic and nonionic surfactants, but in high concentrations of surfactant chlorhexidine activity can be substantially reduced owing to micellar binding. 

Chlorhexidine salts of low aqueous solubility are formed and may precipitate from chlorhexidine solutions of concentration greater than 0.05% w/v, when in the presence of inorganic acids, certain organic acids, and salts (e.g. benzoates, bicarbonates, borates, carbonates, chlorides, citrates, iodides, nitrates, phosphates, and sulfates). At chlorhexidine concentrations below 0.01% w/v precipitation is less likely to occur. 

Other substances incompatible with chlorhexidine salts include viscous materials such as acacia, sodium alginate, sodium carboxymethylcellulose, starch, and tragacanth. Also incompatible are brilliant green, chloramphenicol, copper sulfate, fluorescein sodium, formaldehyde, silver nitrate, and zinc sulfate. 

Chlorhexidine and its salts are widely used, primarily as topical disinfectants. As excipients, chlorhexidine salts are mainly used as antimicrobial preservatives in ophthalmic formulations. 

Chlorhexidine salts are included in nonparenteral and parenteral medicines licensed in the UK. Included in the Canadian List of Acceptable Non-medicinal Ingredients. 

Table 5.14 Aq ueous solubilities of tetracycline, erythromycin and chlorhexidine salts...

Arbcide. [ICI Spec. Chent IQ Surf. Belgium] Chlorhexidine salts preservative, bactericide. 

Other Chlorhexidine salts which are especially active against Pseudomonades are described by Warner et al (1980), without, however, having reached significant importance up to today ... 

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. 

Antiseptic eye lotions frequently used pre-, intra- and postoperatively at eye surgery may contain poUhexanide (PHMB), iodinated povidone or chlorhexidine salts. 

Low-volume eye lotions with antiseptics (iodinated povidone, polihexanide or chlorhexidine salts) for use in eye surgery must not contain preservatives. They are usually prepared aseptically in pharmacies using water for injection and sterile excipients, analogously to Table 10.18. Iodinated povidone eye lotion is thermally unstable and membrane filtration (<0.2 pm) has to be applied. 

Dequalinium acetate forms micelles with an aggregation number of 16, at a critical concentration of 4 x 10 moll [61]. The association of chlorhexidine salts has been examined by several workers with conflicting results. Heard and Ashworth [62] reported evidence from a variety of techniques for the association of both acetate and gluconate salts of this compound. Perrin and Witzke [63] determined a CMC for chlorhexidine gluconate from measurements of optical rotary dispersion techniques. Later workers [61] were, however, unable to detect any significant association of chlorhexidine acetate. 

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