Chlorhexidine gluconate

• BPChlorhexidine Gluconate Solution
• JPChlorhexidine Gluconate Solution
• Ph. Eur.Chlorhexidine Digluconate Solution
• USP–NFChlorhexidine Gluconate Solution

CHG; chlorhexidine digluconate; chlorhexidini digluconatis solutio; Hibiclens; Hibiscrub; Hibitane

1,1′-Hexamethylenebis[5-(4-chlorophenyl)biguanide] di-D-gluconate (supplied as an aqueous solution of about 20% w/v) · [18472-51-0]

UNII MOR84MUD8E · PubChem CID 9552081

C22H30Cl2N10·2C6H12O7 · 897.76

Antimicrobial preservative

Typical concentrations: — · Dosage forms: Liquid, Semi-solid

A bisbiguanide antiseptic used as an antimicrobial preservative in eye drops, contact lens solutions and topical products at about 0.0025–0.01% w/v, and as the active ingredient in antiseptic products: about 0.05% for wound cleansing, 0.12–0.2% in mouthwashes, 0.5% in 70% ethanol or 2% in 70% isopropyl alcohol for skin preparation, and 4% in surgical hand scrubs. Its persistent binding to skin and mucosa gives a prolonged residual effect.

The pharmacopoeial material is a clear or slightly opalescent, almost colourless or pale yellow aqueous solution containing about 20% w/v chlorhexidine digluconate; it is practically odourless and has a bitter taste.

Content

19.0–21.0% w/v of chlorhexidine digluconate in the pharmacopoeial solution

Relative density

about 1.06–1.07

pH

5.5–7.0 (solution diluted to 5% w/v)

Solubility

miscible with water; miscible with limited proportions of ethanol and acetone

Antimicrobial spectrum

broad activity against Gram-positive and Gram-negative bacteria and yeasts; weaker against Pseudomonas and Proteus; not sporicidal

Most stable between about pH 5 and 8; above about pH 8 the chlorhexidine base precipitates, and in acid solution activity falls. At high temperatures it hydrolyses to give 4-chloroaniline, so heat sterilisation of solutions is limited and the impurity must be controlled. Store protected from light in a well-closed container. Dilute aqueous solutions may become contaminated with resistant Gram-negative bacteria and should be sterilised or freshly prepared.

Incompatible with soaps and other anionic substances such as sodium lauryl sulfate, carbomers, alginates and tragacanth. It forms sparingly soluble salts with borates, bicarbonates, carbonates, chlorides, citrates, phosphates and sulfates, which may precipitate from more concentrated solutions. Non-ionic surfactants, insoluble powders and cork reduce its activity, and hard water can cause precipitation.

Chlorhexidine base is prepared by reacting hexamethylenebis(dicyandiamide) with 4-chloroaniline hydrochloride; the base is then dissolved in water with gluconic acid (as glucono-δ-lactone) to give the digluconate solution.

Poorly absorbed through skin and mucosa and generally well tolerated, but skin irritation and allergic reactions occur, including rare severe anaphylaxis, about which regulators have issued warnings. It should not come into contact with the middle ear, meninges or brain, and concentrated solutions must be kept out of the eyes. Mouthwashes can stain teeth and the tongue and alter taste.

Observe normal precautions for the quantity handled. The concentrated solution is irritant to the eyes; wear eye protection and gloves.

Widely used as an active antiseptic in licensed and over-the-counter medicines and in medical devices; as an excipient it is used at low concentrations as a preservative in some non-parenteral products.

Chlorhexidine acetate (diacetate); chlorhexidine hydrochloride (dihydrochloride); alexidine; polyhexanide.

The digluconate is chosen for liquid products because it is much more water-soluble than the acetate or hydrochloride salts. Dilute with purified (soft) water rather than tap water, avoid cork closures, and keep the pH between about 5 and 7 for the best balance of activity and stability.