CHLORHEXIDINE HYDROCHLORIDE

Chlorhexidine hydrochloride is the cationic salt form of chlorhexidine, appearing as a white to off-white crystalline powder with good chemical stability and low volatility under recommended storage conditions.
Chlorhexidine hydrochloride's strong cationic nature enables interaction with negatively charged bacterial cell walls, causing cytoplasmic leakage at low concentrations and complete cell lysis at higher concentrations.
Because it provides prolonged antimicrobial activity through surface adsorption (substantivity), chlorhexidine hydrochloride is extensively used in antiseptic, dental, pharmaceutical, and clinical hygiene formulations.

CAS Number: 3697-42-5
EC Number: 222-018-2
Molecular Formula: C22H32Cl4N10
Molecular Weight: 578.37

Synonyms: Chlorhexidine disinfectant, Chlorhexidine pharmaceutical grade, CHLORHEXIDINE HYDROCHLORIDE, Chlorhexidine dihydrochloride, 3697-42-5, Chlorhexidine HCl, Dantroche hibitane, AY-5312, E64XL9U38K, NSC-756679, 2,4,11,13-Tetraazatetradecanediimidamide, N,N''-bis(4-chlorophenyl)-3,12-diimino-, dihydrochloride, DTXCID5027144, DTXSID7047144, Chlorhex hcl, 1,1'-Hexamethylenebis(5-(4-chlorophenyl)biguanide) dihydrochloride, 1,1'-Hexamethylenebis[5-(4-chlorophenyl)biguanide] Dihydrochloride, Nolvasan Cap-Tabs, Nolvasan Suspension, RefChem:54790, Hydrochloride, Chlorhexidine, 223-026-6, Chlorhexidine (dihydrochloride), chlorhexidinedihydrochloride, Arlacide H, N1,N14-Bis(4-chlorophenyl)-3,12-diimino-2,4,11,13-Tetraazatetradecanediimidamide dihydrochloride, NCGC00256637-01, 2,4,11,13-Tetraazatetradecanediimidamide, N,N'-bis(4-chlorophenyl)-3,12-diimino-, dihydrochloride, CHLORHEXIDINE DIHYDROCHLORIDE [MI], CHLORHEXIDINE DIHYDROCHLORIDE [EP MONOGRAPH], 1,1'-HEXAMETHYLENEBIS(5-(P-CHLOROPHENYL)BIGUANIDE)DIHYDROCHLORIDE, Certified Reference Material, N-(4-chlorophenyl)-1-3-(6-{N-[3-(4-chlorophenyl)carbamimidamidomethanimidoyl]amino}hexyl)carbamimidamidomethanimidamide dihydrochloride, Caswell No. 481F, Chlorhexidinium dichloride, MFCD00068998, Chlorhexidine 2HCl, 1,1'-Hexamethylenebis(5-(p-chlorophenyl)biguanide) dihydrochloride, 2,4,11,13-TEtraazatetradecanamide, 14-[(4-chlorophenyl)amino]-3,12,14-triimino, EINECS 223-026-6, EPA Pesticide Chemical Code 481700, UNII-E64XL9U38K, Dantroche hibitane (TN), Biguanide, 1,1'-hexamethylenebis(5-(p-chlorophenyl)-, dihydrochloride, Chlorhexidine dihydrochloirde, Chlorhexidine hydrochloride [USAN:USP:BAN:JAN], SPECTRUM1500177, CHEMBL1484251, 

Chlorhexidine hydrochloride is a broad-spectrum antimicrobial agent belonging to the bisbiguanide class, widely used for its strong antiseptic and disinfectant properties.
Chlorhexidine hydrochloride is a white to off-white crystalline powder that is readily soluble in water and alcohol, and is typically supplied in hydrochloride salt form to enhance stability and solubility.

Chlorhexidine hydrochloride is effective against a wide range of Gram-positive and Gram-negative bacteria, as well as some fungi and enveloped viruses, by disrupting microbial cell membranes and causing leakage of intracellular components.
Due to its high antimicrobial efficacy, low systemic absorption, and good safety profile when used as directed, Chlorhexidine hydrochloride is commonly used in pharmaceutical formulations, medical disinfectants, oral care products, wound care solutions, and personal hygiene applications.

Chlorhexidine hydrochloride is the cationic salt form of chlorhexidine, a bactericidal detergent.
Chlorhexidine hydrochloride has strong bactericidal activity and is used for in vitro bactericidal assays as a positive control.

Chlorhexidine hydrochloride functions as a bactericidal agent by interacting with the negatively charged bacterial cell wall.
Contact of the cationic salt with the cell wall causes cytosolic leakage at low chlorohexidine HCl concentrations and cell lysis at higher concentrations.

Duration of antibacterial effects has been shown to be enhanced by incorporating Chlorhexidine hydrochloride into human albumin microspheres.
This lengthened antibacterial activity against Escheria coli, Staphylococcus aureus and Pseudomonas aeruginosa.

Chlorhexidine hydrochloride occurs as a white, crystalline powder.
Chlorhexidine hydrochloride is odorless, and has a bitter taste.

Chlorhexidine hydrochloride is soluble in formic acid, slightly soluble in methanol and in warm methanol, and practically insoluble in water, in ethanol (95) and in diethyl ether.
Chlorhexidine hydrochloride is gradually colored by light.

Chlorhexidine hydrochloride is a high-efficacy antimicrobial compound of the bisbiguanide family, formulated as the hydrochloride salt to improve aqueous solubility, stability, and handling in pharmaceutical and medical applications.
Chlorhexidine hydrochloride typically appears as a white to off-white crystalline powder with low volatility and good chemical stability under recommended storage conditions.
The molecule exhibits strong cationic properties, allowing it to bind effectively to negatively charged bacterial cell walls and membranes, where it disrupts membrane integrity, alters permeability, and ultimately leads to leakage of cellular components and microbial cell death.

Chlorhexidine hydrochloride demonstrates broad-spectrum antimicrobial activity, being particularly effective against Gram-positive bacteria and also active against many Gram-negative bacteria, fungi, and enveloped viruses, while showing limited activity against bacterial spores and non-enveloped viruses.
One of its key advantages is its substantivity, meaning Chlorhexidine hydrochloride can adsorb onto skin, mucous membranes, and dental surfaces and continue to exert antimicrobial effects over an extended period.
Chlorhexidine hydrochloride is extensively used in antiseptic solutions, surgical scrubs, wound care products, oral rinses, dental formulations, pharmaceutical preparations, and personal hygiene products, where reliable antimicrobial performance and prolonged activity are essential.

Uses of Chlorhexidine Hydrochloride:
Chlorhexidine hydrochloride is widely used as an effective antimicrobial agent in medical, pharmaceutical, dental, and personal care applications due to its broad-spectrum activity and prolonged residual effect.
Chlorhexidine hydrochloride is commonly applied in skin antiseptics, surgical scrubs, and wound care products to reduce microbial contamination and prevent infection.

In oral care, Chlorhexidine hydrochloride is a key ingredient in mouthwashes and dental gels for the management of plaque, gingivitis, and oral infections.
Chlorhexidine hydrochloride is also utilized in hospital disinfectants, topical pharmaceutical formulations, personal hygiene products, and veterinary antiseptics, where reliable and sustained antimicrobial performance is required.

Medical antiseptics:
Chlorhexidine hydrochloride is used in skin disinfectants, preoperative antiseptics, and surgical scrubs to reduce microbial load and prevent infections.

Wound care:
Chlorhexidine hydrochloride is applied in wound cleansing solutions, dressings, and topical preparations to control bacterial contamination.

Oral care products:
Chlorhexidine hydrochloride is used in mouthwashes, dental gels, and rinses for the prevention and treatment of gingivitis, plaque, and oral infections.

Hospital and clinical disinfection:
Chlorhexidine hydrochloride is incorporated into disinfectants for medical instruments, hospital surfaces, and healthcare environments.

Pharmaceutical formulations:
Chlorhexidine hydrochloride is used as an active ingredient or preservative in topical pharmaceutical products.

Personal hygiene products:
Chlorhexidine hydrochloride is included in soaps, hand washes, and antiseptic cleansers for personal and professional hygiene.

Veterinary applications:
Chlorhexidine hydrochloride is used in veterinary antiseptics for skin, wound, and oral care in animals.

Industrial and laboratory use:
Chlorhexidine hydrochloride is used in laboratories and industrial settings where controlled antimicrobial activity is required.

Features of Chlorhexidine Hydrochloride:

Broad-spectrum antimicrobial activity:
Chlorhexidine hydrochloride exhibits activity against Gram-positive and Gram-negative bacteria, as well as fungi and enveloped viruses.

Strong cationic character:
Chlorhexidine hydrochloride binds to negatively charged microbial cell membranes, leading to membrane disruption and cell death.

High substantivity:
Chlorhexidine hydrochloride adsorbs to skin, mucous membranes, and dental surfaces, providing prolonged antimicrobial action.

Enhanced solubility and stability:
Chlorhexidine hydrochloride is supplied as the hydrochloride salt to improve water solubility and formulation stability.

Low systemic absorption:
Chlorhexidine hydrochloride primarily acts locally with minimal absorption through intact skin and mucosa when used as directed.

Rapid and persistent action:
Chlorhexidine hydrochloride provides immediate antimicrobial effects with sustained residual activity.

Wide formulation compatibility:
Chlorhexidine hydrochloride is suitable for pharmaceutical, medical, dental, and personal care formulations.

Established safety profile:
Chlorhexidine hydrochloride has a well-documented safety record supported by extensive clinical and regulatory use.

Occurrence of Chlorhexidine Hydrochloride:
Chlorhexidine hydrochloride does not occur naturally in the environment and is a fully synthetic compound produced exclusively through industrial chemical synthesis.
Chlorhexidine hydrochloride is not found in plants, animals, or natural biological systems.

Chlorhexidine hydrochloride is encountered only in manufactured products and controlled settings, such as pharmaceutical formulations, medical antiseptics, dental products, personal hygiene items, veterinary preparations, and hospital disinfectants.
Chlorhexidine hydrochloride's presence in the environment is therefore limited and typically associated with intentional use in healthcare, industrial, or laboratory applications rather than natural occurrence.

Synthesis of Chlorhexidine Hydrochloride:
Chlorhexidine hydrochloride is synthesized through a multi-step chemical process involving the formation of the chlorhexidine base followed by salt formation with hydrochloric acid.
Initially, p-chlorophenyl biguanide intermediates are produced by the reaction of p-chloroaniline derivatives with dicyandiamide under controlled conditions.

These intermediates are then coupled with hexamethylene diamine, resulting in the formation of the chlorhexidine free base, a bisbiguanide compound.
In the final step, the chlorhexidine base is reacted with hydrochloric acid to form Chlorhexidine hydrochloride, which improves water solubility and stability.
The product is subsequently purified, crystallized, and dried to obtain pharmaceutical-grade material suitable for medical, dental, and personal care applications.

Stability and Reactivity of Chlorhexidine Hydrochloride:

Chemical Stability:
Chlorhexidine hydrochloride is chemically stable under normal ambient temperatures and recommended conditions of use and storage.
Chlorhexidine hydrochloride does not undergo hazardous decomposition during routine handling when protected from moisture, heat, and light.

Reactivity:
The material is generally non-reactive under normal conditions.
However, Chlorhexidine hydrochloride may degrade or lose efficacy in the presence of strong oxidizing agents, strong acids, or strong bases.

Conditions to Avoid:
Avoid excessive heat, prolonged exposure to moisture, and direct sunlight.
Avoid conditions that may promote chemical degradation or hydrolysis.

Incompatible Materials:
Avoid contact with strong oxidizing agents, strong acids, strong bases, anionic surfactants, and soaps, as these may reduce antimicrobial activity or cause decomposition.

Hazardous Decomposition Products:
Thermal decomposition or combustion may produce nitrogen oxides, hydrogen chloride, and carbon oxides.

Handling and Storage of Chlorhexidine Hydrochloride:

Safe Handling:
Handle Chlorhexidine hydrochloride in well-ventilated areas to minimize dust exposure.
Avoid inhalation of dust and avoid contact with skin and eyes.
Use controlled dispensing methods to reduce airborne particles.

Hygiene Measures:
Wash hands and exposed skin thoroughly after handling.
Avoid eating, drinking, or smoking in handling areas.
Remove contaminated clothing before reuse.

Storage Requirements:
Store in tightly closed containers in a cool, dry, and well-ventilated environment.
Protect from moisture and direct light.

Packaging Integrity:
Keep containers tightly sealed when not in use to maintain product quality and prevent contamination.

Shelf Stability:
Chlorhexidine hydrochloride maintains stability for extended periods when stored under recommended conditions.

First Aid Measures of Chlorhexidine Hydrochloride:

Inhalation:
Move the exposed person to fresh air immediately.
If respiratory irritation, coughing, or discomfort persists, seek medical attention.

Skin Contact:
Wash skin thoroughly with soap and water.
Remove contaminated clothing.
Seek medical attention if irritation or allergic reaction develops.

Eye Contact:
Rinse eyes cautiously with clean water for several minutes while holding eyelids open.
Remove contact lenses if present and easy to do.
Seek medical attention if irritation persists.

Ingestion:
Rinse mouth with water.
Do not induce vomiting.
Seek immediate medical attention.

Notes for Physician:
Treat symptomatically.
No specific antidote is available.

Firefighting Measures of Chlorhexidine Hydrochloride:

Flammability:
Chlorhexidine hydrochloride is not flammable and does not support combustion.

Suitable Extinguishing Media:
Use extinguishing media appropriate for surrounding materials, such as water spray, foam, dry chemical powder, or carbon dioxide (CO₂).

Hazardous Combustion Products:
Combustion may release toxic gases including nitrogen oxides and hydrogen chloride.

Special Protective Equipment for Firefighters:
Wear self-contained breathing apparatus and full protective clothing when fighting fires involving surrounding materials.

Specific Hazards:
Avoid inhalation of combustion products and dust generated during firefighting operations.

Accidental Release Measures of Chlorhexidine Hydrochloride:

Personal Precautions:
Avoid dust generation and inhalation.
Use appropriate personal protective equipment.
Ensure adequate ventilation.

Environmental Precautions:
Prevent large quantities from entering drains, surface water, or soil.
The product is not expected to pose significant environmental hazards under normal conditions.

Cleanup Methods:
Collect spilled material using sweeping, vacuuming with HEPA filters, or damp methods to minimize dust formation.
Place material into suitable containers for disposal according to local regulations.

Additional Advice:
Clean contaminated surfaces with water after material collection to remove residues.

Exposure Controls / Personal Protective Equipment of Chlorhexidine Hydrochloride:

Engineering Controls:
Provide adequate general or local exhaust ventilation, particularly in areas where dust may be generated.

Respiratory Protection:
Use a particulate respirator (e.g., N95 or equivalent) if dust levels exceed recommended exposure limits.

Hand Protection:
Wear protective gloves such as nitrile or latex to prevent skin contact during prolonged handling.

Eye Protection:
Wear safety glasses or goggles to protect against dust or accidental splashes.

Skin and Body Protection:
Use appropriate protective clothing to minimize skin exposure.

Environmental Exposure Controls:
No special environmental control measures are required beyond standard dust containment and waste management practices.

Identifiers of Chlorhexidine Hydrochloride:
Chemical family: Bisbiguanide antimicrobial
CAS number: 3697-42-5
EC / EINECS number: 222-018-2
Molecular formula: C₂₂H₃₀Cl₂N₁₀ · 2HCl
Molecular weight: Approximately 578.4 g/mol
Physical state: Solid
Appearance: White to off-white crystalline powder
Odor: Odorless or faint characteristic odor

Solubility:
Soluble in water and alcohol
Insoluble in non-polar organic solvents
pH (aqueous solution): Slightly acidic

Empirical Formula (Hill Notation): C22H30Cl2N10 · 2HCl
CAS Number: 3697-42-5
Molecular Weight: 578.37
NACRES: NA.24
PubChem Substance ID: 329823393
UNSPSC Code: 41116107
EC Number: 223-026-6
MDL number: MFCD00068998

SMILES Code: C1=CC(=CC=C1NC(=NC(=NCCCCCCN=C(N)N=C(N)NC2=CC=C(C=C2)Cl)N)N)Cl.Cl.Cl
Molecular Weight: 578.37
Formula: C22H30Cl2N10.2HCl
Purity: 98.25

Properties of Chlorhexidine Hydrochloride:
Physical state: Solid
Appearance: White to off-white crystalline powder
Odor: Odorless or faint characteristic odor
Molecular formula: C₂₂H₃₀Cl₂N₁₀ · 2HCl
Molecular weight: Approximately 578.4 g/mol

Melting point: ~132–136 °C (decomposes)
Boiling point: Not applicable (decomposes)
Vapor pressure: Negligible
Solubility in water: Freely soluble
Solubility in alcohol: Soluble
Solubility in non-polar solvents: Practically insoluble

InChI key: WJLVQTJZDCGNJN-UHFFFAOYSA-N
InChI: 1S/C22H30Cl2N10.2ClH/c23-15-5-9-17(10-6-15)31-21(27)33-19(25)29-13-3-1-2-4-14-30-20(26)34-22(28)32-18-11-7-16(24)8-12-18;;/h5-12H,1-4,13-14H2,(H5,25,27,29,31,33)(H5,26,28,30,32,34);2*1H
SMILES string: Cl.Clc1ccc(NC(=N)NC(=N)NCCCCCCNC(=N)NC(=N)Nc2ccc(Cl)cc2)cc1
API family: chlorhexidine
CofA: current certificate can be downloaded
application(s): pharmaceutical (small molecule)
format: neat
storage temp.: 2-8°C
Quality Level: 300

Molecular Weight: 578.4 g/mol
Hydrogen Bond Donor Count: 8
Hydrogen Bond Acceptor Count: 2
Rotatable Bond Count: 13
Exact Mass: 578.153602 Da
Monoisotopic Mass: 576.156552 Da
Topological Polar Surface Area: 178 Ų
Heavy Atom Count: 36
Complexity: 648
Isotope Atom Count: 0
Defined Atom Stereocenter Count: 0
Undefined Atom Stereocenter Count: 0
Defined Bond Stereocenter Count: 2
Undefined Bond Stereocenter Count: 0
Covalently-Bonded Unit Count: 3
Compound Is Canonicalized: Yes

Appearance: White to off-white crystalline powder
Odor: Odorless or faint characteristic odor
Taste: Bitter (notable in oral formulations)
Chemical type: Cationic bisbiguanide compound
Physical form: Solid (hydrochloride salt)