CHLORHEXIDINE HCL

Chlorhexidine HCl is the hydrochloride salt of chlorhexidine, a cationic bisbiguanide compound used as a broad-spectrum topical antiseptic with sustained antimicrobial efficacy.
Chlorhexidine HCl inhibits microbial growth by electrostatically interacting with negatively charged bacterial membranes, increasing membrane permeability and leading to cytoplasmic leakage and protein coagulation at elevated concentrations.
Chlorhexidine HCl's strong surface binding, stability under normal storage conditions, and compatibility with diverse formulations make it a standard antimicrobial component in healthcare, dental, and pharmaceutical applications.

CAS Number: 3697-42-5
EC Number: 223-026-6
Molecular Formula: C22H32Cl4N10
Molecular Weight: 578.37

Synonyms: Chlorhexidine oral antiseptic, Chlorhexidine skin antiseptic, Chlorhexidine medical antiseptic, Chlorhexidine antimicrobial compound, Chlorhexidine bactericidal agent, Chlorhexidine fungicidal agent, Chlorhexidine bisbiguanide, Chlorhexidine hydrochloride USP, Chlorhexidine hydrochloride BP, Chlorhexidine hydrochloride EP, CHX hydrochloride, Chlorhexidine HCl salt, Chlorhexidine antiseptic hydrochloride, Chlorhexidine cationic biguanide, Bisbiguanide hydrochloride antiseptic, , 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, 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, CHEBI:31393, HY-B1145R, HMS1920M21, (1E)-2-[6-[[amino-[(E)-[amino-(4-chloroanilino)methylidene]amino]methylidene]amino]hexyl]-1-[amino-(4-chloroanilino)methylidene]guanidine;dihydrochloride, HY-B1145, Tox21_302689, 1,1'-Hexamethylene bis(5-(p-chlorophenyl)biguanide), dihydrochloride, CCG-38942, s3067, AKOS015895378, Chlorhexidine dihydrochloride, >=98%, AC-4684, CS-4749, EBC-147030, KS-5084, NSC 756679, Chlorhexidine hydrochloride (JP17/USP), CHLORHEXIDINE HYDROCHLORIDE [JAN], NCGC00094621-01, NCGC00094621-02, NCGC00256637-01, 2,4,11,13-Tetraazatetradecanediimidamide, N,N'-bis(4-chlorophenyl)-3,12-diimino-, dihydrochloride, CHLORHEXIDINE DIHYDROCHLORIDE [MI], CHLORHEXIDINE HYDROCHLORIDE [USAN], CAS-3697-42-5, Chlorhexidine (dihydrochloride) (Standard), CHLORHEXIDINE HYDROCHLORIDE [MART.], CHLORHEXIDINE HYDROCHLORIDE [WHO-DD], CHLORHEXIDINE DIHYDROCHLORIDE [WHO-IP], CHLORHEXIDINE HYDROCHLORIDE [GREEN BOOK], D01345, 697C425, CHLORHEXIDINE HYDROCHLORIDE [USP IMPURITY], CHLORHEXIDINE HYDROCHLORIDE [USP MONOGRAPH], CHLORHEXIDINE DIHYDROCHLORIDE [EP MONOGRAPH], 1,1'-HEXAMETHYLENEBIS(5-(P-CHLOROPHENYL)BIGUANIDE)DIHYDROCHLORIDE, 2,4,11,13-TEtraazatetradecanamide,14-[(4-chlorophenyl)amino]-3,12,14-triimino, Chlorhexidine dihydrochloride, European Pharmacopoeia (EP) Reference Standard, Chlorhexidine Hydrochloride, Pharmaceutical Secondary Standard; Certified Reference Material, N-(4-chlorophenyl)-1-3-(6-{N-[3-(4-chlorophenyl)carbamimidamidomethanimidoyl]amino}hexyl)carbamimidamidomethanimidamide dihydrochloride

Chlorhexidine HCl is a bisbiguanide-based synthetic antimicrobial agent that is primarily used as a topical antiseptic because of its reliable and long-lasting activity.
In Chlorhexidine hydrochloride salt form, chlorhexidine shows improved suitability for pharmaceutical processing and formulation compared with the free base.

Chlorhexidine HCl demonstrates strong inhibitory effects against a broad range of Gram-positive and Gram-negative bacteria as well as yeasts, while exhibiting weak activity toward mycobacteria and no effectiveness against bacterial spores.
The antimicrobial effect originates from Chlorhexidine HCl's cationic structure, which enables strong attraction to negatively charged microbial cell membranes, leading to membrane destabilization, increased permeability, and loss of essential intracellular materials; at higher concentrations, this process results in irreversible protein coagulation and cell death.

One of the most notable features of Chlorhexidine HCl is its residual antimicrobial action. 
Once applied, Chlorhexidine HCl readily binds to skin and mucosal surfaces and remains attached, from where it is gradually released, ensuring prolonged protection against microbial growth.

Chlorhexidine HCl is chemically stable under normal storage conditions and retains activity across a wide pH range, although interactions with organic matter or anionic surfactants can reduce its effectiveness.
Because of its persistent antimicrobial behavior, formulation flexibility, and consistent performance, Chlorhexidine HCl is extensively incorporated into medical, dental, pharmaceutical, and veterinary products, particularly those designed for topical antisepsis, oral hygiene, and infection prevention.

Chlorhexidine HCl is a broad-spectrum cationic surfactant known for its powerful antibacterial and disinfectant properties.
Chlorhexidine HCl's core function is to kill bacteria and provide effective disinfection, making it a vital ingredient in both medical and daily-use products.
With high safety and excellent stability, Chlorhexidine HCl has become a trusted antimicrobial agent in pharmaceuticals, personal care, and healthcare applications.

Pharmaceutical secondary standards for application in quality control, provide pharma laboratories and manufacturers with a convenient and cost-effective alternative to the preparation of in-house working standards.

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

Chlorhexidine HCl 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 HCl into human albumin microspheres.
This lengthened antibacterial activity against Escheria coli, Staphylococcus aureus and Pseudomonas aeruginosa.

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

Chlorhexidine HCl 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 HCl is gradually colored by light.

Chlorhexidine is a broad-spectrum antimicrobial biguanide used as a topical antiseptic and in dental practice for the treatment of inflammatory dental conditions caused by microorganisms.
Chlorhexidine HCl is one of the most common skin and mucous membrane antiseptic agents in use today.

The molecule itself is a cationic bis-guanide consisting of two 4-chlorophenyl rings and two biguanide groups joined by a central hexamethylene chain.
Topical chlorhexidine for disinfection, as well as oral rinses for dental use, carries activity against a broad range of pathogens including bacteria, yeasts, and viruses.

Chlorhexidine was developed in the UK by Imperial Chemical Industries in the early 1950s9 and was introduced to the US in the 1970s.
The FDA withdrew Chlorhexidine HCl's approval for the use of chlorhexidine gluconate topical tincture 0.5%, due to a significant number of reports concerning chemical and thermal burns associated with the use of this product.

Applications of Chlorhexidine HCl:
Chlorhexidine HCl may be used as a pharmaceutical reference standard for the determination of the analyte in ointment and pharmaceutical formulations by various chromatography techniques.
These Secondary Standards are qualified as Certified Reference Materials.
These are suitable for use in several analytical applications including but not limited to pharma release testing, pharma method development for qualitative and quantitative analyses, food and beverage quality control testing, and other calibration requirements.

Medical and Healthcare:
Chlorhexidine HCl is used in antiseptic solutions, wound disinfectants, and surgical scrubs.
Effective against bacteria, fungi, and some viruses, making it essential for hospitals, clinics, and dental care.

Daily Chemicals:
Incorporated in mouthwashes, hand sanitizers, and skin disinfectants.
Chlorhexidine HCl ensures safe and long-lasting antimicrobial effects in personal care products.

Pharmaceutical Industry:
Chlorhexidine HCl acts as a preservative in topical formulations, ophthalmic solutions, and medical devices.
Chlorhexidine HCl helps maintain product safety by preventing microbial contamination during storage and use.

Uses of Chlorhexidine HCl:
Chlorhexidine HCl is widely used as an effective antiseptic and antimicrobial agent in medical, dental, pharmaceutical, and veterinary applications due to its broad-spectrum activity and prolonged residual effect.

Medical and clinical use:
Chlorhexidine HCl is used for skin antisepsis prior to injections, catheter insertion, and minor surgical procedures to reduce the risk of microbial contamination and infection.
Chlorhexidine HCl is also applied in wound cleansing and general topical disinfection.

Dental and oral care:
Chlorhexidine HCl is incorporated into mouthwashes, gels, and topical oral formulations for the management of gingivitis, periodontal disease, and oral infections.
Chlorhexidine HCl is commonly used following dental procedures and oral surgery to control microbial growth in the oral cavity.

Pharmaceutical formulations:
Chlorhexidine HCl is used as an active antimicrobial ingredient in topical creams, ointments, sprays, and solutions.
Chlorhexidine HCl may also be used as a preservative or antimicrobial agent in certain pharmaceutical and healthcare products.

Veterinary applications:
Chlorhexidine HCl is used for skin disinfection, wound care, and surgical preparation in animals, as well as in veterinary hygiene and infection control products.

Laboratory and industrial hygiene:
Chlorhexidine HCl is used for surface disinfection and equipment sanitation in laboratory, clinical, and controlled environments where effective microbial control is required.

Features of Chlorhexidine HCl:

Broad-spectrum antimicrobial:
Effective against Gram-positive and Gram-negative bacteria.

High safety profile:
Suitable for both human and medical use.

Stable and reliable:
Maintains activity over a wide range of formulations.

Versatile applications:
Chlorhexidine HCl is used in medicine, daily chemicals, and healthcare products.

Easy to formulate:
Compatible with water-based systems.

Pharmacodynamics of Chlorhexidine HCl:
Chlorhexidine is a broad-spectrum antimicrobial with demonstrated activity against both gram-positive and gram-negative bacteria, yeasts, and viruses.
Antimicrobial activity is dose-dependent - chlorhexidine is bacteriostatic at lower concentrations (0.02%-0.06%) and bactericidal at higher concentrations (>0.12%).

Pharmacokinetic studies of oral chlorhexidine rinses indicate that approximately 30% of the active ingredient is retained in the mouth following rinsing, which is subsequently slowly released into oral fluids.
This ability to adsorb to dentine, shared with tetracycline antibiotics such as doxycycline, is known as "substantivity" and is the result of chlorhexidine's positive charge - it is likely that this substantivity plays at least some role in chlorhexidine's antimicrobial activity, as its persistence on surfaces such as dentine prevent microbial colonization.7

Dental chlorhexidine rinses may result in staining of oral surfaces, such as teeth.
This effect is not ubiquitous and appears to be more significant with extended therapy (i.e. up to 6 months) - nevertheless, patients for whom oral staining is unacceptable should use chlorhexidine rinse with caution and for the shortest effective interval.
Allergic reactions to chlorhexidine have been associated with the development of anaphylaxis.

Action Mechanism of Chlorhexidine HCl:
Chlorhexidine’s broad-spectrum antimicrobial effects are due to its ability to disrupt microbial cell membranes.
The positively charged chlorhexidine molecule reacts with negatively charged phosphate groups on microbial cell surfaces - this reaction both destroys the integrity of the cell, allowing leakage of intracellular material, and allows chlorhexidine to enter the cell, causing precipitation of cytoplasmic components and ultimately cell death.
The specific means of cell death is dependent on the concentration of chlorhexidine - lower concentrations are bacteriostatic and result in leakage of intracellular substances such as potassium and phosphorous, whereas higher concentrations are bactericidal and cause cytoplasmic precipitation.7

Synthesis of Chlorhexidine HCl:
Chlorhexidine HCl is synthesized by first preparing the chlorhexidine free base through a stepwise bisbiguanide formation, followed by conversion to the hydrochloride salt.
Industrially, the core structure is assembled by reacting a hexamethylene-bridged diamine intermediate with activated biguanide-forming reagents that carry the p-chlorophenyl substituents.

Under controlled temperature and solvent conditions, these reactions build two biguanide units on the same molecule, producing the characteristic cationic bisbiguanide framework.
After completion, the crude chlorhexidine base is isolated and purified to remove residual starting materials and side-products.

In the final step, the purified chlorhexidine base is treated with hydrochloric acid to form Chlorhexidine HCl.
This acid–base reaction yields the HCl salt, which typically precipitates or crystallizes depending on solvent system and concentration.

The solid is then recovered by filtration, washed to reduce soluble impurities, and dried under controlled conditions to achieve the required moisture level and purity.
Batch-to-batch consistency is ensured through quality control testing such as identity confirmation, assay/purity determination, residual solvent checks, and verification of microbiological performance appropriate to the intended pharmaceutical or antiseptic application.

Stability and Reactivity of Chlorhexidine HCl:

Chemical stability:
Chlorhexidine HCl is chemically stable under normal conditions of use, handling, and storage.

Reactivity:
No hazardous reactions are expected under normal conditions; however, antimicrobial activity may be reduced by interaction with anionic substances.

Conditions to avoid:
Excessive heat, prolonged exposure to light, and contact with incompatible materials.

Incompatible materials:
Anionic surfactants, soaps, detergents, strong oxidizing agents, and strong bases.

Hazardous decomposition products:
Thermal decomposition may produce nitrogen oxides (NOₓ), carbon monoxide (CO), and carbon dioxide (CO₂).

Handling and Storage of Chlorhexidine HCl:

Handling:
Handle in accordance with good industrial hygiene and safety practices.
Avoid contact with eyes and prolonged skin exposure, especially when handling concentrated material.

Storage:
Store in a cool, dry, well-ventilated area.
Keep containers tightly closed when not in use.

Storage conditions:
Protect from moisture, excessive heat, and direct sunlight.

Packaging materials:
Compatible, chemically resistant containers recommended.

Shelf life:
Stable for extended periods when stored under recommended conditions.

First Aid Measures of Chlorhexidine HCl:

Inhalation:
Remove person to fresh air.
If respiratory irritation or discomfort persists, seek medical attention.

Skin contact:
Wash skin thoroughly with soap and water.
Prolonged exposure may cause irritation.

Eye contact:
Rinse cautiously with water for several minutes.
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 medical advice if discomfort occurs.

Most important symptoms:
Eye irritation, skin irritation, and mild respiratory discomfort.

Firefighting Measures of Chlorhexidine HCl:

Suitable extinguishing media:
Water spray, foam, dry chemical powder, or carbon dioxide (CO₂).

Specific hazards:
Not flammable; decomposition under fire conditions may release irritating or toxic fumes.

Protective equipment for firefighters:
Self-contained breathing apparatus and full protective clothing.

Special precautions:
Cool exposed containers with water spray if safe to do so.

Accidental Release Measures of Chlorhexidine HCl:

Personal precautions:
Avoid contact with skin and eyes.
Ensure adequate ventilation.
Use appropriate personal protective equipment.

Environmental precautions:
Prevent large quantities from entering drains or watercourses.

Methods for cleanup:
Absorb liquid spills with inert absorbent material or collect solid material carefully.
Dispose of according to local regulations.

Exposure Controls / Personal Protection of Chlorhexidine HCl:

Occupational exposure limits:
Not established.

Engineering controls:
Adequate general ventilation recommended.

Personal protective equipment (PPE):

Respiratory protection:
Not normally required; use if aerosols or mists are generated.

Hand protection:
Protective gloves recommended when handling concentrates.

Eye protection:
Safety glasses or goggles recommended.

Skin protection:
Protective clothing as appropriate.

Hygiene measures:
Wash hands after handling; avoid eating or drinking in work areas.

Identifiers of Chlorhexidine HCl:
CAS number: 3697-42-5
EC / EINECS number: 222-171-5
Molecular formula: C22H30Cl2N10 · HCl
Molecular weight: Approximately 541.45 g/mol
INCI name: Chlorhexidine
UN transport classification: Not classified as hazardous for transport

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

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

CAS: 697-42-5
Purity: ≥98%
Molecular Formula: C22H32Cl4N10
Molecular Weight: 578.37
EINECS: 223-026-6
Storage Period: 1 year

Properties of Chlorhexidine HCl:
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