Diclofenac sodium
[CAS# 15307-79-6]

Identification

• Classification: API >> Antipyretic analgesics >> Non-steroidal anti-inflammatory drugs
• Name: Diclofenac sodium
• Synonyms: 2-[(2,6-Dichlorophenyl)amino]benzeneacetic acid sodium salt
• Molecular Formula: C₁₄H₁₀Cl₂NNaO₂
• Molecular Weight: 318.13
• CAS Registry Number: 15307-79-6
• EC Number: 239-346-4
• SMILES: C1=CC=C(C(=C1)CC(=O)[O-])NC2=C(C=CC=C2Cl)Cl.[Na+]

Properties

• Melting point: 275 - 277 ºC (Expl.)
• Solubility: Soluble 50 mM (water), 100 mM (DMSO) (Expl.)

Safety Data

• Hazard Symbols: GHS06;GHS07;GHS08;GHS09 Danger
• Hazard Statements: H301-H315-H319-H331-H361-H372-H411
• Precautionary Statements: P203-P260-P261-P264-P264+P265-P270-P271-P273-P280-P301+P316-P302+P352-P304+P340-P305+P351+P338-P316-P318-P319-P321-P330-P332+P317-P337+P317-P362+P364-P391-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Acute toxicity	Acute Tox.	3	H301
Reproductive toxicity	Repr.	2	H361
Specific target organ toxicity - repeated exposure	STOT RE	1	H372
Chronic hazardous to the aquatic environment	Aquatic Chronic	2	H411
Acute toxicity	Acute Tox.	3	H331
Skin irritation	Skin Irrit.	2	H315
Eye irritation	Eye Irrit.	2	H319
Reproductive toxicity	Repr.	2	H361d
Chronic hazardous to the aquatic environment	Aquatic Chronic	3	H412
Acute toxicity	Acute Tox.	4	H302
Reproductive toxicity	Lact.	-	H362
Specific target organ toxicity - repeated exposure	STOT RE	2	H373
Acute toxicity	Acute Tox.	3	H311
Acute toxicity	Acute Tox.	2	H310
Reproductive toxicity	Repr.	1B	H360
Acute toxicity	Acute Tox.	2	H330
Specific target organ toxicity - single exposure	STOT SE	3	H335
Chronic hazardous to the aquatic environment	Aquatic Chronic	3	H413
Specific target organ toxicity - single exposure	STOT SE	1	H370
Acute toxicity	Acute Tox.	4	H332

• Transport Information: UN 2811

Discovory and Applicatios

Diclofenac sodium is the sodium salt of diclofenac, a nonsteroidal anti-inflammatory drug (NSAID) widely used for its analgesic, anti-inflammatory, and antipyretic effects. Chemically, diclofenac is a substituted phenylacetic acid derivative, and its sodium salt is more soluble in water, facilitating oral and parenteral formulations. The compound is characterized by the presence of two aromatic rings connected by a nitrogen atom and a carboxymethyl group, contributing to its pharmacological activity and physicochemical behavior.

The synthesis and pharmacological evaluation of diclofenac began in the 1960s. It was developed by Ciba-Geigy (now part of Novartis) and introduced to the market in the 1970s as a potent NSAID. Diclofenac sodium quickly gained widespread clinical acceptance due to its broad efficacy in treating inflammation, pain, and fever associated with a variety of conditions, including rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, acute musculoskeletal injuries, and dysmenorrhea. Over the years, diclofenac sodium has become one of the most commonly prescribed NSAIDs globally.

The primary mechanism of action of diclofenac sodium is the inhibition of cyclooxygenase (COX) enzymes, particularly COX-2, which reduces the synthesis of prostaglandins responsible for pain, inflammation, and fever. Diclofenac shows some selectivity for COX-2 over COX-1, which may result in fewer gastrointestinal side effects compared to traditional non-selective NSAIDs, although such effects are still possible. The sodium salt form offers rapid dissolution and absorption when administered orally, resulting in a relatively fast onset of action.

Diclofenac sodium is available in multiple pharmaceutical formulations to suit various clinical needs. Oral dosage forms include immediate-release tablets, enteric-coated tablets, and extended-release tablets or capsules. Parenteral forms, such as intramuscular injections, are used for acute pain management in clinical settings. Topical gels and transdermal patches are also widely used, allowing localized delivery of the drug with minimal systemic exposure. Additionally, suppositories and ophthalmic solutions have been developed for specific therapeutic uses.

The pharmacokinetics of diclofenac sodium include high plasma protein binding, extensive hepatic metabolism primarily by cytochrome P450 enzymes (notably CYP2C9), and elimination through urine and bile. Its relatively short half-life necessitates multiple daily doses for sustained effect in conventional oral formulations, although extended-release versions are available to reduce dosing frequency.

Beyond pain and inflammation control, diclofenac sodium has been used in the management of postoperative pain, migraine, renal colic, and certain soft tissue disorders. In ophthalmology, diclofenac sodium eye drops are used to control inflammation following cataract surgery or corneal refractive procedures.

The safety profile of diclofenac sodium is similar to that of other NSAIDs, with common adverse effects including gastrointestinal irritation, nausea, dyspepsia, and, at higher doses or prolonged use, the potential for ulceration or gastrointestinal bleeding. Cardiovascular risks associated with NSAIDs, particularly with long-term use or in patients with predisposing factors, are also a consideration. Renal and hepatic adverse effects, though less frequent, are documented and necessitate appropriate monitoring in certain populations.

In veterinary medicine, diclofenac sodium has been used in some species, but its use is restricted or avoided in others due to toxicity concerns. For example, diclofenac has been linked to vulture population declines in parts of Asia due to renal failure following ingestion of treated livestock carcasses, leading to regulatory bans in veterinary contexts in certain regions.

In summary, diclofenac sodium is a widely used nonsteroidal anti-inflammatory drug with broad clinical applications in pain and inflammation management. Its effectiveness, availability in various formulations, and long history of use have made it a cornerstone in both acute and chronic treatment regimens. Despite its efficacy, careful attention to dosing and monitoring is required to minimize the risk of adverse effects.

References

1979. A comparison of the carrageenan edema test and ultraviolet light-induced erythema test as predictors of the clinical dose in rheumatoid arthritis. Inflammation Research.
DOI: 10.1007/bf01968133

1994. The efficacy and relative bioavailability of diclofenac resinate in rheumatoid arthritis patients. International journal of clinical pharmacology and therapeutics.
URL: https://pubmed.ncbi.nlm.nih.gov/7981929

1994. Metabolic Activation and Immunochemical Localization of Liver Protein Adducts of the Nonsteroidal Anti-inflammatory Drug Diclofenac. Chemical Research in Toxicology, 7(4).
DOI: 10.1021/tx00040a014