Azelaic acid is also known as nonanedioic acid. It is a naturally occurring saturated dicarboxylic acid found in small amounts in grains such as wheat, rye and barley. Azelaic acid is widely used in dermatological and cosmetic formulations, particularly in products intended for blemish-prone, redness-prone and uneven-toned skin.

Chemical Information

Azelaic acid is a straight-chain, saturated dicarboxylic acid containing nine carbon atoms. Its molecular formula is C9H16O4 and its molecular weight is 188.22 g/mol. It contains two carboxylic acid groups and behaves as a weak acid in aqueous systems.

INCI Name: Azelaic Acid
Other Name: Nonanedioic Acid
CAS Number: 123-99-9
Chemical Class: Dicarboxylic Acid
Molecular Formula: C9H16O4
Molecular Weight: 188.22 g/mol

Function

Azelaic acid is associated with antimicrobial, anti-inflammatory, keratinization-modulating, antimelanogenic and antioxidant activities. In cosmetic formulations, it is primarily used in products targeting blemish-prone skin, uneven skin tone, redness and the appearance of post-inflammatory hyperpigmentation.

Cosmetic Applications

Azelaic acid can be incorporated into skincare formulations intended for blemish-prone skin, uneven skin tone, redness-prone skin and products targeting the appearance of post-inflammatory hyperpigmentation. It may be used in creams, gels, lotions and other topical formulations.

Azelaic acid is particularly well known for its use in dermatological products for acne vulgaris and papulopustular rosacea. Research has also investigated its application in hyperpigmentation and melasma.

How Azelaic Acid Works

Azelaic acid has several biological activities that are relevant to skin care and dermatological applications.

It has antimicrobial activity against microorganisms associated with acne, including Cutibacterium acnes and Staphylococcus epidermidis. Its antimicrobial effects are considered one of the mechanisms contributing to its use in acne treatment.

Azelaic acid also influences keratinization within the follicle. By modulating abnormal keratinization, it can help reduce processes associated with the formation of comedones and clogged pores.

The ingredient also demonstrates anti-inflammatory activity. Research suggests that azelaic acid can influence inflammatory pathways and reduce oxidative stress, including the production of reactive oxygen species by neutrophils.

Azelaic acid has also been studied for its effects on melanogenesis. It can inhibit tyrosinase activity and preferentially affect abnormal or highly active melanocytes, which contributes to its use in formulations and dermatological treatments targeting hyperpigmentation.

The mechanisms responsible for the effects of azelaic acid in rosacea are complex and are not completely understood.

Formulation Considerations

Azelaic acid has relatively low solubility in water, which can present formulation challenges. Depending on the formulation system, it may be incorporated through appropriate dispersion, solvent or solubilization strategies.

Particle size and dispersion quality are important considerations when formulating products containing azelaic acid. Poor dispersion can result in an uneven texture, grittiness or reduced sensory quality in the finished product.

The choice of vehicle and supporting formulation components can significantly affect the performance and sensory characteristics of an azelaic acid product. Rheology modifiers, emollients, emulsifiers and solvents should therefore be selected according to the intended dosage form and formulation requirements.

Because azelaic acid is commonly used at relatively high concentrations in some dermatological preparations, achieving a homogeneous and cosmetically elegant formulation can require careful development and optimization.

Recommended Use

The appropriate concentration of azelaic acid depends on the intended product type, regulatory classification, target market, formulation system and intended claims.

Dermatological products commonly contain concentrations such as 15% or 20%, while cosmetic formulations may use different concentrations depending on the intended application and applicable regulations.

The concentration and claims of a cosmetic product should always be assessed in accordance with the regulatory requirements of the target market.

Skin Compatibility

Azelaic acid is generally well tolerated when appropriately formulated. However, topical application may cause temporary sensations such as stinging, burning, itching, dryness or irritation, particularly when higher concentrations are used or when the ingredient is first introduced.

The tolerability of azelaic acid can be influenced by concentration, formulation vehicle, pH and the presence of other potentially irritating active ingredients.

Stability

Azelaic acid itself is considered a relatively stable molecule, although the stability of a finished formulation depends on the complete formulation system.

Important factors include pH, temperature, particle size, dispersion quality, solvent system, packaging and interactions with other ingredients.

Finished products containing azelaic acid should undergo appropriate stability testing to evaluate changes in appearance, color, odor, pH, viscosity, texture, physical integrity and other relevant quality characteristics throughout the intended shelf life.

Safety

Azelaic acid has been extensively evaluated in dermatological applications and is generally considered to have a favorable topical safety profile.

Clinical studies of topical azelaic acid commonly report local adverse effects such as mild and transient stinging, burning, itching, dryness or irritation. These effects are generally localized and tend to decrease with continued use.

Historical toxicological data report an acute oral LD50 greater than 5,000 mg/kg in rats. Older experimental studies have also reported mild irritation in certain rabbit skin and eye tests.

Animal toxicology data should be interpreted in the context of the specific experimental conditions and should not be directly equated with the safety of a finished cosmetic product. The safety of a finished formulation depends on factors including concentration, exposure route, frequency of use, formulation matrix, intended application and target population.

Regulatory Considerations

Azelaic acid is used in both cosmetic and medicinal products, and its regulatory status may differ between jurisdictions depending on the product category, concentration and claims.

When developing a cosmetic product containing azelaic acid, the applicable legislation in the target market should be reviewed before determining the formulation, concentration and product claims.

The regulatory assessment should distinguish between cosmetic and medicinal use, particularly where claims relate to the treatment or prevention of a disease or medical condition.

Scientific Background

Azelaic acid has been extensively studied in dermatology. Research has demonstrated antimicrobial, anti-inflammatory, keratinization-modulating and antimelanogenic activities.

A 2024 review described azelaic acid as a saturated dicarboxylic acid with antibacterial, anti-keratinizing, antimelanogenic, antioxidant and anti-inflammatory properties. The review also discussed mechanisms involving inflammatory signaling, microbial activity, keratinization and melanogenesis.

Clinical research and systematic reviews have reported evidence supporting the topical use of azelaic acid for acne and rosacea, while additional research has investigated its potential role in the management of hyperpigmentation and melasma.

References

Dweck, Anthony. Handbook of Natural Ingredients. Dweck Books.

Feng, X., Shang, J., Gu, Z., Gong, J., Chen, Y., and Liu, Y. “Azelaic Acid: Mechanisms of Action and Clinical Applications.” Clinical, Cosmetic and Investigational Dermatology, 2024. DOI: 10.2147/CCID.S485237.

King, S., Campbell, J., Rowe, R., Daly, M.-L., Moncrieff, G., and Maybury, C. “A systematic review to evaluate the efficacy of azelaic acid in the management of acne, rosacea, melasma and skin aging.” Journal of Cosmetic Dermatology, 2023. DOI: 10.1111/jocd.15923.

U.S. Food and Drug Administration. Azelex (azelaic acid) Cream 20% Prescribing Information.

National Center for Biotechnology Information. PubChem – Azelaic Acid.

National Center for Biotechnology Information. PubMed – Azelaic Acid.

Jones, D. A. “Rosacea, Reactive Oxygen Species, and Azelaic Acid.” The Journal of Clinical and Aesthetic Dermatology, 2009.

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