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Cetyl palmitate

Table of contents

Other Names

1-Hexadecyl hexadecanoateCetaceumCetinCetyl cetyrateHexadecanoic acid, hexadecyl esterHexadecanyl hexadecanoateHexadecyl hexadecanoateHexadecyl palmitaten-Hexadecanyl hexadecanoaten-Hexadecanyl palmitaten-Hexadecyl hexadecanoaten-Hexadecyl palmitatePalmatic acid n-hexadecyl esterPalmitic acid cetyl esterPalmitic acid palmityl esterPalmitic acid, hexadecyl esterPalmityl palmitateSpermacetiSpermaceti syntheticSpermwaxSynthetic spermacetiWE(16:0/16:0)

Synopsis

Cetyl Palmitate: A Comprehensive Reference

1. Identity and Chemical Characterization

1.1 Nomenclature and Identifiers

Hexadecyl hexadecanoate, also known as cetyl palmitate, is the ester derived from hexadecanoic acid and 1-hexadecanol. It is listed under a number of synonyms in chemical databases, including palmityl palmitate, n-hexadecyl palmitate, and palmitic acid hexadecyl ester. Its IUPAC name is hexadecyl hexadecanoate, with CAS Number 540-10-3, EINECS 208-736-6, COSING REF No. 74965, CHEBI:75584, ChEMBL2106073, ChemSpider 10427, and ECHA InfoCard 100.007.943. It is also commonly marketed under trade designations such as Crodamol CP, Cutina CP, Precifac ATO, Schercemol CP, Rewowax CG, and Starfol CP.

The chemical formula of cetyl palmitate is C₃₂H₆₄O₂, with CAS Number 540-10-3. Its molecular weight is 480.85 g/mol. The linear formula is CH₃(CH₂)₁₄CO₂(CH₂)₁₅CH₃, with synonyms including palmityl palmitate, hexadecyl hexadecanoate, and palmitic acid palmityl ester.

According to ChEBI, cetyl palmitate is a palmitate ester resulting from the formal condensation of palmitic acid with palmityl alcohol. Cetyl palmitate has a melting temperature range of 46–53 ºC, which makes it suitable for use in various formulations, particularly those that require solidification at room or body temperature.

1.2 Physical Properties

It appears as a white, waxy solid at room temperature and is insoluble in water but soluble in organic solvents. It is a long-chain fatty acid ester characterized by a highly ordered crystalline lattice, which contributes to its stability in lipid-based formulations. Straight chain esters, such as cetyl palmitate and cetostearyl stearate, which are solid at room temperature, are used to increase the viscosity of emulsions.

1.3 Natural Sources

This white waxy solid is the primary constituent of spermaceti, the once highly prized wax found in the skull of sperm whales. Historically derived as the primary constituent — comprising 65–95% — of spermaceti, the waxy substance from sperm whale heads, cetyl palmitate is now predominantly synthesized through esterification of plant- or animal-derived fatty acids and alcohols to comply with regulations banning whale products. Stony corals, which build the coral reefs, contain large amounts of cetyl palmitate wax in their tissues, which may function in part as an antifeedant.

While cetyl palmitate itself is a synthetic ester, its principal component, palmitic acid, can be found in both animal fats and vegetable fats. Palmitic acid constitutes 20–30% of most animal fats and is an essential constituent of most vegetable fats, particularly palm oil, where it comprises 35–45% of the fat content.

1.4 Production and Synthesis

Cetyl palmitate is an ester of palmitic acid, obtained via the reaction of cetyl alcohol and palmitic acid. Cetyl palmitate is obtained by esterification of fatty acids and fatty alcohol. Vegetable-derived grades are now the dominant commercial form; RSPO (Roundtable on Sustainable Palm Oil)-certified grades derived from palm feedstocks are produced by major oleochemical manufacturers. It is produced in USP/NF-grade purity to meet regulatory standards for drug delivery systems, ensuring compatibility with active pharmaceutical ingredients. Cetyl palmitate must comply with compendial standards such as those set by the European Pharmacopoeia (Ph.Eur.) and the United States Pharmacopeia (USP).

1.5 Common Commercial Forms

Cetyl palmitate comes in the form of white waxy flakes. In pharmaceutical and cosmetic commerce, it is also available as white to off-white powders or granules. Cetyl palmitate is a product of natural and biodegradable origin. In pharmaceutical contexts, it is available as certified reference materials meeting USP and secondary pharmaceutical standard specifications, as listed by MilliporeSigma (Sigma-Aldrich).

2. Historical and Traditional Use

2.1 Spermaceti in European Medicine (Medieval to 19th Century)

Spermaceti, a waxy substance derived from the head of the sperm whale, was first recorded in European medical literature around 1100 at the School of Salerno in southern Italy, where it was noted for its potential therapeutic properties. This early documentation marked the beginning of human awareness and utilization of the material, initially prized for its emollient qualities in pharmaceutical preparations.

By the late medieval period, records indicate its incorporation into treatments for ailments such as inflammation and respiratory issues, reflecting a growing trade in whale-derived products across Mediterranean ports. In medieval and early modern Europe, spermaceti found primary application in medicinal ointments and cosmetic formulations, valued for its smooth texture and stability. It was blended into salves for skin conditions, cold creams, and pomades, often appearing in apothecary recipes by the 15th century in England.

At the Harvard-associated apothecary collections, spermaceti is classified as a demulcent and emollient, and its medicinal usage included incorporation into many different kinds of lotions, as well as for the treatment of gonorrhea and catarrh. Spermaceti could be mixed with wax and olive oil to form cerates — a substance similar to ointment but harder and non-melting — which was applied as an adhesive in excoriations.

Spermaceti was used in medicine in England (15th century) and later in cosmetics, pharmacy, and also in candles. Spermaceti was used chiefly in ointments, cosmetic creams, fine wax candles, pomades, and textile finishing; later it was used for industrial lubricants.

2.2 Industrial and Commercial Whaling Era (17th–19th Centuries)

Spermaceti has been extracted by whalers since the 17th century for human use in cosmetics, textiles, and candles. Spermaceti had enormous commercial value during the 18th and 19th centuries. Beyond candles, spermaceti was used in ointments, cosmetic creams, pomades, textile finishing products, and industrial lubricants.

Cetyl palmitate not only functions as an emollient, but also contributes specific body and texture to the majority of cream and lotion products. It functions as a base for ointments, cerates, and emulsions. Spermaceti preparations also appeared in multiple national pharmacopeias of the 18th and 19th centuries as official pharmaceutical excipients, where they were codified for use as the base for cold cream and other medicated vehicles.

2.3 Transition to Synthetic Production and Regulatory History

The chemical structure of cetyl palmitate (synthetic spermaceti) is the same as whale spermaceti. Following international prohibitions on commercial whaling, and the listing of sperm whales under the Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES), synthetic cetyl palmitate derived from plant-based palmitic acid and fatty alcohols became the universal substitute in pharmaceutical and cosmetic formulations. The compound's chemical identity remained unchanged; only its origin shifted from marine mammals to terrestrial plant sources.

3. Chemistry, Key Constituents, and Physical Properties in Context

3.1 Structural Features

Cetyl palmitate is a wax ester synthesized from cetyl alcohol (C₁₆H₃₃OH) and palmitic acid (C₁₆H₃₂O₂). It belongs to the class of long-chain saturated wax esters. Both component moieties — the hexadecanol chain and the hexadecanoic acid chain — are fully saturated 16-carbon units, making cetyl palmitate a symmetric, highly ordered, and thermally stable molecule. This long-chain fatty acid ester is characterized by a highly ordered crystalline lattice, which contributes to its stability in lipid-based formulations.

3.2 Relationship to Palmitic Acid and Its Biological Role

The palmitic acid moiety (released upon hydrolysis) is physiologically significant. Palmitic acid can be processed into ceramides, diacylglycerols, triacylglycerols, or saturated glycolipids (such as lyso-phosphatidic acids, lysophosphatidylethanolamine, and phosphatidic acids), although how this affects stratum corneum lipid composition remains to be fully characterized. Palmitic acid can also be utilized for palmitoylation of skin-specific proteins, which affect the differentiation and cornification within the epidermis.

3.3 Polymorphic Behavior in Formulations

With respect to lipid polymorphism, a decrease in the ordered structure of NLC was observed with the increase of both oil and Q10 loadings, allowing therefore high accommodation for Q10 within the NLC. This polymorphic behavior — the ability to transition between more and less ordered crystalline states — is a key property exploited in pharmaceutical nanoparticle design. A more disordered lipid matrix provides greater "imperfections" in the crystal lattice that can accommodate drug molecules, increasing loading capacity.

4. Mechanisms of Action

4.1 Emollient and Skin Barrier Mechanism

In cosmetics, cetyl palmitate has an emollient function, as it is able to form a lipid film over the skin which reduces water loss from the stratum corneum. Its emollient properties contribute to skin hydration by forming a protective barrier that reduces moisture loss. This occlusive film mechanism is shared by other solid wax esters; it acts primarily by physical means — coating the stratum corneum surface to retard transepidermal water loss (TEWL) — rather than through receptor-mediated biological signaling.

The enhanced skin hydration effect of NLCs is because of the lipid nanoparticles' occlusive properties, resulting in improved drug penetration into skin. When cetyl palmitate is formulated as a nanoparticle matrix, this occlusive effect is extended to facilitating percutaneous delivery of encapsulated actives.

4.2 Emulsification and Rheological Mechanisms

Cetyl palmitate is characterized by a dry touch and its ability to improve the texture and stability of emulsions. It improves emulsion texture and stability and gives structure to cosmetic sticks. As a solid wax ester at room temperature, cetyl palmitate increases the internal phase viscosity and prevents droplet coalescence in oil-in-water emulsions, contributing to physical stability without the use of large quantities of synthetic polymeric thickeners.

4.3 Lipid Nanoparticle Matrix Mechanism (Drug Delivery)

Nanostructured lipid carriers (NLCs) are gaining attention as the new generation of lipid vehicles; these carriers consist of saturated lipids with small drops of liquid oil dispersed into the inner lipid matrix and are stabilized by a surfactant. NLCs incorporate both solid and liquid lipids in their cores, resulting in a more disordered lipid structure. This structural characteristic allows for higher drug loading capacity and improved drug release kinetics compared to solid lipid nanoparticles (SLNs). The ratio between solid lipid (e.g., cetyl palmitate), liquid oil (e.g., caprylic triglyceride), and surfactant (e.g., polysorbate 80) plays a critical role in determining the entrapment efficiency and stability of therapeutic agents in vivo.

5. Scientific Evidence by Area of Use

5.1 Skin Conditioning, Emolliency, and Moisturization

Cetyl palmitate's role as a skin-conditioning emollient is its best-established application, supported by decades of cosmetic ingredient safety assessments rather than randomized clinical trials per se. Moisturizers containing 2.5–2.7% cetyl palmitate were minimally irritating and produced no signs of sensitization, phototoxicity, or photo-contact allergenicity in human skin testing reviewed by the Cosmetic Ingredient Review (CIR) Expert Panel. Formulations containing cetyl palmitate at a concentration of 2.7% were minimally irritating and produced no signs of sensitization, phototoxicity, or photo contact allergenicity in studies reviewed as part of the 1982 CIR safety assessment.

Evidence strength: The emollient/skin-conditioning evidence for cetyl palmitate is based on formulation-level human patch testing and ingredient safety review, not on large randomized controlled trials specifically isolating cetyl palmitate's effect on skin hydration outcomes. As such, evidence is broadly accepted in regulatory and industry contexts but does not meet the standard of high-quality clinical trial evidence for a specific health claim.

5.2 Drug Delivery — Topical and Dermal Applications

The solid lipids most frequently used to prepare NLC include cetyl palmitate, stearic acid, glyceryl monostearate/monostearin, glyceryl behenate, and glyceryl palmitostearate. Cetyl palmitate-based NLC systems have been studied for delivery of a wide range of dermatologically relevant molecules.

A key in vitro study by Teeranachaideekul, Souto, Junyaprasert, and Müller (2007), published in European Journal of Pharmaceutics and Biopharmaceutics, examined cetyl palmitate-based NLCs for topical delivery of Coenzyme Q10 (CoQ10). In this study, NLCs composed of cetyl palmitate with various amounts of caprylic/capric triacylglycerols were prepared and CoQ10 was incorporated due to its high lipophilic character. A nanoemulsion composed solely of liquid lipid was prepared for comparison. By photon correlation spectroscopy, a mean particle size in the range of 180–240 nm with a narrow polydispersity index lower than 0.2 was obtained, and entrapment efficiency was 100% in all cases. Using static Franz diffusion cells, in vitro release studies demonstrated that Q10-loaded NLC possessed a biphasic release pattern, in comparison to Q10-loaded nanoemulsions of similar composition, which showed a nearly constant release.

CBD-loaded NLCs were prepared using cetyl palmitate as a solid lipid and stabilized with Tego® Care 450 or poloxamer 188 by high-pressure homogenization; the CBD extract was loaded at 1% w/w. Encapsulation of the CBD extract in NLCs enhanced its chemical stability after exposure to simulated sunlight (1000 kJ/m²) compared to that of the CBD extract in ethanolic solution.

Cetyl palmitate has also been used as a solid lipid component in NLC formulations for resveratrol delivery. All these nanocarriers were prepared using cetyl palmitate as a solid lipid of generally regarded as safe (GRAS) status, and isopropyl myristate as a liquid lipid, commonly used in pharmaceutical and cosmetic formulations.

Evidence strength: All topical NLC drug delivery studies involving cetyl palmitate identified in the literature are in vitro or ex vivo in nature (Franz diffusion cell assays, cell viability studies, and excised skin penetration experiments). No large-scale human clinical trials evaluating cetyl palmitate-based NLCs as delivery systems for any specific therapeutic indication have been identified in the peer-reviewed literature. The research base is preclinical and pharmaceutical-formulation focused.

5.3 Drug Delivery — Parenteral Applications

Research has examined the formulation of NLCs for the parenteral delivery of the anticancer drug all-trans retinoic acid (ATRA). The ATRA was incorporated into NLC by the de novo emulsification method. NLC was formulated using a blend of solid lipids (cetyl palmitate) and liquid lipids at a weight ratio of 1:1. ATRA-loaded NLC had an average size of less than 200 nm (141.80 to 172.95 nm) with a narrow PDI and negative zeta potential that was within an acceptable range for intravenous injection. These studies are in vitro/preclinical and do not constitute clinical evidence of efficacy.

5.4 Drug Delivery — Pulmonary Route

Novel NLC formulations were prepared via ultrasonication method, employing five solid lipids including cetyl palmitate, along with liquid lipids in 1:3 w/w ratios for pulmonary drug delivery of beclomethasone dipropionate via medical nebulizers. Again, this research is preclinical. No clinical studies involving cetyl palmitate-based pulmonary NLCs in human patients have been identified.

5.5 Potential Use in Neurological Drug Delivery

Cetyl palmitate-based NLCs were formulated to enhance the delivery of Mucuna pruriens extract, a natural source of levodopa, for Parkinson's disease therapy. Two liquid lipids, oleic acid and linoleic acid, were compared for their impact on the physicochemical properties of the NLC formulations. Both formulations demonstrated sustained release patterns in pH 7.4 media, with linoleic acid-containing NLCs showing higher cumulative drug release; drug release was lower in pH 1.2, indicating protection of the extract in acidic conditions. The results highlight the importance of lipid composition in modulating drug release and bioavailability, providing a foundation for further in vivo studies. This research is exclusively preclinical (in vitro characterization). No human data exist.

5.6 Sunscreen and Photoprotection

The choice of the ester influences both the solubility and spreadability of sunscreen agents and their ability to penetrate the skin. Like palmitic acid, cetyl palmitate absorbs infrared light from sunlight and is used as a protective ingredient in sunscreens, moisturizers, and anti-aging treatments. Cetyl palmitate's role in sunscreen formulations is primarily as a functional excipient — providing texture, stability, and potential spreading improvement — rather than as a UV-absorbing active ingredient in itself.

6. Body Systems and Health Areas of Association

6.1 Integumentary System (Skin and Hair)

In cosmetics, cetyl palmitate has an emollient function, forming a lipid film over the skin which reduces water loss from the stratum corneum. It is characterized by a dry touch and its ability to improve the texture and stability of emulsions; thanks to its emollient properties and excellent sensory profile, it can be used in different types of cosmetic formulations, from skincare to haircare.

Cetyl palmitate can be used as a surfactant in shampoos, assists in creating a creamy texture, and enhances application by helping the product spread more easily throughout the hair, thereby improving manageability and the overall feel.

In decorative and color cosmetics, in decorative cosmetics such as foundations, lipsticks, eyeliners, and concealers, it acts as a texturizing agent.

6.2 Pharmaceutical Drug Delivery — General

In specific formulations, cetyl palmitate is incorporated into wound dressings and sustained-release systems, leveraging its slow melting behavior to control drug release over time; for instance, it appears in antibiotic creams such as those containing nystatin. Its emollient characteristics, extended from cosmetic applications, support skin barrier function in these medical contexts.

Emerging research highlights cetyl palmitate's role in nanotechnology as a lipid matrix for solid lipid nanoparticles (SLNs), enabling efficient encapsulation and targeted delivery of drugs like insulin or anticancer agents.

6.3 Oncology-Adjacent (Preclinical Only)

In preclinical research, cetyl palmitate-based NLC systems have been used to encapsulate anticancer agents, including all-trans retinoic acid, with the aim of improving bioavailability and reducing systemic toxicity. The anticancer efficacy of ATRA-loaded NLC on HL-60 and HepG2 cells was studied in cell culture experiments. No clinical oncology data involving cetyl palmitate as a functional excipient exist at the time of writing.

7. Dosage Forms and Concentrations Reported in Studies

7.1 Topical and Cosmetic Concentrations

Clinical data on cetyl palmitate were limited to concentrations of 2.7% in the CIR safety assessments. The independent Cosmetic Ingredient Review panel found cetyl palmitate safe as used in cosmetics, where its usage is usually in concentrations of 2.7% or less.

7.2 NLC and SLN Formulation Concentrations (Research Settings)

NLCs composed of cetyl palmitate with various amounts of caprylic/capric triacylglycerols were prepared and Coenzyme Q10 has been incorporated in such carriers. By photon correlation spectroscopy, a mean particle size in the range of 180–240 nm with a narrow polydispersity index lower than 0.2 was obtained; the entrapment efficiency was 100% in all cases.

NLC for parenteral delivery was formulated using a blend of solid lipids (cetyl palmitate) and liquid lipids at a weight ratio of 1:1, producing particles of average size less than 200 nm (141.80 to 172.95 nm) with a narrow PDI and negative zeta potential within an acceptable range for intravenous injection.

In CBD-loaded NLC formulations prepared using cetyl palmitate as solid lipid, the CBD extract was loaded at 1% w/w. All formulations showed particle sizes between 160 and 200 nm with PDIs less than 0.10.

7.3 Pharmaceutical Excipient (Ointment and Cream Bases)

Cetyl palmitate functions as an emollient and contributes specific body and texture to the majority of cream and lotion products; it functions as a base for ointments, cerates, and emulsions. Specific mass-fraction concentrations used as a stiffening agent or ointment base excipient are not consistently reported across studies; formulation-level concentration data are product-specific and governed by pharmacopeial monograph guidance.

8. Safety Considerations

8.1 Regulatory Safety Conclusions

The CIR Expert Panel evaluated the scientific data and concluded that ethylhexyl palmitate, cetyl palmitate, and isopropyl palmitate were safe as cosmetic ingredients. In 2001, the CIR Expert Panel reaffirmed that cetyl palmitate (along with ethylhexyl palmitate and isopropyl palmitate) is safe for use in cosmetics, based on data showing no acute toxicity, mutagenicity, or carcinogenicity.

Cetyl palmitate has a generally regarded as safe (GRAS) status as a solid lipid used in nanoparticle formulations.

8.2 Acute and Subchronic Toxicity Data

The acute oral LD₅₀ is estimated from studies with rats to be greater than 14.4 g/kg for cetyl palmitate. In oral toxicity studies with rats, doses of 5.00, 7.12, 10.14, and 14.43 g of cetyl palmitate per kg were administered as a 50% slurry in corn oil to 10 rats at each dosage; diarrhea in one rat at each level was observed three hours following administration, with no mortality reported. Acute studies with rabbits showed no evidence of dermal toxicity. Rabbit skin tests with the palmitates showed that they are nonirritating and nonsensitizing. Draize rabbit eye irritation tests on the palmitates produced either no or only very slight ocular irritation.

8.3 Human Skin Irritation and Sensitization

Moisturizers containing 2.5–2.7% cetyl palmitate were minimally irritating and produced no signs of sensitization, phototoxicity, or photo-contact allergenicity. Formulations containing cetyl palmitate at a concentration of 2.7% were minimally irritating and produced no signs of sensitization, phototoxicity, or photo contact allergenicity.

In vitro cell viability studies revealed that most cell lines can tolerate up to 1 mg/mL of lipid doses of drug-free NLCs.

8.4 In Vitro Cellular Tolerability (NLC Formulations)

In vitro cell viability studies revealed that most cell lines can tolerate up to 1 mg/mL of lipid doses of drug-free NLCs. Many studies provided evidence for adequate cellular tolerability for positively charged lipid-based nanocarriers. These findings inform the use of cetyl palmitate as a matrix lipid in nanoparticle systems, though in vitro tolerability does not substitute for in vivo clinical safety evaluation.

8.5 Pharmacopeial Compliance and Regulatory Status

Cetyl palmitate must comply with compendial standards such as those set by the European Pharmacopoeia (Ph.Eur.) and the United States Pharmacopeia (USP). Ensuring compliance with these standards is essential for its use in pharmaceutical applications. Manufacturers must obtain necessary certifications and approvals, including those related to ISO 17034 and ISO/IEC 17025, to ensure the quality and safety of the product.

8.6 Known Limitations and Gaps in Safety Data

The Expert Panel noted that clinical data on cetyl palmitate were limited to concentrations of 2.7%. The absence of formal clinical trials at higher concentrations means the safety profile at concentrations above those typical in cosmetic products (where it is used at or below 2.7%) has not been formally characterized in human subjects. As a pharmaceutical excipient in NLC/SLN systems, cetyl palmitate's long-term systemic safety following repeated parenteral administration is not established in humans. All available pharmacokinetic and tolerability data for cetyl palmitate-based nanoparticle systems come from preclinical in vitro experiments.

8.7 Ecological Considerations

Cetyl palmitate is a product of natural and biodegradable origin. Plant-derived grades represent a sustainable alternative to the historically used marine-mammal-derived spermaceti, and RSPO-certified palm-based production has become a standard for responsibly sourced commercial grades.

References

Health Conditions

Health conditions that Cetyl palmitate may help support.

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Body Systems

Body systems that Cetyl palmitate may help support.

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Cetyl palmitate | Caring Sunshine