Sodium stearyl fumarate
[CAS# 4070-80-8]

Identification

• Classification: Food additive >> Flour treatment agent
• Name: Sodium stearyl fumarate
• Synonyms: Sodium octadecyl fumarate
• Molecular Formula: C₂₂H₃₉NaO₄
• Molecular Weight: 390.53
• CAS Registry Number: 4070-80-8
• EC Number: 223-781-1
• SMILES: CCCCCCCCCCCCCCCCCCOC(=O)/C=C/C(=O)[O-].[Na+]

Safety Data

• Hazard Symbols: GHS07 Warning
• Hazard Statements: H315-H319
• Precautionary Statements: P264-P264+P265-P280-P302+P352-P305+P351+P338-P321-P332+P317-P337+P317-P362+P364

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Eye irritation	Eye Irrit.	2	H319
Skin irritation	Skin Irrit.	2	H315
Specific target organ toxicity - single exposure	STOT SE	3	H335
Flammable solids	Flam. Sol.	2	H228

Discovory and Applicatios

Sodium stearyl fumarate is a salt formed from stearyl fumaric acid and sodium. It is an excipient commonly used in pharmaceutical formulations, primarily as a lubricant and glidant in tablet manufacturing. Chemically, sodium stearyl fumarate consists of a fumaric acid backbone, which is a dicarboxylic acid with a trans double bond, esterified with stearyl alcohol, a long-chain fatty alcohol, and neutralized to the sodium salt form. This combination imparts both hydrophobic and ionic properties to the molecule.

The discovery of fumaric acid and its derivatives dates back to the 19th century when fumaric acid was first isolated from natural sources such as Fumaria officinalis and various plants. The modification of fumaric acid to produce esters like stearyl fumarate and their salts arose from the need for effective lubricants and functional excipients in solid dosage forms. Sodium stearyl fumarate was developed as an alternative to traditional lubricants such as magnesium stearate, offering improved flow properties and reduced interference with tablet disintegration and dissolution.

In pharmaceutical manufacturing, sodium stearyl fumarate serves as an effective lubricant that reduces friction between the tablet formulation and the machinery during compression and ejection. Unlike some lubricants, sodium stearyl fumarate tends to have minimal impact on the bioavailability of the active pharmaceutical ingredient, making it suitable for formulations where rapid dissolution is important. It also functions as a glidant, enhancing powder flowability, which improves the uniformity and consistency of tablet weight and content.

Sodium stearyl fumarate is favored in formulations that require rapid or immediate release of the active ingredient because it does not significantly hinder water penetration or tablet disintegration. It is also compatible with a wide range of active substances and other excipients, including binders and fillers. Its stability under typical manufacturing and storage conditions contributes to its widespread use.

Beyond pharmaceutical applications, sodium stearyl fumarate finds limited use in other industries. It may be utilized in some cosmetic formulations as an emulsifier or stabilizer, although this is less common compared to its role in solid oral dosage forms.

From a chemical perspective, sodium stearyl fumarate is stable and non-reactive under normal conditions. The fumarate moiety is resistant to hydrolysis in the dry state, and the stearyl chain provides hydrophobicity that enhances its lubricant function. The presence of the sodium ion improves solubility in water compared to non-salt forms, although the compound remains primarily hydrophobic overall.

Toxicological evaluations indicate that sodium stearyl fumarate is safe for use as an excipient at typical concentrations. It exhibits low acute toxicity and does not cause significant irritation or sensitization. Regulatory agencies have approved its use in pharmaceutical products based on safety data and its long history of use.

Manufacturers prefer sodium stearyl fumarate in certain formulations due to its balance of lubricating efficiency and minimal negative effect on tablet dissolution profiles. It is often used at concentrations between 0.5% and 2% by weight in tablet formulations, depending on the specific manufacturing requirements and desired tablet characteristics.

In summary, sodium stearyl fumarate is a valuable pharmaceutical excipient developed to improve the manufacturing and performance of solid dosage forms. Its chemical structure combines hydrophobic stearyl chains with the ionic fumarate salt, giving it properties that facilitate powder flow and reduce friction during tablet compression without adversely affecting drug release. These features ensure its continued use and importance in modern pharmaceutical technology.

References

2006. Packed column supercritical fluid chromatography of sodium stearyl fumarate aqueous suspension. Journal of Pharmaceutical and Biomedical Analysis, 40(4).
DOI: 10.1016/j.jpba.2005.07.049

2024. A Rapid 3-Day Excipient Screening Methodology and its Application in Identifying Chemical Stabilizers for Solid Formulations with Mixed Mechanisms of Degradation. AAPS PharmSciTech, 25(1).
DOI: 10.1208/s12249-023-02730-5

2024. Effect of lubricants type and particle size on the rheological properties and aerosolization behavior of dry powder inhalers. International Journal of Pharmaceutics, 666.
DOI: 10.1016/j.ijpharm.2024.124911