Croscarmellose (Carboxymethylcellulose, E466, CMC), is a chemically modified derivative of cellulose. It is widely used as a thickener, stabilizer, emulsifier, and gelling agent in the food, pharmaceutical, and cosmetic industries. CMC is valued for its ability to increase viscosity and stabilize formulations, making it a versatile ingredient. Croscarmellose is a cross-linked form of CMC, primarily used in pharmaceutical products as a disintegrant in tablets and capsules.

Chemical Composition and Structure

Croscarmellose is produced by replacing the hydroxyl groups in natural cellulose with carboxymethyl groups (-CH₂COOH), which enhance its water solubility and gel-forming capabilities. Croscarmellose, a cross-linked form of CMC, has a similar structure but its chemical modification allows it to act primarily as a disintegrant in pharmaceutical tablets.

Physical Properties

It appears as a white or cream-colored powder, odorless and tasteless. It is highly soluble in water, where it forms viscous solutions or gels, making it useful as a thickener and stabilizer. Croscarmellose, on the other hand, is water-insoluble but swells rapidly in the presence of liquids, aiding in the disintegration of tablets.

Production Process

• Extraction of Cellulose: Cellulose is extracted from plant sources such as wood or cotton. This extraction process may include maceration and chemical treatment with alkaline solutions to remove lignin and hemicellulose.

• Chemical Modification: The extracted cellulose is then subjected to a carboxymethylation process, where carboxymethyl groups (-CH₂COOH) are added to the cellulose. This is achieved by treating cellulose with chloroacetic acid in the presence of a base, such as sodium hydroxide. This process transforms cellulose into Croscarmellose.

• Purification: The produced Croscarmellose is purified to remove any impurities and chemical residues. This may involve washing and filtration to ensure a high-quality product.

• Drying and Milling: Once purified, Croscarmellose is dried and milled into a fine powder to facilitate its use in formulations.

• Quality Control and Packaging: Finally, Croscarmellose undergoes quality control checks to verify its purity and functional properties. After analysis, it is packaged for distribution and use.

Applications

• Food Industry: Croscarmellose (E466) is widely used as a thickener and stabilizer in a variety of food products, including sauces, beverages, ice creams, and baked goods. It helps improve texture and stabilizes emulsions and suspensions.

In the food industry (1), it is a thickening and stabilising agent, and since the 1980s it has entered the oenological field (2).

Excessive intake of celluloses such as E465 may be associated with high risks of cardiovascular diseases (CVD).(3)

• Pharmaceuticals: Croscarmellose is used as a disintegrant in tablets and capsules, helping them dissolve quickly in the body. CMC is also used in pharmaceuticals to improve viscosity and stabilize suspensions and solutions.

• Cosmetics: In cosmetics, CMC is used as a thickening and stabilizing agent in creams, lotions, gels, and hair care products, improving texture and consistency in formulations.

INCI Functions:

Binder agent. Ingredient that is used in cosmetic, food and pharmaceutical products as an anti-caking agent with the function of making the product in which it is incorporated silky, compact and homogenous. The binder, either natural such as mucilage, gums and starches or chemical, may be in the form of a powder or liquid.

Emulsion stabilizer. Emulsions are thermodynamically unstable. Emulsion stabilisers improve the formation and stability of single and double emulsions. It should be noted that in the structure-function relationship, molar mass plays an important role.

Film-forming agent. It produces a continuous ultra-thin film with an optimal balance of cohesion, adhesion and stickiness on the skin or hair to counteract or limit damage from external phenomena such as chemicals, UV rays and pollution.

Fragrance. It plays a decisive and important role in the formulation of cosmetic products as it provides the possibility of enhancing, masking or adding fragrance to the final product, increasing its marketability.  The consumer always expects to find a pleasant or distinctive scent in a cosmetic product.

Viscosity control agent. It controls and adapts viscosity to the required level for optimal chemical and physical stability of the product and dosage in gels, suspensions, emulsions, solutions. 

Other uses

In the mining sector it is used as an additive for drilling muds and is widely used in the production of paper, textiles, paints and more.

Cellulose gum studies

• Molecular Formula : C₈H₁₆O₈
• Molecular Weight: 240.208 g/mol
• CAS: 9000-11-7
• EC Number:618-326-2
• FEMA Number: 2239

Synonyms: 

• Carboxymethyl Cellulose
• Cellulose, Carboxymethyl
• Carboxymethylcellulose
• carmellose sodium
• Carboxymethylcellulose Sodium
• Cellolax
• Carboxymethylcellulose, Sodium

References________________________________________________________________________

(1) Regolamento (CE) N° 1333/2008 del 16 dicembre 2008 sugli additivi alimentari.

Determination of carboxyméthycellulose in food products - H.D Graham, Journal of food science 1971, p 1052-1055.

(2) Stabilisation tartrique des vins par la carboxyméthylcellulose - Bulletin de l’OIV 2001, vol 74, n°841-842, p151-159.

(3) Sellem L, Srour B, Javaux G, Chazelas E, Chassaing B, Viennois E, Debras C, Salamé C, Druesne-Pecollo N, Esseddik Y, de Edelenyi FS, Agaësse C, De Sa A, Lutchia R, Louveau E, Huybrechts I, Pierre F, Coumoul X, Fezeu LK, Julia C, Kesse-Guyot E, Allès B, Galan P, Hercberg S, Deschasaux-Tanguy M, Touvier M. Food additive emulsifiers and risk of cardiovascular disease in the NutriNet-Santé cohort: prospective cohort study. BMJ. 2023 Sep 6;382:e076058. doi: 10.1136/bmj-2023-076058. PMID: 37673430; PMCID: PMC10480690.

Arca HC, Mosquera-Giraldo LI, Bi V, Xu D, Taylor LS, Edgar KJ. Pharmaceutical Applications of Cellulose Ethers and Cellulose Ether Esters. Biomacromolecules. 2018 Jul 9;19(7):2351-2376. doi: 10.1021/acs.biomac.8b00517. 

Abstract. Cellulose ethers have proven to be highly useful natural-based polymers, finding application in areas including food, personal care products, oil field chemicals, construction, paper, adhesives, and textiles. They have particular value in pharmaceutical applications due to characteristics including high glass transition temperatures, high chemical and photochemical stability, solubility, limited crystallinity, hydrogen bonding capability, and low toxicity. With regard to toxicity, cellulose ethers have essentially no ability to permeate through gastrointestinal enterocytes and many are already in formulations approved by the U.S. Food and Drug Administration. We review pharmaceutical applications of these valuable polymers from a structure-property-function perspective, discussing each important commercial cellulose ether class; carboxymethyl cellulose, methyl cellulose, hydroxypropylcellulose, hydroxypropyl methyl cellulose, and ethyl cellulose, and cellulose ether esters including hydroxypropyl methyl cellulose acetate succinate and carboxymethyl cellulose acetate butyrate. We also summarize their syntheses, basic material properties, and key pharmaceutical applications.