Croscarmellose Sodium (CAS#9000-11-7) – Superdisintegrant for Tablets

1. Properties:

• Appearance and Physical Form: Croscarmellose sodium is a white to off‑white, fibrous, free‑flowing powder, odorless, with a characteristic slightly fibrous feel. The product is free from visible foreign particles and exhibits good compressibility. Its density is approximately 0.48 g/cm³, and its bulk density ranges from 0.45 to 0.65 g/mL (loose) and 0.70 to 0.90 g/mL (tapped).
• Solubility: Croscarmellose sodium is practically insoluble in water, acetone, ethanol, and toluene. However, it has a remarkable ability to rapidly absorb many times its own weight of water, swelling to approximately 20–30 times its original volume due to its cross‑linked polymer network. It also swells in 1 M sodium hydroxide solution to form a viscous suspension. The product is highly hygroscopic.
• Chemical Properties: Croscarmellose sodium is the sodium salt of a cross‑linked, partly O‑(carboxymethylated) cellulose. Its degree of substitution (DS) typically ranges from 0.60 to 0.85, indicating that 60–85% of the hydroxyl groups in the cellulose backbone are substituted with carboxymethyl (–CH₂–COONa) groups. A small proportion (typically 1–6%) of these carboxymethyl groups participate in inter‑ and intra‑molecular cross‑links, forming a stable three‑dimensional polymer network. The material does not dissolve in water because its cross‑links prevent complete hydration; instead, it swells by capillary action. The aqueous dispersion of croscarmellose sodium has a pH between 5.0 and 7.0. The product is thermally stable and does not melt on heating; exposure to high temperatures causes charring prior to melting. It is chemically inert toward most active pharmaceutical ingredients and shows no evidence of hydrogen bonding with APIs in solid dosage forms.

2. Applications:

Pharmaceutical Industry (Primary):

• Superdisintegrant for Tablets and Capsules: Croscarmellose sodium is one of the most efficient superdisintegrants in pharmaceutical technology. When solid dosage forms come into contact with water or gastrointestinal fluids, croscarmellose sodium rapidly absorbs water by capillary action, causing the cross‑linked polymer matrix to swell immediately. The rapid swelling generates a pressure that ruptures the tablet matrix, leading to fast disintegration. This mechanism relies on a combination of swelling, wicking, and deformation recovery effects.
• Direct Compression and Wet Granulation: Croscarmellose sodium can be used in both direct compression and wet granulation processes. In direct compression, it is used at a level of 1–2% of total tablet weight; in wet granulation, levels up to 5% are employed to ensure good tablet disintegration. It can also be used in both the intragranular and extragranular phases of granulation processes to maximise performance.
• Fast‑Disintegrating and Orally Dispersible Tablets (ODT): Due to its exceptional swelling properties, croscarmellose sodium is the excipient of choice for fast‑disintegrating and orally dispersible tablets. It shortens tablet disintegration time, thereby increasing disintegration efficiency and improving drug dissolution. The product does not contain peroxides, which ensures better active pharmaceutical ingredient (API) stability in sensitive formulations.
• Capsules and Granules: Croscarmellose sodium is used as a disintegrant in hard capsules, soft granules, and pellets, ensuring rapid breakup and uniform drug release.
• Bioavailability Enhancement: By promoting rapid and complete tablet disintegration, croscarmellose sodium helps the active pharmaceutical ingredient to be released faster, thereby enhancing drug dissolution, absorption, and overall bioavailability.

Food Industry:

• Emulsifier and Stabilizer (E468): Croscarmellose sodium is approved as a food additive with the E‑number E468 and functions as an emulsifier and stabilizer in various food products. It helps maintain product consistency, prevents clumping in powdered formulations, and provides water‑retaining properties in processed foods. Typical applications include powdered drinks, baked goods, puffed foods, biscuits, and dietary supplements.
• Suspension Stabilizer: Used to stabilise emulsions and suspensions in liquid and semi‑solid food products, improving texture and shelf‑life stability.

Cosmetics and Personal Care:

• Thickener and Stabilizer: In cosmetic formulations, croscarmellose sodium serves as an effective thickener and stabilizer for lotions, creams, powders, and other personal care products. It improves texture, provides a smooth and pleasant feel, and prevents phase separation.
• Facial Masks and Cleansers: Used in powder‑based facial masks, exfoliating cleansers, and dry shampoo formulations to impart consistency, improve spreadability, and enhance water absorption upon application.
• Hygiene Products: Incorporated into intimate hygiene powders, baby powders, and body powders for its absorbency, anti‑clumping, and skin‑feel properties.

Industrial Applications:

• Textile Processing: Croscarmellose sodium is used as a sizing agent, water‑retaining agent, and thickener in textile printing and finishing. It improves fabric hand feel, enhances dye uptake uniformity, and reduces water loss during processing. It also functions as a chelating agent and flocculating agent in textile wastewater treatment.
• Paper Manufacturing: Serves as a surface‑sizing agent, coating binder, and water‑retention aid in paper production. It improves paper strength, smoothness, printability, and barrier properties.
• Electronics: Used as a binder and thickening agent in lithium‑ion battery electrode slurries and conductive pastes, improving electrode stability and coating uniformity.
• Paints and Coatings: Acts as a thickening agent and rheology modifier in water‑based paints, adhesives, and industrial coatings, preventing sagging and improving application properties.
• Ceramics and Construction: Used as a binder and plasticiser in ceramic glazes, dry mortar formulations, and wall putties, providing improved workability, water retention, and adhesion.
• Pesticides and Agrochemicals: Functions as a suspending agent, emulsifier, and thickener in pesticide suspensions and wettable powders, improving dispersion stability and field application efficiency.
• Leather Processing: Used as a finishing aid and binder in leather coating formulations, enhancing surface smoothness, flexibility, and water resistance.
• Explosives and Fire Starters: Croscarmellose sodium is used as a thickening or gelling agent in chafing fuel (gel alcohol fuel) used for outdoor cooking, camping, and emergency heating. It is also employed as a binding agent in coal briquettes and charcoal briquettes for barbecue and industrial fuel applications.
• Oil and Gas Drilling Fluids: Applied as a viscosity modifier and fluid loss control additive in water‑based drilling fluids for oil and gas exploration, improving hole cleaning, cutting transport, and borehole stability.
• Pharmaceutical Coatings (Anti‑Adhesion): In combination with chitosan and hyaluronic acid, croscarmellose sodium is used in anti‑adhesion gels and barrier formulations to prevent tissue and organ adhesion after surgical operations or injuries. The product is biocompatible and exhibits very high bioavailability.

3. Preparation Method:

• Laboratory Method: Croscarmellose sodium is typically prepared by a two‑step process: (1) Sodium carboxymethylcellulose (CMC) is first prepared by reacting alkali‑treated cellulose (alkali cellulose) with sodium chloroacetate under controlled conditions, yielding CMC with a degree of substitution (DS) of 0.60–0.85. (2) The resulting CMC is then subjected to controlled cross‑linking using a bifunctional cross‑linking agent such as epichlorohydrin, sodium trimetaphosphate, or a citric acid derivative in an aprotic solvent medium under mild heating and stirring. The cross‑linking reaction creates a three‑dimensional network that renders the final product water‑insoluble but highly swellable.
• Industrial Process: Industrial production of high‑quality croscarmellose sodium for pharmaceutical, food, and cosmetic applications follows a similar two‑step route: (1) Alkalization: Refined cellulose derived from wood pulp or cotton linters is steeped in sodium hydroxide (NaOH) solution to produce alkali cellulose. (2) Etherification: The alkali cellulose is reacted with sodium chloroacetate (monochloroacetic acid, sodium salt) to form sodium carboxymethylcellulose (CMC) with a DS of approximately 0.70–0.85. (3) Cross‑linking: The CMC is cross‑linked using a heat‑induced esterification process (e.g., with citric acid) or chemical cross‑linking agents (e.g., epichlorohydrin) under controlled temperature and agitation to create an internally cross‑linked polymer network. (4) Purification and Drying: The cross‑linked product is washed with aqueous alcohol solutions to remove by‑products (sodium chloride and sodium glycolate), followed by drying, milling, and sieving to meet pharmacopoeial particle size specifications (e.g., 90–100% passing through #200 mesh). The final product is a white to off‑white, fibrous, free‑flowing powder meeting USP/NF, Ph. Eur., and BP monograph requirements.

4. Safety Information:

• Hazard Classification: According to CLP Regulation (EC) No 1272/2008 and GHS, croscarmellose sodium is generally classified as non‑hazardous or of very low hazard, with most commercial grades carrying hazard statement H412 (Harmful to aquatic life with long‑lasting effects). The product is not classified as hazardous for supply/use, and no hazard label is required for most grades, though some manufacturers may include hazard statements as a precaution. The product is non‑flammable, stable, and does not present significant reactivity hazards under normal handling conditions.
• Health Hazards:
  • Eye Contact: May cause slight mechanical irritation due to dust particles; not classified as corrosive or severely irritating.
  • Skin Contact: Generally non‑irritating to skin; may cause mild irritation in sensitive individuals.
  • Inhalation: Inhalation of airborne dust may cause mild respiratory tract irritation, coughing, or sneezing in sensitive persons. Prolonged or repeated inhalation of high dust concentrations may cause respiratory discomfort.
  • Ingestion: Low oral toxicity (LD50 > 10,000 mg/kg in rats). Ingestion of large amounts may cause mild gastrointestinal discomfort due to bulking effects. Do not induce vomiting unless directed by medical personnel.
• Personal Protection:
  • Respiratory protection: Use a dust mask (N95 or P2 respirator) if airborne dust concentrations exceed occupational exposure limits or in poorly ventilated areas.
  • Eye protection: Safety goggles or dust‑resistant safety glasses to prevent mechanical eye irritation.
  • Skin protection: Protective gloves and laboratory coat are recommended to minimise skin contact and dust exposure.
  • General hygiene: Wash hands thoroughly after handling. Do not eat, drink, or smoke in work areas. Minimise dust generation and avoid breathing dust.
• First Aid Measures:
  • Eye Contact: Flush eyes gently with plenty of water for at least 15 minutes, occasionally lifting the upper and lower eyelids. Remove contact lenses if present and easy to do. Seek medical attention if irritation persists.
  • Skin Contact: Wash affected area with plenty of soap and water. Remove contaminated clothing. Seek medical advice if irritation develops.
  • Inhalation: Move person to fresh air. Keep at rest in a position comfortable for breathing. If symptoms (coughing, throat irritation) persist, seek medical advice.
  • Ingestion: Rinse mouth immediately. Do NOT induce vomiting. Seek immediate medical attention if large amount is ingested.
• Fire & Explosion Hazards: Croscarmellose sodium is not combustible but may burn if involved in a fire. Accumulation of settled dust may form explosive concentrations in air when disturbed and dispersed, as with any organic dust. In case of fire, use water spray, foam, dry powder, or CO₂ as extinguishing media. Thermal decomposition may produce carbon monoxide, carbon dioxide, and sodium oxides. Prevent dust deposition; use spark‑proof equipment and maintain good housekeeping.
• Environmental Precautions: Croscarmellose sodium is harmful to aquatic life with long‑lasting effects (H412). Avoid direct release into natural water bodies, drains, or the environment. Large spills should be contained and prevented from entering waterways. The product is generally considered to be biodegradable (cellulose‑derived polymer). Comply with local environmental regulations for disposal.
• Storage & Stability: Store in tight, well‑closed containers in a cool, dry, well‑ventilated area away from direct sunlight, heat sources, strong oxidising agents, and moisture. The product is hygroscopic; protect from atmospheric moisture to prevent caking and lump formation. Under recommended storage conditions (below 30°C, low humidity), croscarmellose sodium has a shelf life of 36 months (3 years) from the date of manufacture when stored in tightly closed original containers. The product is stable and does not decompose under normal storage conditions.
• Regulatory Compliance: Croscarmellose sodium (CAS#9000-11-7) is listed on EINECS, TSCA, DSL, AICS, NZIoC, ENCS, KECI, PICCS, and other regional chemical inventories. It is approved as a pharmaceutical excipient conforming to USP/NF, Ph. Eur. (monograph 0985), BP, and JP standards. As a food additive E468, it is approved for use as an emulsifier and stabiliser in many jurisdictions. The product is widely used in over‑the‑counter (OTC) and prescription pharmaceuticals, dietary supplements, food products, cosmetics, and industrial applications. Always consult the Safety Data Sheet (SDS) and local regulations for complete safety, environmental, and regulatory information specific to each product grade and application jurisdiction.