Study of Croscarmellose Sodium: Granular vs Fibrous and Cotton Linter vs Wood Pulp

Croscarmellose sodium (CCS) is one of the most widely used super disintegrants in tablets and capsules because it can rapidly attract and absorb water. CCS is produced by reacting cellulose with sodium monochloroacetic acid to form sodium carboxymethyl cellulose and then cross-linking the polymer. Cross‑linking creates an insoluble but highly hydrophilic network; when water enters this network, the polymer swells many times its original volume and the mechanical stresses break the tablet apart. Manufacturers offer CCS in various physical forms (granular vs fibrous) and from different cellulose sources (cotton linters vs wood pulp). This report compares these variants and evaluates their effect on immediate‑release (IR) performance and disintegration.

How Croscarmellose Sodium Works

• Hydrophilic, cross‑linked polymer – CCS’s backbone is sodium carboxymethyl cellulose; cross‑linking between chains reduces solubility but leaves numerous hydrophilic carboxylate groups. In a dry tablet the polymer is a porous network of fibres and capillaries. When water contacts the tablet, it wicks into these fibres; hydrogen bonds between water molecules and cellulose hydroxyl groups (OH groups) create rapid water uptake. The hydrophilic network swells dramatically, generating mechanical stresses that crack the tablet.

• Wicking & swelling – A comparative study of four disintegrants reported that highly swelling materials like sodium starch glycolate (SSG) and CCS show the largest water uptake, while capillary‑driven materials like microcrystalline cellulose (MCC) absorb much less water. In neutral pH (6.8), the water‑uptake rate of CCS was ~0.55 g/s; this decreased to 0.26 g/s at acidic pH (1.0). The order of swelling ability and water sorption was SSG > CCS > crospovidone > MCC

• Use levels – Market analyses show that adding 0.5–5 % CCS can reduce tablet disintegration time from minutes to < 30 seconds in many IR formulations. Because CCS swells at low loadings, typical use levels are 1–4 %. Exceeding ~5 % often does not further reduce disintegration but can weaken tablets.

Granular vs Fibrous CCS

Physical and processing differences

Fibrous grade: Most commercial CCS (e.g., Ac‑Di‑Sol, VIVASOL, Primellose) is described as a white, fibrous, free‑flowing powder. The fibrous structure comes from the native cellulose fibres that are only partly broken down during carboxymethylation and cross‑linking. Product literature emphasises that these long fibres form a network of micro‑capillaries. For example, cotton fibres have a fine primary wall containing continuous capillaries; these capillaries pull liquids into the fibre and contribute to cotton’s wickability. When this fibre network is cross‑linked to form CCS, water can rapidly permeate along fibres and swell them, leading to fast disintegration.

Granular grade: Some suppliers offer CCS in granular form. However, compressing fibres into granules can reduce exposed capillary channels; thus a slightly higher concentration may be needed to achieve the same disintegration efficiency.

Impact on disintegration

Evidence comparing granular to fibrous CCS is mostly from manufacturer data and empirical formulation experience; peer‑reviewed comparisons are scarce. Some important considerations:

1. Wicking efficiency – The fibrous network of CCS provides excellent water wicking. Pehel Specialities, which produces Dis‑In‑Cel from cotton linters, reports that long fibres “ensure superior wicking and rapid tablet disintegration” and that the product is effective at low concentrations (1–2 %. Granular material may decrease the number of open capillaries per particle, requiring slightly higher levels to achieve similar wicking and achieving lower wicking.

2. Compression and hardness – Because CCS is loosely bonded, tablets containing large amounts of fibrous CCS can be weak. Granular CCS particles pack better and may increase tablet hardness at equivalent concentrations. However, if granulated too strongly, the wicking action may be partially compromised.

Verdict: fibrous vs granular

• Speed of disintegration: Fibrous CCS typically delivers slightly faster disintegration at lower concentrations because its uncompressed fibres provide more capillaries for water uptake. Granular CCS may require higher levels to compensate for reduced wicking.

• Best practice: For immediate‑release tablets requiring rapid break‑up, formulators often use fibrous CCS or a granular grade that retains fibre-like structure.

Cotton‑Linter vs Wood‑Pulp CCS

Feedstock characteristics

CCS can be synthesized from two main sources of cellulose: cotton linters (short fibres recovered from cottonseed) and refined wood pulp. The cellulose chain length and crystalline structure differ significantly between cotton and wood.

• Cotton fibres – Cotton cellulose has a high degree of polymerization (9 000–15 000 anhydroglucose units) and high crystallinity (~73 %). Mature fibres contain six structural layers, including a primary wall made of fine fibrils and capillaries that contribute to exceptional wickability. In the cotton‑linter grades of CCS (e.g., Ac‑Di‑Sol SD‑711, VIVASOL, Dis‑In‑Cel CL), these long fibres remain largely intact; the resulting CCS particles are fibrous with long, open networks that wick water quickly. Because cotton fibres are relatively pure cellulose, little hemicellulose or lignin remains after processing.

• Wood pulp – Wood cellulose has shorter polymer chains (600–1 500 units) and lower crystallinity (~35 %). Wood fibres are shorter and contain more hemicellulose and lignin, requiring extensive purification to reach pharmaceutical quality.

Performance comparison

1. Wicking and water uptake – Cotton‑based CCS tends to have longer fibres and a more open network, which enhances capillary action. A fibrous cotton structure may also provide more surface area and pores for water to enter.

2. Particle size distribution – Cotton‑linter CCS products often have slightly larger median particle sizes due to the longer fibres (D50 ~40–50 µm). Wood‑pulp CCS tend to have smaller particles.

3. Swelling capacity –The water‑uptake rate and swelling ability of CCS significantly differ between cotton and wood‑derived grades when particle size and cross‑linking density are controlled. Formulators observe faster swelling for cotton‑derived CCS at the same concentration due to its longer fibres and higher crystallinity.

4. Regulatory and sustainability considerations – Cotton linters are non‑GMO by default but have limited supply and variable cost. Wood pulp is abundant and consistent, but some formulations require GMO‑free or allergen‑free raw materials. Pehel’s Dis‑In‑Cel WP emphasises non‑GMO wood pulp and full traceability. Sustainability is increasingly important; wood pulp originates from renewable forestry, while cotton may involve higher pesticide use.

5. Cost and availability – Wood‑pulp CCS is generally less expensive and more widely available. The global production of wood pulp exceeds 190 million metric tons per year, ensuring a reliable feedstock. Cotton‑linter CCS is manufactured by fewer suppliers and may carry a price premium.

Which is better?

• Performance – Cotton‑linter CCS often offers a faster disintegration because of its longer fibres and higher crystallinity.

• Consistency and cost – Refined wood‑pulp grades dominate the market because they provide lower cost.

• Regulatory or branding requirements – Some nutraceutical or “natural” products may specify wood‑based ingredients to avoid GMO concerns..

Impact on Immediate‑Release Formulations

The choice of CCS form and source influences IR formulations in several ways:

• Disintegration efficiency – CCS accelerates disintegration primarily via wicking and swelling. Formulations using fibrous CCS generally disintegrate faster than those with solely granular CCS. Cotton‑linter grades often show slightly faster disintegration at low use levels due to longer fibres, but properly engineered wood‑pulp grades can perform similarly.

• Combination with other disintegrants – Studies show that crospovidone and sodium starch glycolate can outperform CCS in some IR formulations. For example, a twin‑screw melt‑granulation study found that crospovidone added extragranularly produced the shortest disintegration time (78 s), while intragranular CCS alone was less effective. Many formulators therefore use CCS in combination with crospovidone or SSG to balance swelling, wicking and tablet strength.

• Intra‑ vs extragranular addition – To maintain CCS’s fibrous structure and wicking ability, at least part of the disintegrant should be added extragranularly. Intragranular CCS may become embedded within granules and lose contact with water; extragranular CCS rapidly creates channels for water penetration, leading to efficient break‑up.

• Use levels and mechanical properties – Increasing CCS concentration decreases disintegration time but reduces tablet hardness and increases friability. The optimum range is typically 1–4 % of tablet weight; exceeding 5 % seldom benefits IR release and can compromise mechanical strength. Combining CCS with other excipients (e.g., microcrystalline cellulose) can enhance hardness while maintaining quick disintegration.

Conclusions and Recommendations

1. Granular vs fibrous – Fibrous CCS provides superior wicking and faster disintegration at lower concentrations; granular CCS offers improved flow and compressibility at the expense of slightly slower disintegration. For immediate‑release tablets targeting very rapid break‑up, a fibrous grade is recommended.

2. Cotton‑linter vs wood‑pulp – Cotton‑linter CCS has longer fibres and higher crystallinity, giving better wicking.  Since refined wood pulp is widely available and cost‑effective, it dominates the CCS market. Choice should therefore be guided by supply, cost, and regulatory requirements rather than an assumption that cotton is always superior.

3. Formulation strategies for IR tablets – Use CCS at 1–4 % weight, preferably with a portion extragranular. For extremely fast disintegration, combine CCS with crospovidone or SSG. Choose fibrous or cotton‑derived grades when rapid wicking is critical; choose granular or wood‑pulp grades when flowability, cost or sustainability are priorities.

4. Critical perspective – Manufacturer claims often imply that cotton‑based or fibrous CCS dramatically outperforms wood‑pulp or granular grades. Cotton’s higher degree of polymerization and capillary network do confer advantages. Formulators should evaluate CCS grades based on objective performance data rather than marketing narratives.

   
   

By understanding how physical form, raw‑material source, and formulation strategy influence CCS performance, formulators can choose the most suitable grade for immediate‑release products, balance cost and performance, and avoid the pitfalls of relying solely on anecdotal claims.