Cellulose as excipient

What is Cellulose?

Cellulose was discovered by the French chemist Anselme Payen in 1838; he discovered that cell walls in plants and trees are made of lignin and cellulose. Payen isolated Cellulose from wood, characterized it and determined its chemical formula. As the most abundant polymer in the world being reproduced constantly by trees, plants, fungus and bacteria, the potential of cellulose was recognized and since then a great deal of work has been done to find applications  and to improve extraction and separation procedures.

Today wood is the most common source of cellulose used in the industry. Although cotton can be used to obtain high grades of cellulose, cotton is avoided by the food and pharmaceutical industry to exclude statements about the possible use of cellulose that originates from genetically modified plants. Non-genetically modified cotton is available but it is costly to prove that it does not contain modified material.

Read more below about the cellulose composition and purity,  cellulose properties and cellulose characterization.

Look here for information about microcrystalline cellulose and hypromellose.

Cellulose Characterization Services

Be in control of your product!

offers fast and flexible hands-on cellulose characterization services to reveal and compare hidden cellulose properties like :

the presence of potential reactive impurities or functional groups, degradation products and related substances, just like molecular weight distributions, reducing power and many other featured characteristics.

In addition, we can help users of excipients to pick the most appropriate cellulose manufacturer, select the most suitable cellulose grade for their finished dosage form, or define customized cellulose specifications to control product performance, quality and safety.
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Cellulose monomers and cellulose structure

Cellulose is a carbohydrate derived from D-glucose monomer units or so called anhydroseglucose monomer units (AUG). The six carbons in a cellulose monomer unit are numbered 1 to 6 (see figure 1). The monomers are linked through β(1→4)-glycosidic bonds and in that way it discerns from e.g. starch and other carbohydrates as these are made up α(1→4)-glycosidic bonds. On the remaining carbons three hydroxyl groups are attached that are referred to as OH-2, OH-3 and OH-6, indicating the position on the monomer unit. The repetitive group in cellulose is called cellobiose and consists of 2 AUG monomers. Each cellulose chain has two terminal end groups, of which one is reactive as it able to reduce an oxidizing functional group of a molecule, e.g. active pharmaceutical ingredient, or and therefore referred to as the reducing end.

Excipa: cellulose chemical composition characterization services, pharmaceutical excipient

Figure 1 Structural formula of Cellulose; monomers en cellobiose

Cellulose purity

In case cellulose from wood pulp is used as source, it will contain traces of lignin and hemicelluloses. Lignin is a phenolic substance consisting of an irregular array of variously bonded  hydroxy-  and  methoxy-substituted  phenylpropane  units. Hemicelluloses  are  mixtures  of  polysaccharides  synthesized  in  wood  almost  entirely  from  glucose,  mannose, galactose,  xylose,  arabinose,  4-O methylglucuronic  acid,  and  galacturonic  acid  residues. Generally,  hemicelluloses  are  of  much  lower  molecular weight  (MW) than  cellulose  and  some  are  branched.

Read our Case Study: VARIABILITY OF EXCIPIENTS: Xylose in microcrystalline cellulose

Cellulose properties

In spite of the multiple hydroxyl groups, cellulose is not soluble in water. The linear structure of the chain polymer and the equatorial conformation of the glucose residues facilitate formation of Van der Waals forces and hydrogen bonds between chains, holding the chains firmly together side-by-side and forming micro fiber-like strands with high tensile strength. The stands and chains also bundle regularly in places to form solid, stable crystalline regions that give the packed chains even more strength and stability. This semicrystallinity differentiates cellulose from starch, which chains are coiled or branched, making cellulose far more resistant to amorphization when heated in water. Whereas starch undergoes a crystalline to amorphous transition when heated beyond 60-70 °C in water, cellulose requires a temperature of 320 °C and pressure of 25 MPa to become amorphous in water. Several different crystalline structures of cellulose are known, corresponding to the location of hydrogen bonds between and within strands. Natural cellulose is “cellulose I”, while cellulose in regenerated cellulose fibers is “cellulose II”. There  are  at  least  two  other  structures  reported  for  modified crystalline  cellulose, but “cellulose II” is the most important one. It is obtained by mercerization or regeneration of native cellulose. Mercerization is treatment of cellulose with strong alkali in order to solubilise and remove lignin.  Regeneration is solubilising cellulose with strong alkali and carbon disulfide followed by a conversion back to cellulose and precipitation as regenerated cellulose. The conversion of “cellulose I” to “cellulose II” is irreversible, suggesting that “cellulose I” is metastable and cellulose II is stable. A more purified form of cellulose II has been used in the pharmaceutical industry as excipients in tablets, namely MicroCrystalline Cellulose (MCC).

Many properties of cellulose depend on its polymer chain length or degree of polymerization (DP), the number of glucose monomer units that make up one polymer molecule. The degree of polymerization depends largely on the origin of the cellulose, where cellulose from wood pulp has chain lengths ranging from 300 to 1700 glucose monomer units while cotton and other plant fibers have typically a molecular length equal to 800 – 15,000 monomer units. The variability in properties of cellulose from natural sources is in general high; the average degree of polymerization might vary significantly just like the polydispersity of the distributions.

Cellulose can be solubilised by disrupting of the crystalline structure. This can be achieved using specific solvents or by chemical modification of the cellulose. See also Hypromellose.

Be in control of your product!

Feel free to get in touch with our experts to characterize your cellulose and see how we can help you in making your products safe, robust and stable.

Welcome to Excipia, a service platform dedicated to the composition, quality and quantity of excipients in medicinal products.

Discover our unique services such as quantitative excipient analysis, identification, selection or specific formulation development support. Don’t forget to check out our case studies.

Try us. Feel free to contact us using the form below or by sending a message to Excipia@avivia.nl.

Menno Wiltink
Founder of Excipia.


Cellulose Characterization Services

Excipia is an independent contract service platform that focuses on the physicochemical characterization of pharmaceutical excipients and food ingredients like cellulose; as a pure substance, as a raw material or when processed into end products.

More than 25 years in the development of pharmaceutical formulations have taught us that the limited information available on an excipient Certificate of Analysis (CoA) often falls short of explaining observed product or excipient characteristics and that more in-depth knowledge of the actual chemical excipient composition is essential to meet and understand specific formulation challenges.

Over the past 15 years, Excipia analytical scientists have spent tens of thousands of hours establishing unique, specific analytical and physicochemical methods with ingenious sample preparation techniques to characterize cellulose ans other pharmaceutical excipients.

In these years we have gained a lot of knowledge about many excipients, their properties and exact composition, the difference between batches, qualities, grades, and manufacturers, how to quantify them in medicines and how they can best be used in a formulation.

Excipia offers fast and flexible hands-on cellulose characterization services to reveal and compare hidden cellulose properties like:

    • the presence of potential reactive cellulose impurities or functional groups,
    • reducing power of cellulose,
    • cellulose degradation products and related substances,
    • cellulose molecular weight distributions,
    • and many other cellulose characteristics.


In addition, Excipia can help users of cellulose to pick the most appropriate cellulose manufacturer, select the most suitable cellulose grade for their finished dosage form, or define customized cellulose specifications to control product performance, quality and safety.

Trust Excipia for Exceptional Excipient Characterization Services

With a commitment to excellence and a track record of success, Excipia is your reliable partner in excipient characterization. Contact us today to elevate the quality and performance of your pharmaceutical formulations.

Overview Cellulose
Example Analysis

Excipia, a division of Avivia BV

 Excipia as dedicated excipient knowledge platform is a division of Avivia BV, a Dutch independent specialized pharmaceutical development company that operates a hybrid business model combining CRO service activities with internal product development programs. The other complementary platforms of Avivia are Pharmaceutical R&D, Analytical R&D, and Biorelevant Dissolution Testing. For more information about Avivia and its pharmaceutical development CRO services, please visit the Avivia website.