MicroCrystalline Cellulose (MCC)

Microcrystalline cellulose is a more purified form of Cellulose. It is a white, odorless, tasteless carbohydrate polymer powder that typically consists of up to 350 glucose units. Humans are unable to digest microcrystalline cellulose, making it Generally Recognized As Safe (GRAS) for human consumption. This, and its lack of odor and taste give it a great use as a thickener, stabilizer or excipient for any food product or pharmaceutical tablet.

Cellobiose structure of pharmaceutical cellulose excipient

Figure 1 Cellobiose, the polymeric structure of cellulose

Processed cellulose already contains partly crystalline segments but also weaker amorphous regions. In microcrystalline cellulose, the crystalline regions of cellulose have been isolated, forming a more crystalline product. It can be made of any material that contains high volumes of cellulose; which is found in cell walls in plants. This abundance in nature makes it cheap to produce. The level of crystallinity is higher when the polymer is extracted from cotton compared to other sources. However, wood is used mainly in pharmaceutical applications due to its abundance and lower price. Beside these two advantages, the possibility that cotton is genetically modified (GM) deters many companies.

Read more below about the composition, production, variability and purity of microcrystalline cellulose, MCC properties and microcrystalline cellulose characterization.

Look here for information about hypromellose.

Microcrystalline Cellulose Characterization Services

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

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

In addition, we can help users of MCC to pick the most appropriate microcrystalline cellulose manufacturer, select the most suitable microcrystalline cellulose grade for their finished dosage form, or define customized microcrystalline cellulose specifications to control product performance, quality and safety.
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Microcrystalline cellulose has strong intra- and intermolecular binding patterns caused by hydroxyl groups, which cause the polymer to be partly crystalline, mechanically stable, stiff and hard to dissolve. Special solvents are therefore utilized to dissolve cellulose. Low molecular mass cellulose chains are dissolved instantly while higher molecular mass polymers are more difficult to dissolve and require an activation step. The exact mechanisms for the dissolution process of microcrystalline cellulose are not clearly known.

Different suppliers of MCC exist, each with their own product and brand that differs from one another. Although there is no general system for assigning different grades, most manufactures indicate the particle size and moisture content by using numbers. The most common numbers are 101, 102, 200, 301 and 302. The first digit usually indicates a certain density, while the last two digits describe a certain particle size and moisture content combination. However, not all suppliers use this system and may deviate of such. Other letters are sometimes added to indicate an extra step added to the production process. These can consist of properties such as a different drying technique or granulation.

Microcrystalline cellulose composition and production

The manufacturing process for microcrystalline cellulose from wood material has been known for over 60 years. Wood consists of lignin (18-35%), cellulose and hemicellulose (65-75%). Lignin is a phenolic substance consisting of an irregular distribution of variously bonded hydroxyl- and methoxy-substituted phenyl propane units. Together with cellulose it provides a structural function inside plants. It also allows transport of water inside the vascular tissues of plants cells better then hemicelluloses and celluloses due to its lesser hydrophilic properties. Hemicelluloses are supporting polymers and are present in cell walls in the range of 25% to 35%, depending on the plant type. It consists almost entirely from monosaccharides such as glucose, mannose, galactose, xylose, arabinose as well as 4-O methylglucuronic acid and galacturonic acid residues. Unlike (microcrystalline) cellulose, the hemicelluloses are branched, causing them to be mostly amorphous. The chemical composition of hemicellulose may differ depending on the type of wood chosen for production. The woody material of some softwood species, such as Norway’s spruce, can contain up to 20% galactoglucomannans. These are hemicelluloses made primarily of galactose, glucose and mannose. Hardwood species such as conifers contain mostly glucuronoxylans, which are consist out of glucuronic acid and xylose as its main constituents. Reports show that the country of origin can have significant impact on properties such as crystal structure and particle size. These differences can have a further influence on rheological behavior, which can cause difficulties in certain pharmaceutical processes, like tabulation.

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

Excipia: hemicellulose in pharmaceutical cellulose excipient

Figure 2  Xylose, Glucose, Galactose, Arabinose and Mannose in their pyranose form.

Microcrystalline cellulose is difficult to purify without increasing degradation products during processing. The general MCC manufacturing process is partially like that of the production of cellulose and starts with chopping up wood into small particles. The woodchips undergo first a pulping process: they are hydrolyzed under heat and pressure by mineral acid or bases. Ordinary pulping processes (Kraft process) can be performed using a mixture of sodium hydroxide and sodium sulfide (NaOH and Na2S) that break the bonds of lignin to cellulose. Another pulping method is sulphite pulping, where with various salts or sulphurous acid (mostly sodium bisulphate NaHSO3 or sodium sulphate Na2SO3) to extract and remove the lignin from the wood pulp. Hydrolysis converts insoluble hydroxides, oxides and sulfonates into soluble compounds. Thereafter, alkaline treatment may be performed with a solution of NaOH at high temperatures (around 100 °C) to remove hemicelluloses.

In the processes amorphous regions of the cellulose are broken up simultaneously, while leaving the crystalline segments intact. The hydrolysation is carried out until a certain level of polymerization is achieved. After hydrolysation the material is washed with water, which removes the soluble impurities, but leaves the insoluble crystalline cellulose. After filtration the resulting cake is resuspended in water and spray dried with hot gas. This spraying process can be taught of as breaking down the cellulose fibrous material to a microcrystalline form and then agglomerating these crystallites into particles. Although likely all the lignin is removed during the dissolution and filtering process, some hemicellulose might still be present in the purified powder. In some purification processing the pulp is additionally treated with an aqueous chlorine solution and bleached with NaClO8.

The above mentioned production process is a general method for production; manufactures can utilize different chemicals or production steps to add specific functionality to their product.

Microcrystalline cellulose purity and degradation products

After processing of the wood pulp, microcrystalline cellulose is essentially free of fibrous cellulose. Potential impurities in MCC consist of substances common in the raw materials, including traces of lignin, hemicelluloses, oxycelluloses, furans and water. Atmospheric oxygen, and if present, peroxides and chlorous acids, can easily oxidize and form oxidized cellulose. Oxidized cellulose consists of glucose units where the primary alcohol groups have been converted to e.g. carboxyl or carbonyl groups. Formation of oxycellulose can cause degeneration of the cellulose backbone. During the purification process, both hot alkaline and acid solutions can be applied. These extreme conditions are optimal for the formation of additional unwanted reactive degradation products like organic acids, e.g. formic acid, acetic acid and butyric acid, and furans such as Hydroxy Methyl Furfural (HMF) and Furfural. Furans, oxycellulose, cellulose reducing end groups and linear shaped monosaccharides are able to form new products by Maillard reactions.

Microcrystalline cellulose variability

Because microcrystalline cellulose is purified and produced by different manufactures, process technology, process parameters and even operator actions may contribute to batch-to-batch inconsistency. Production facilities are located all over the world and may use local tree species that differ in chemical composition. Variability is introduced by inadequate and fluctuations in specifications of starting materials; species of crop, seasonal and different regional provenance can have a remarkable impact. The amount hemicelluloses and lignin can differ in the same tree population; trees in the middle of the woods, edge of the forest, sunny side, wind side, ect. This can result in batch to batch variation within the same manufacturer and grade and influence the reactivity of microcrystalline cellulose with active pharmaceutical ingredients in pharmaceutical formulations.

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

Microcrystalline Cellulose Characterization Services

Excipia is an independent contract service platform that focuses on the physicochemical characterization of pharmaceutical excipients and food ingredients like microcrystalline 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 microcrystalline cellulose characterization services to reveal and compare hidden microcrystalline cellulose properties like:

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


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

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.