Less known facts about Excipients: Microcrystalline Cellulose (MCC)

This article is part of the “Less Known Facts About Excipients” series by Philippe Tschopp.

Microcrystalline Cellulose: A versatile binder, disintegrant and filler

Microcrystalline cellulose (MCC) is one of the most widely used pharmaceutical excipients, forming the backbone of countless tablet formulations. Yet despite its importance, many people are surprised to learn that MCC is not a naturally occurring material, it is produced by carefully modifying one of nature’s most abundant polymers.

While cellulose itself is found in virtually every plant, pharmaceutical-grade MCC is manufactured through a controlled hydrolysis process that transforms natural cellulose into a highly functional excipient with exceptional compressibility.

Microcrystalline cellulose is purified, partially depolymerized cellulose obtained by treating highly purified α-cellulose, typically derived from wood pulp. Cotton linters, which consist of almost pure cellulose, may also be used as a raw material.¹–³

Fun fact: When I started to work in the industry many people I talked to would not mainly know it by “Avicel” (American Viscose Cellulose) as discovered by chance in the early sixties. Since then a lot has changed.

How is pharmaceutical MCC produced?

The production process consists of several carefully controlled steps:

Cellulose Isolation Wood or cotton fibers are processed to isolate highly purified α-cellulose by removing lignin, hemicellulose and other naturally occurring components.
Controlled Acid Hydrolysis The purified cellulose is treated with mineral acid under carefully controlled conditions. This selectively removes the less ordered (amorphous) regions while preserving the highly ordered crystalline regions.
Purification The hydrolysed cellulose is extensively washed to remove residual acid and impurities.
Drying and Milling The purified material is spray dried or dried by other controlled methods before milling to obtain pharmaceutical grades with defined particle size, density and flow properties.¹–⁵

What makes MCC unique?

Although cellulose is naturally fibrous, controlled hydrolysis fundamentally changes its physical properties. By removing the amorphous regions, MCC becomes a highly compressible powder capable of forming strong tablets without requiring extensive granulation. Its most valuable pharmaceutical characteristics include:

Excellent compressibility
Good flow properties
High dilution capacity
Chemical inertness
Insolubility in water
Good compatibility with most active pharmaceutical ingredients

Unlike many fillers, MCC contributes directly to tablet strength while also promoting rapid disintegration through its capillary water uptake.

Pharmaceutical applications

Pharmaceutical-grade MCC is used in:

Direct compression tablets
Wet granulation
Dry granulation
Capsules
Pellet formulations
Orally disintegrating tablets (ODTs)
Multiparticulate systems¹,²

Its primary functions include:

Diluent (filler)
Dry binder
Compression aid
Disintegrant (secondary function)
Processing aid

Considerations for formulators

MCC is available in numerous grades differing in particle size, bulk density and moisture content. Selecting the appropriate grade depends on the formulation strategy, manufacturing process and desired tablet characteristics.

Although MCC exhibits excellent compatibility with most APIs, very high drug loads or highly moisture-sensitive compounds may require careful optimisation of excipient selection and processing conditions.¹–⁴

Major pharmaceutical manufacturers

Examples of established manufacturers and suppliers include:

Did you know?

Although pharmaceutical MCC is derived from wood or cotton, it contains neither lignin nor wood fibers. During manufacturing, these components are completely removed, leaving behind highly purified cellulose.

Perhaps even more remarkable is that the crystalline regions preserved during hydrolysis are responsible for MCC’s exceptional tableting performance. In other words, formulators are not compressing “wood” they are compressing one of nature’s strongest microscopic structural materials.

Not to forget – Neutral starter spheres / pellets such as Celpheres or Cellets are MCC according to the pharmacopeias but have a completely different shape and function than standard MCC grades.

By Philippe Tschopp
Philippe Tschopp writes about pharmaceutical excipients, formulation and oral drug delivery, with a focus on excipient functionality, practical formulation considerations and lesser-known material properties.

Source:

Rowe RC, Sheskey PJ, Quinn ME (Eds.). Handbook of Pharmaceutical Excipients. Pharmaceutical Press / American Pharmacists Association.
European Pharmacopoeia (Ph. Eur.). Monograph: Microcrystalline Cellulose.
United States Pharmacopeia–National Formulary (USP–NF). Monograph: Microcrystalline Cellulose.
IFF Pharma Solutions. Avicel® PH Technical Handbook and product documentation.
JRS Pharma. Vivapur® Technical Information and formulation guides.
Stamm A. Wood and Cellulose Science.
Bolhuis GK, Armstrong NA. Excipients for Direct Compression: An Update. Pharmaceutical Development and Technology.

Disclaimer

This article is based on publicly available information and industry sources at the time of writing and supported by AI. While every effort has been made to ensure accuracy, completeness, and fair representation, the author does not guarantee that all information is current, error-free, or reflective of the latest developments.

The content is provided for informational and educational purposes only and does not constitute technical, regulatory, or commercial advice. No liability is accepted for decisions made based on this material. Readers are encouraged to consult the original manufacturers and official sources to verify details before making professional or business decisions.