Unlock your drug’s potential with MCC: Explore three modern uses for this trusted excipient

In this blog, Yeli Zhang, Ph.D., Senior Lead Applications Scientist at IFF Pharma Solutions, explores how this time-tested excipient can go beyond its traditional roles to address modern formulation challenges and support the development of increasingly complex drugs, using Avicel® as an example. Read on to uncover three ways you can harness the tried-and-true properties of MCC: including (1) protecting heat-sensitive actives with moisture-activated dry granulation (MADG), (2) advancing continuous manufacturing for greater efficiency, and (3) mitigating risk of nitrosamine formation.

1. Unlock the potential of MADG for heat sensitive actives

Many of today’s most in-demand active pharmaceutical ingredients (APIs) are sensitive to heat, such as biologics, peptides and lipid-based molecules. This sensitivity makes traditional wet granulation processes for forming powder granules unsuitable, as it involves a drying step that exposes ingredients to high temperatures. MADG offers an effective solution by eliminating the need for heat drying. Instead, it creates granules through a process that uses a liquid binder, protecting heat-sensitive APIs from thermal degradation. But how does MCC fit into this equation? Yeli explains:

“MADG needs coarse, free-flowing and water-absorbent excipients that match the wet granule morphology and bind free water. Large particle grades of MCC with low moisture content, such as Avicel® PH-200 LM, are ideal candidates for this process. Why? Because MCC excipients can absorb extra water during the granulation process, binding it away from other ingredients in the formulation. This water-binding property is also why MADG doesn’t require a drying step, making Avicel® MCC a key player in protecting sensitive APIs from elevated temperatures.”

1. Increase efficiency of continuous manufacturing

Continuous manufacturing has become a competitive advantage and a common tool used by agile companies in the evolving pharma industry. Continuous processes offer several benefits, including reduced manufacturing times, improved drug product quality, flexible batch sizes, simplified scaling, greater control over critical process parameters, less energy consumption and reduced costs.[1] Despite these advantages, adopting continuous manufacturing processes comes with its own set of unique challenges.

For instance, ensuring that the continuous feeding of materials is achieved with consistently high accuracy and low variability is critical for maintaining content uniformity in solid dosage forms like tablets. This is where selecting the right excipients at the optimal feeding rates becomes essential. Yeli expands on this:

“We’ve investigated the outcome of using Avicel® MCC with different particle sizes and feed rates on variability in a loss-in-weight twin screw continuous feeder.​[2] The feed rate is the speed at which materials, such as excipients and active ingredients, are discharged from the feeder. We found that the feed rate had a big impact on feeding variability, with higher feed rates resulting in lower variability (within the rate range that we studied). For instance, at a 3.75 kg/h feed rate, a 100 µm MCC grade showed variability around 6.2%. When the feed rate increased three-fold, variability dropped by half (to 2.25–3%). At a 25 kg/h feed rate, variability decreased further to just 1–1.5%. These trends were consistent across other MCC grades, including Avicel® PH 105 µm, 102 µm, and 200 µm. It is therefore beneficial for drug developers to use a higher feed rate, regardless of MCC particle size, to minimize variability during continuous manufacturing—enhancing efficiency and quality while lowering costs. In cases where increasing the feed rate is not possible or desired, we also found that changing the particle size of MCC at the lowest feed rate can reduce the variability of the feed; however, this difference diminishes as the rate increases from 3.75 to 25 kg/h.”

1. Reduce risk of nitrosamine formation with low nitrite MCC

Since 2018, potentially harmful nitrosamine contaminants have been found in several drug products. This includes common drugs like angiotensin II receptor blockers (ARB) used to treat hypertension, metformin for diabetes and ranitidine for stomach acid-related problems. Ever since, drug manufacturers have faced the difficult task of assessing, controlling, and minimizing nitrosamine impurities in their formulations and across the entire drug supply chain. This is a significant challenge given that nitrosamine impurities can be introduced into drug products through multiple routes. One such pathway occurs when an API containing a vulnerable amine reacts with nitrite under certain conditions, leading to the formation of API-based nitrosamines.[3] Nitrites are found commonly in nature making them difficult to avoid.[4] This is important to be aware of when using excipients derived from natural, raw materials, such as MCC.[5] Research reveals that MCC from different excipient suppliers can contain between 0.04 to 2.4 µg/g of nitrites.⁵ Yeli shares some key considerations:

“Choosing low nitrite MCC, like low nitrite Avicel®, is one tool that may help drug developers address this modern formulation challenge. Manufacturers can trust the science-backed benefits of low nitrite excipients with research confirming that they can successfully reduce nitrosamines in model formulations by up to nearly 10-fold compared to excipients with average levels of nitrites.[6] In addition, low nitrite MCC excipients are compatible with various APIs and can easily be used alongside other mitigation strategies such as nitrite scavengers, helping drug developers achieve holistic nitrosamine prevention.[7] At IFF Pharma Solutions, we use proprietary analytical methodology to ensure that our low nitrite Avicel® MCC meets the specification on the certificate of analysis. We were the first company to provide this for low nitrite MCC. We also performed comparability studies to demonstrate that our low nitrite Avicel® portfolio is comparable in performance to our original Avicel® excipients.”

Achieve formulation excellence with Avicel®

By leveraging the unique properties of specific grades of MCC, drug developers can tackle fresh formulation challenges with confidence—whether it’s protecting moisture-sensitive APIs through MADG, reducing variability in continuous manufacturing, or minimizing nitrosamine contamination risks. At IFF Pharma Solutions, we offer Avicel® MCC in a wide range of grades with different particle sizes, moisture content, and bulk density, plus low nitrite versions, to help drug manufacturers achieve formulation excellence.

Want to know more? Download our guide to explore the full potential of our Avicel® MCC portfolio.

[1] Tulip. Pharma 4.0. What is Continuous Manufacturing? A Guide for Pharmaceutical Manufacturers. April 2022. Available at: https://tulip.co/blog/continuous-manufacturing/

[2] AAPS Poster: Elizabeth Tocce, Sharon Nowak, Kevin O’Donnell, Yeli Zhang, Lewis Cesarano (2023). Impact of microcrystalline cellulose particle size grade on loss-in-weight continuous feeding​.

[3] Moser J, Ashworth IW, Harris L, Hillier MC, Nanda KK, Scrivens G. N-Nitrosamine Formation in Pharmaceutical Solid Drug Products: Experimental Observations. J Pharm Sci. 2023 May;112(5):1255-1267.

[4] Control of Nitrosamine Impurities in Human Drugs (2021). Guidance for the Industry. FDA. Available at: download (fda.gov)

[5] Boetzel R, Schlingemann J, Hickert S, Korn C, Kocks G, Luck B, Blom G, Harrison M, François M, Allain L, Wu Y, Bousraf Y. A Nitrite Excipient Database: A Useful Tool to Support N-Nitrosamine Risk Assessments for Drug Products. J Pharm Sci. 112(6):1615-1624 (2023).

[6] Berardi, A., Jaspers, M., & Dickhoff, B. H. J. (2023). Modeling the Impact of Excipient Selection on Nitrosamine Formation Towards Risk Mitigation. Pharmaceutics, 15(8), 2015.

[7] Bayne AV, Misic Z, Stemmler RT, Wittner M, Frerichs M, Bird JK, Besheer A. N-nitrosamine Mitigation with Nitrite Scavengers in Oral Pharmaceutical Drug Products. J Pharm Sci. 2023 Jul;112(7):1794-1800.