Friability of MCC Pellets: importance in pharmaceutical formulations

In this note, the importance of friability of MCC pellets in pharmaceutical formulations shall be emphasized. Friability is commonly konwn as a parameter describing “the tendency of a solid substance to break into smaller pieces under stress or contact” [1].

Microcrystalline cellulose (MCC) pellets are spherical, multi-particulate carriers widely used in modern pharmaceutical formulations, particularly for the development of oral solid dosage forms. Produced typically via extrusion-spheronization, MCC pellets offer a highly versatile platform for drug delivery, supporting both immediate and modified-release applications. Their unique physico-chemical properties make them a preferred choice in high-performance formulations.

One of the primary advantages of MCC pellets lies in their exceptional quality and mechanical robustness, especially their low friability. Low friability indicates a strong resistance to mechanical stress during handling, coating, blending, packaging, and transport. This property is essential for maintaining the structural integrity of pellets throughout the manufacturing process. Inconsistent or fragile pellets can lead to attrition and dust formation, which not only poses challenges to process efficiency but also risks compromising the uniformity of drug content and release profiles.

Another critical characteristic of MCC pellets is their narrow particle size distribution. Uniform pellet size ensures consistent flow behavior and predictable packing density, which are fundamental for reliable downstream processes such as capsule filling and tablet compression. Moreover, a uniform size distribution is vital for achieving consistent drug release kinetics, particularly when functional coatings are applied. Variability in pellet size can result in uneven coating thickness, leading to non-uniform dissolution rates and reduced therapeutic performance. We shed some light on issues arising from wide size distribution levels in this application report.

Friability deviations might cause issues

If friability of MCC pellets is not good (i.e., high friability levels), it means the pellets show risk to breaking or crumbling under mechanical stress during handling, processing, or transport. This can have several negative effects on the pharmaceutical formulation. We focus on main 6 negative effects:

  • Loss of pellet integrity

    • Pellets may break into smaller fragments or powder, affecting the uniformity of particle size during production cycles.
    • This can lead to inconsistent coating processes and thus drug release profiles, especially in modified-release formulations.

  • Content uniformity issues

    • If the active pharmaceutical ingredient is loaded onto the pellets, fragmentation can cause segregation of the active.
    • This results in dose variability, compromising safety and efficacy.

  • Poor flowability

    • Fragmented or powdered material tends to flow poorly, which complicates downstream processes like capsule filling or tableting.
    • Potential variations in rheological flow behavior need to be examined in risk analysis studies.

  • Dust generation

    • High friability leads to more dust by material detachment, which is problematic for handling safety, equipment contamination, and environmental control in manufacturing.

  • Coating problems

    • In pellet-coated systems (e.g., for enteric or sustained release formulations), broken pellets may receive uneven coating, impacting release kinetics and protection from gastric environment.
    • In worst case, a drug-coated pellet break during uptake, causing increased risk of sudden dose dumping

  • Compression Issues

    • If pellets are compressed into tablets, high friability can affect tablet hardness, disintegration, and mechanical stability.
Friability of MCC Pellets

Conclusion

Together with further physical and chemical parameters, the low friability of MCC pellets contributes to an enhancement in formulation reproducibility, improved product stability, and compliant drug formulations. These qualities are particularly important in advanced drug delivery systems, where precise control over release profiles, dosage uniformity, and process scalability is required. As such, CELLETS® represent a high-value excipient platform for pharmaceutical manufacturers in formulation development.