Soft Tabletting of Pellets into Multiple Unit Pellet Systems (MUPS): Introduction and Scientific Summary

Introduction

Soft tabletting of pellets is a specialized pharmaceutical compaction technology preserving coated pellet integrity during tablet compression. It combines coated pellet subunits with cushioning excipients and compresses them into tablets without functional damage. This technology underpins Multiple Unit Pellet Systems (MUPS), where tablets disintegrate into individually coated pellets in the gastrointestinal tract. MUPS leverage multiparticulate advantages including uniform gastrointestinal transit, reduced dose dumping risk, and improved bioavailability. They also retain tablet manufacturing efficiency and patient convenience compared with traditional capsule dosage forms. Pellets composed of microcrystalline cellulose are ideal for MUPS due to plastic deformation and excellent flow. MCC pellets function as drug cores and cushioning agents, protecting pellet coatings during compression. Commercial MCC pellets, often marketed as CELLETS®, enable consistent drug layering and maintain pellet integrity. They improve tablet mechanical strength and promote rapid disintegration in final MUPS formulations. MUPS tablets provide patient benefits including reduced esophageal adhesion, divisibility, and consistent drug release. These advantages outperform monolithic tablets in safety, flexibility, and controlled release performance.

Summary of the Publication: Soft Tabletting of MCC 102 and UICEL-A/102 Pellets into Multiple Unit Pellet Systems

The dissertation by V. Balzano investigates soft tabletting of MCC 102 and UICEL-A/102 pellets for effective MUPS dosage forms. It examines interactions between pellet formulation, coating integrity, and compaction processes influencing MUPS performance. The study highlights the need to balance tablet mechanical strength with rapid pellet release after ingestion. This balance preserves pellet dissolution profiles, coating functionality, and consistent bioavailability.

Two cellulose polymorphs, MCC 102 (Cellulose I) and UICEL-A/102 (Cellulose II), were evaluated as pellet cores and cushioning excipients. Sodium diclofenac served as a model drug, and pellets were coated with Kollicoat® SR 30D. Homogeneous extruded pellets were compared with inhomogeneous pellets produced by dry powder layering. Inert starter cores included CELLETS® and Suglets®. Both pellet types formed MUPS tablets with acceptable mechanical strength of 70–100 N. Tablets showed rapid disintegration within three minutes. Dissolution profiles and pellet microstructure closely matched those of uncompressed pellets.

The dissertation by V. Balzano [1] on soft tabletting of MCC 102 and UICEL-A/102 pellets investigates the complex interplay between pellet formulation, coating integrity, and the compaction process required to produce effective MUPS dosage forms. The study recognizes that MUPS tablets must achieve a delicate balance between mechanical robustness and the ability to rapidly release and disperse individual pellet subunits after ingestion. This is essential to preserve the original dissolution profile and functional coating of the pellets, which in turn supports consistent bioavailability and therapeutic performance.

Two Cellulose Types Play a Main Role

The research highlighted differences between the two cellulose types: UICEL-A/102 pellets were generally more porous and less spherical but demonstrated faster dissolution, attributed to their greater swelling capacity. This made UICEL-A/102 favorable for immediate-release applications, whereas MCC 102 provided more controlled-release characteristics due to better retention of pellet features after compaction. For inhomogeneous pellets, UICEL-A/102-based MUPS maintained adequate robustness and timely disintegration (≤ 12 min), whereas MCC 102-based MUPS were overly compacted and disintegrated slowly (> 50 min), unsuited for rapid release. The choice of starter core also influenced performance: pellets with MCC cores (CELLETS®) showed better retention of release profiles compared to those with Suglets®, suggesting that the plastic behavior of MCC contributes to softer compaction and less coating damage.

Overall, the multifactorial investigation revealed that the proportion of pellet core material, type and quantity of filler/disintegrant, and pellet production method critically influence disintegration and dissolution outcomes. While UICEL-A/102 excelled as both filler and disintegrant in immediate-release MUPS, its suitability for extended-release formulations was limited due to its intrinsic swelling and porosity. Conversely, MCC 102 provided a balanced profile for controlled-release systems.

Scientific Insights: CELLETS®, Take-Home Messages, Challenges, and Material Effects

In this study, CELLETS® served as neutral starter cores in the dry powder layering process, acting as foundational substrates upon which drug–excipient layers were built. Their use significantly impacted the softness of compaction, with MCC cores contributing to less elastic deformation and reduced coating damage compared to other core types such as Suglets®. This underscores the importance of MCC pellet characteristics in achieving optimal MUPS performance.

The key take-home messages include the necessity of balancing pellet composition, excipient selection, and compaction parameters to deliver robust tablets that disintegrate rapidly without altering dissolution behavior. UICEL-A/102 may be advantageous for immediate release due to its swelling and porous nature, while MCC 102 remains superior for controlled release applications due to its plasticity and retention of pellet integrity. However, producing MUPS with coated pellets remains challenging because of the risk of coating fracture and altered release profiles under compression.

Optimizing Pellet Porosity and Sphericity

Obstacles for MCC pellets include optimizing porosity and sphericity to reduce deformation and friability during compaction. Pellet hardness must be balanced to ensure mechanical strength without impairing rapid tablet disintegration. Opportunities include engineering MCC excipients with tailored deformation and cushioning properties. Advanced starter bead designs, such as optimized CELLETS® morphologies, offer further performance improvements. Predictive formulation models can integrate pellet properties, filler behavior, and compaction dynamics.

Pellet sphericity, friability, and hardness are critical determinants of performance. Higher sphericity enhances flowability and uniformity in tableting, reducing segregation. Lower friability indicates that pellets are less likely to fracture or release fines during manufacturing, preserving coating integrity. Hardness must be finely tuned: insufficient hardness yields weak tablets, whereas excessive hardness can suppress disintegration and compromise drug release. Optimal values for these physical attributes facilitate the “soft tabletting of pellets” that preserves functional coatings and ensures consistent therapeutic outcomes.

Conclusion and Outlook

Soft tabletting of pellets into MUPS is a technically demanding yet beneficial pharmaceutical strategy combining multiparticulate delivery with tablet convenience. Research shows that controlling pellet formulation, excipient selection, and compaction parameters is essential for desired disintegration and release profiles. Key formulation factors include MCC type and starter cores such as CELLETS®. Challenges remain, particularly coating integrity and mechanical stress during tabletting. Advances continue through materials innovation, process optimization, and tailored excipient design. Future research will focus on engineered cushioning layers, predictive compaction modeling, and novel MCC pellet formulations.

References

[1] Dissertation, Balzano, Vincenzo; doi: 10.5451/unibas-004872301.