Roller compaction: Size distribution during different stages of the product pathway using three types of lactose

Abstract

Roller compaction is a widely applied dry granulation technique in the pharmaceutical and food industries, valued for its scalability, energy efficiency, and suitability for moisture- and heat-sensitive materials. This study investigates the evolution of Cumulative size distributions (CSDs) of three pharmaceutical-grade lactose types (α-lactose monohydrate (Volactose), spray-dried lactose (SD), and anhydrous lactose (21AN)) as they processed by roller compaction under varying hydraulic pressures. CSDs data collected at the product pathway (the Roller, Flake Crusher, Upper Mill, and Lower Mill) were analysed using the two-parameters of Weibull equation.

Highlights

Weibull distribution effectively characterised particle size evolution during roller compaction across all process stages.
Increasing hydraulic pressure significantly increased characteristic particle size (x₀) and narrowed particle size distribution (higher n).
Progressive fragmentation along the product pathway reduced particle size and enhanced distribution uniformity.
Milling stages showed improved model accuracy due to more homogeneous granule populations.
Distinct breakage mechanisms identified: impact-dominated fragmentation in flake crushing and combined impact–shear in milling.
Weibull shape parameter (n) demonstrated strong potential as an indicator of process-induced homogenisation.
Findings support future integration into Population Balance Models with real-time process monitoring for dry granulation control.

The results demonstrate that the Weibull equation effectively describes the cumulative particle size distributions, particularly at the milling stages where narrower distributions were observed and the coefficient of determination (R²) typically exceeded 0.96. Increasing hydraulic pressure resulted in larger characteristic particle sizes (x₀) due to enhanced inter-particle bonding during compaction. Conversely, progressive size reduction was observed along the product pathway, with decreasing x₀ values as the material underwent fragmentation in the flake crusher and subsequent milling stages. The Weibull shape parameter (n) increased with increasing hydraulic pressure, indicating narrower particle size distributions, while the milling stages promoted further homogenisation of particle size.

Microscopic surface profiling revealed that fragmentation mechanisms vary across processing stages. The flake crusher stage is primarily governed by impact-driven breakage, whereas the Rotor-Fine-Granulator (RFG) milling stage involves a combination of impact and shear forces generated by the impeller–screen interaction. These mechanisms lead to progressive particle fragmentation and increasing fines generation throughout the process. Despite differences among the lactose types, similar particle size evolution trends were observed, indicating that the size reduction behaviour is largely governed by the roller compaction process itself.

Overall, the study demonstrates that the Weibull distribution provides a robust statistical framework for analysing particle size evolution in roller compaction systems and highlights the combined influence of compaction pressure and downstream milling on granule size characteristics.

Continue reading here

Materials

Three industrially relevant lactose powders were selected: α-lactose monohydrate (Volactose, Volac Ltd., UK), spray-dried lactose (Excipress SD2L, Armor Pharma, France), and anhydrous lactose (SuperTab21AN, DFE Pharma, Germany). Each powder was conditioned at 35% relative humidity (RH) and 20 °C for 72 hours in a Memmert IN110 humidity chamber to minimize variability in moisture content.

Mohamed N. Badri, Riyadh B. Al-Asady, Manfred Felder, Agba D. Salman, Roller compaction: Size distribution during different stages of the product pathway using three types of lactose, Chemical Engineering Research and Design, Volume 229, 2026, Pages 447-463, ISSN 0263-8762, https://doi.org/10.1016/j.cherd.2026.04.017.