Strategies and research progress of roller compaction process in dry granulation scale-up process

Abstract

Roller compaction dry granulation is one of the pivotal dry granulation technologies in solid dosage form manufacturing, offering irreplaceable advantages in processing heat-sensitive or moisture-sensitive materials. With the advancement of large-scale production and intelligent manufacturing in the pharmaceutical industry, the scale-up challenge of roller compaction dry granulation from laboratory-scale to industrial-scale production has gradually emerged as a critical bottleneck restricting its widespread application. During the scale-up process, the complex coupling effects among parameters such as compaction force, roller gap, roller speed, and material properties can induce significant alterations in particle quality attributes (e.g., particle size distribution, solid fraction), thereby compromising product consistency and production efficiency.

In recent years, emerging research efforts, including model-based scale-up approaches, the Johanson model, numerical simulation, and data-driven optimization strategies, have been continuously advancing. These endeavors have played a proactive role in unraveling the mechanistic correlations during scale-up and establishing predictable scale-up models. This review systematically expounds on mechanism-driven scale-up methods (e.g., those based on the Johanson model and numerical simulation), integrates the latest research progress in the application of simulation technologies, and clarifies the core principles and implementation strategies for process scale-up. It aims to provide theoretical guidance and practical references for the robust scale-up and industrial production of the roller compaction dry granulation process.

Introduction

Dry granulation is an important powder processing and granulation technique in the pharmaceutical industry. In this process, powders are compacted into ribbons, which are then subjected to milling and sieving to produce granules of suitable particle size for subsequent tableting or capsule filling(Hwang et al., 2019, Mohylyuk, 2022, Perez-Gandarillas et al., 2016, Wen et al., 2025, Jin et al., 2019). Dry granulation can be mainly categorized into slugging dry granulation and roll compaction dry granulation, among which roll compaction dry granulation is more commonly employed. Therefore, roll compaction dry granulation is the focus of discussion in this paper.

Owing to its advantages of solvent-free operation, no drying step, and simple procedure, dry granulation has become one of the preferred technologies for handling thermosensitive and moisture-sensitive drugs(Egbu et al., 2018, Sauer et al., 2021). This process can not only significantly improve the flowability and compressibility of active pharmaceutical ingredients (API), but also plays a critical role in the preparation of High drug loading formulations and ensuring content uniformity of pharmaceutical products (Bai et al., 2021, Johanson, 1965).

Scale-up of the dry granulation process is a key step for the industrial translation of dry granulation technology and an indispensable pathway to realize its application value. A rational scale-up strategy is not only related to the consistency and controllability of ribbon and granule quality, but also directly affects production efficiency, cost control, and product quality stability, which is of great significance for guaranteeing the feasibility and reliability of industrial pharmaceutical manufacturing.

However, variations in equipment structure, roll size, and operating parameters often lead to nonlinear changes in the stress and densification behavior of materials during dry granulation. The complex interactions among scale-up parameters and the diversity of material properties in roll compaction dry granulation, together with the lack of unified scale-up criteria, result in considerable challenges in dry granulation scale-up and insufficient research progress in this field (Guigon and Simon 2003).

With technological advancements and an in-depth understanding of dry granulation, the scale-up strategies for dry granulation are gradually shifting from empirical-driven to mechanism-driven approaches, and remarkable progress has been made in scale-up research. Nevertheless, systematic summaries or review articles are still lacking. This paper reviews the core theories and key technologies for the scale-up of roll compaction dry granulation, and systematically explores feasible scale-up pathways, aiming to provide references for the robust scale-up and intelligent manufacturing of dry granulation processes.

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Likun Zhou, Tongyao Xie, Yiyao Wu, Yu Zhao, Yaguang Yang, Kaiyi Song, Yajing Wang, Dongli Qi, Strategies and research progress of roller compaction process in dry granulation scale-up process, International Journal of Pharmaceutics, Volume 701, 2026, 127178, ISSN 0378-5173, https://doi.org/10.1016/j.ijpharm.2026.127178.

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