Comparison of Shear and Fluidized Bed Granulation Using the Morphologi System: A Particle-Level Characterization Approach

Introduction

A granule is an agglomerate of primary powder particles bound together by a binder to form a larger, multiparticle entity. This production process is known as granulation, and it is widely used in pharmaceutical engineering, particularly for the manufacture of tablets, pellets, and spheronized products. Granulation is performed for several reasons. One major purpose is to prevent segregation within a blended powder mixture that arises from differences in particle size or density. Additionally, many pharmaceutical powders are cohesive and exhibit poor flow due to their small particle size, irregular shape, or surface characteristics. Converting such powders into granules produces larger particles with a more controlled size and shape, contributing to improved bulk flow properties.

In the pharmaceutical industry, wet granulation and dry granulation are typically employed. Wet granulation is more commonly used because granules can be produced efficiently through the addition of a binder solution to a powder bed. Typical wet granulation processes include high-shear granulators (impeller-type or twin-screw) and fluidized bed granulators. The selection of granulation method depends on the intended purpose and performance requirements of the final product. Because granule characteristics strongly influence the behavior of solid dosage formulations, understanding particle-level properties is essential.

Particle morphological investigation using the Morphologi 4 offers a powerful approach for studying granulation mechanisms through detailed particle characterization. This application note presents a comparative study of two types of granules—those produced using a shear granulator and a fluid bed granulator—using Morphologi 4 as an analytical platform.

Materials and Methods

The formulation components used in this study are listed in Table 1. Granule samples were produced using a high-speed shear granulator (SG) and a fluid bed granulator (FG), described in Table 2, with identical formulations. All granulation processes were performed at Towa Pharmaceutical Co., Ltd., our collaborative partner.

The Morphologi 4 was used for automated image analysis with a 2.5× objective lens in diascopic (transmittance) mode. The SDU parameters were as follows: sample volume 33 mm³, dispersion pressure 1.0 bar, injection time 20 ms, and settling time 180 s. The measurement area radius was set at 48 mm. To remove touching particles, a solidity filter (<0.9) was applied as an initial data preprocessing step. More than 40,000 particles were analyzed in each sample for comparative evaluation.

Table 2. Comparison between FG and SG process.

Comparison Item	Fluidized Bed Granulation (FG)	High-speed Shear Granulation (SG)
Schematic diagram
Principle of Granulation	Powder is fluidized by heated air, and binder solution is sprayed to induce adhesion and agglomeration.	Particles are kneaded and densified by the shear force and compressive action generated by high-speed rotating blades (agitator).
Granule Properties	Porous and lightweight; particle size tends to be uniform.	Dense and heavy; granules are hard with high mechanical strength.
Drying Process	Drying can be performed simultaneously with granulation.	Requires a separate drying step.
Advantages	Mixing, granulation, and drying can be completed in a single unit; suitable for automation.	Short processing time and relatively compact equipment.
Disadvantages	Equipment tends to be large, and countermeasures against fine-powder dispersion are necessary.	Frictional heat is easily generated, so heat-sensitive materials require careful handling.

Results and Discussion

Overall particle size (Circular Equivalent (CE) diameter) distributions are shown in Fig. 1(a) and (b), and Table 3. The FG sample contained a larger population of fine particles (number-based), whereas its volume-based distribution was narrower than that of the SG sample. The SG granules likely underwent greater compaction and compression due to mechanical agitation, which may also contribute to the broader size distribution observed. Wear from particle–particle friction during shear granulation may additionally explain this broadening.

For shape analysis, particles larger than 100 µm—which dominate the bulk volume—were selected. The proportion of these volume-dominant particles was FG = 89% and SG = 98%. High Sensitivity (HS) circularity distributions for particles >100 µm are shown in Fig. 2, with representative images of particles with a CE diameter around 200 µm shown in Fig. 3(a) and (b). The FG granules exhibited a clearly more irregular shape.

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(b)

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(b)

Granulated powders generally exhibit high flowability. To quantify flow properties with high sensitivity, Basic Flowability Energy (BFE) was measured using an FT4 Powder Rheometer (Freeman Technology) in the 25 mm blade test mode. This method enables characterization of multiple flow-related parameters derived from the specific blade stress test, with the results summarized in Table 4 and Fig. 4.

The measured BFE values were FG = 153 mJ and SG = 253 mJ, indicating that FG granules were approximately 1.6 times more flowable than SG granules. The most noteworthy aspect of these results lies in the Stability Index (SI) and Flow Rate Index (FRI). SI quantifies the degree to which flow energy fluctuates during consecutive BFE measurements; values closer to 1.0 indicate greater stability, with minimal effects from hysteresis, particle fragmentation, or agglomeration. In contrast, FRI reflects the sensitivity of flow energy to changes in tip speed. Higher FRI values indicate greater variation in flowability at lower flow velocities, a behavior typically observed in highly cohesive powders.

Interestingly, despite identical SI and FRI values for both powders, only the Total Energy differs. This indicates that although the two powders exhibit an almost identical response behavior to external displacement, their fluidity differs by approximately a factor of two.

A plausible explanation for this phenomenon is that the irregular morphology of FG granules reduces interparticle consolidation because of their smaller contact areas. However, the elevated values observed for SG samples may instead reflect more efficient particle packing, which generates a larger force-transmission network. Under this scenario, the behavior of the FG sample would not necessarily be attributable solely to reduced interparticle contact area. Although particles with more irregular geometries are generally expected to exhibit inferior flow properties due to their increased propensity for mechanical interlocking, the possibility that the irregular morphology of FG granules diminishes interparticle consolidation cannot be ruled out. These phenomena are therefore likely to arise from a complex combination of both mechanisms.

As demonstrated here, particle imaging data and bulk powder flow measurements provide complementary insights, and integrating both approaches enables deeper interpretation of granulation behavior.

Summary

This application note demonstrates that image-based analysis of particle size, shape, and morphology using the Morphologi 4 is a valuable tool for understanding granulation processes in pharmaceutical formulation science. Morphological characterization provides insight into differences between shear and fluid bed granulation and supports process selection based on particle-level evidence.

Acknowledgement

We gratefully acknowledge the collaboration and significant contributions of Mr. Koji Nakayama, Towa Pharmaceutical Co., Ltd., to this study.