Comparative Study of Microcrystalline Cellulose Grades on Process Robustness in High Shear Granulation

This poster has been presented at the 15th World Meeting on Pharmaceutics, Biopharmaceutics and Pharmaceutical Technology, which took place in Prague, Czech Republic.

Comparative Study of Microcrystalline Cellulose Grades on Process Robustness in High Shear Granulation

INTRODUCTION

Within the Quality by Design (QbD) framework, understanding how critical process parameters (CPPs) affect critical quality attributes (CQAs) is essential for establishing a robust design space (DS). High-shear granulation (HSG) involves multiple CPPs that significantly influence granule size and tablet dissolution behavior, making excipient selection a key factor in improving process robustness. Microcrystalline cellulose (MCC), widely used in HSG for its high water absorption capacity, contributes to the control of granule growth and tablet performance. Therefore, this study investigated the effect of MCC powder property differences on CPP sensitivity by evaluating two representative CQAs — granule size (D50) and 15-min dissolution (Q15) — using a Box–Behnken design as a QbD-based experimental approach to assess process robustness in HSG.

EXPERIMENTS

Table 1. Powder properties and morphology of MCC grades. SEM images were taken at ×200 magnification with a 100 μm scale bar. FIB-SEM images show particle cross-sections.

Table 2. Composition per tablet.

Figure 1. Experimental procedure.

Table 3. Experimental conditions for the Box–Behnken design.

RESULTS

Across the experimental region, lower MCC loading, higher added water content, and longer granulation time tended to increase D50, while higher MCC content, lower water content, and shorter granulation time improved Q15. Compared with PH-101, the UF grades exhibited smaller CPP-induced variation in both D50 and Q15. Among all grades, UF-702, characterized by its larger particle size and higher porosity, showed the most stable performance across formulation and process changes.

CONCLUSION

The impact of MCC grade on the HSG process was evaluated by comparing Ceolus PH-101, UF-711, and UF-702 using a QbD approach.UF grades, characterized by their porous structure and water absorption capacity, showed smaller CPP-induced variation in both D50 and Q15 compared with PH-101. In particular, UF-702, which has a larger particle size, exhibited the most stable granule growth and dissolution profile. These results indicate that employing UF-702 can improve process robustness and may contribute to broadening the DS in HSG processes.

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Source: Tatsuhiro Okuda, Ayumi Yoshida, Tomohisa Fujisawa, Yuji Hayashi, Asahi Kasei, poster: Comparative Study of Microcrystalline Cellulose Grades on Process Robustness in High Shear Granulation