Highlights

• Granulation in Pharma-11effectively replicates CG-1 performance in continuous TSWG.
• Formulation, L/S ratio and screw configuration influence granule properties.
• Distributive mixing elements in screw configuration enhance particle coalescence.
• Milling minimized scale effects, yielding uniform granules and tablet quality.

Abstract

Continuous twin-screw wet granulation (TSWG) is a robust alternative to conventional batch granulation for manufacturing solid oral dosage forms. However, differences in equipment design can result in distinct granulation behaviors, making equipment comparisons important. In this study, we evaluated the practical transferability between two geometrically distinct granulators, Pharma-11 and ConsiGma-1 (CG-1), to determine how equipment characteristics, process parameters, and formulation variables influence granule and tablet attributes. A design of experiments (DoE) approach assessed the effects of formulation composition, liquid-to-solid (L/S) ratio, and screw speed. In the Pharma-11, screw configurations with and without distributive mixing elements (DMEs) were examined and compared with size control element (SCE) configurations used in CG-1. Granule size distribution (GSD) analysis showed that CG-1 produced larger granules (up to ∼2 mm), whereas granules from Pharma-11 were limited to ∼1 mm, reflecting differences in barrel diameter. When granule sizes were normalized to barrel dimensions, dv values were closely aligned between the systems. Calibration further reduced size differences, yielding highly comparable GSD profiles. The inclusion of DMEs in the Pharma-11 configuration decreased the fraction of fines while producing granules with GSD similar to those from the CG-1. The results demonstrate how equipment design, configuration, and operational constraints influence granulation behavior and product attributes. Although Pharma-11 is not typically used as a standard TSWG development platform, it can generate granules comparable to those produced by CG-1 when operated within its limitations. This supports its use as an effective early-stage development tool when material is limited or process optimization is needed.

1. Introduction

In recent years, the application of continuous manufacturing (CM) in the production of pharmaceutical solid dosage forms has gained significant traction among manufacturers. This shift has been supported by the publication of ICH Q13, Continuous Manufacturing of Drug Substances and Drug Products, which highlights the substantial benefits of CM in enhancing product quality, consistency, and flexibility. It also promotes data-driven approaches to ensure product safety while reducing production costs and material waste.

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