A Material-Process-Equipment Integrated Design Method for Accelerating the Process Development of Twin-Screw Wet...

Area of Science:

• Pharmaceutical Technology
• Chemical Engineering
• Continuous Manufacturing

Background:

• Twin-screw wet granulation (TSWG) offers operational flexibility and consistent quality in continuous manufacturing.
• TSWG process development requires integrating material properties, screw design, and process parameters.
• Botanical drug products present unique challenges for granulation process development.

Purpose of the Study:

• To accelerate twin-screw wet granulation (TSWG) process development using a material-process-equipment integrated design (MPEID) methodology.
• To apply the MPEID methodology to the TSWG process of Guizhi Fuling capsules, a botanical drug.
• To optimize critical screw parameters (CSPs) and critical process parameters (CPPs) for enhanced granule quality.

Main Methods:

• An equivalent formulation was designed to reduce trial costs.
• 3D printing was utilized to create customized screw elements, varying stagger angle (SA) and thickness (thick).
• A two-step design of experiment (DOE) identified critical screw parameters (CSPs) and critical process parameters (CPPs).

Main Results:

• Stagger angle (SA) and thickness (thick) were identified as critical screw parameters (CSPs).
• The liquid-to-solid ratio was identified as the critical process parameter (CPP).
• Optimal TSWG conditions resulted in low torque operation and granules with superior flowability and consistent particle size distribution, comparable to commercial products.

Conclusions:

• The material-process-equipment integrated design (MPEID) methodology is feasible for TSWG process development.
• This approach enables efficient and cost-effective development of TSWG processes for botanical drugs.
• The optimized process yielded Guizhi Fuling capsules with dissolution profiles similar to commercial products.