Downstream processing from melt granulation towards tablets: In-depth analysis of a continuous twin-screw melt...

Area of Science:

• Pharmaceutical Sciences
• Chemical Engineering
• Materials Science

Background:

• Twin-screw melt granulation (TSMG) is increasingly recognized for pharmaceutical formulation.
• Understanding variability in TSMG is crucial for its adoption in solid oral dosage forms.

Purpose of the Study:

• To analyze the continuous TSMG process, identifying critical process parameters (CPP).
• To evaluate the impact of process and formulation on critical quality attributes (CQA) of granules and tablets.
• To screen amorphous polymers as binders for high-dosed melt granules.

Main Methods:

• Screening of amorphous polymers for acetaminophen and hydrochlorothiazide melt granulation.
• Quality-by-Design (QbD) approach for hydrochlorothiazide TSMG, milling, and tableting.
• Analysis of granulation torque, screw speed, throughput, and glass transition temperature (Tg).

Main Results:

• Amorphous polymeric binders yielded high milling efficiency, low fines, high granule yields, and low friability.
• Granulation torque was a critical parameter, increasing with high Tg polymers during extended runs.
• Optimizing screw speed, throughput, or using lower Tg binders mitigated torque issues.

Conclusions:

• TSMG is a viable option for solid oral dosage form development.
• Amorphous polymeric binders enhance granule quality and downstream processability.
• Process parameter optimization ensures robust TSMG for consistent granule and tablet quality.