Developing HME-Based Drug Products Using Emerging Science: a Fast-Track Roadmap from Concept to Clinical Batch

Area of Science:

• Pharmaceutical Sciences
• Chemical Engineering
• Materials Science

Background:

• Developing enabling formulations like amorphous solid dispersions is crucial for improving drug bioavailability.
• Hot-melt extrusion (HME) is a promising manufacturing technology for these formulations.
• Traditional development workflows can be lengthy and resource-intensive.

Purpose of the Study:

• To present a rational, integrated workflow for developing enabling formulations via hot-melt extrusion.
• To reduce the time and risk associated with product and process development.
• To enable rapid scale-up and technology transfer to Good Manufacturing Practice (GMP) sites.

Main Methods:

• An integrated product and process development framework combining theoretical concepts, modeling, and experimental characterization.
• Rational, model-based design of lab-scale extruder setups, considering thermal load, mixing, and degradation.
• In silico process transfer using a validated computational framework for GMP manufacturing.

Main Results:

• Successful development of enabling formulations in under a year.
• Validation of predicted optimal process setups in pilot plants.
• Demonstrated feasibility of in silico technology transfer to diverse manufacturing extruders.

Conclusions:

• The proposed workflow significantly reduces product and process development risks.
• Accelerates the drug-to-market timeline for enabling formulations.
• Provides a robust and efficient methodology for pharmaceutical manufacturing.