High-throughput eutectic screening and hot-melt extrusion enable rapid development of nifedipine amorphous solid...

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Chemical Engineering

Background:

• Developing eutectic-based amorphous solid dispersions (ASDs) is challenging due to the extensive time and material needed for drug-coformer screening.
• Identifying suitable drug-coformer combinations is a critical bottleneck in ASD formulation.

Purpose of the Study:

• To present a miniaturized, high-throughput workflow for accelerated eutectic formulation design.
• To integrate picolitre-volume inkjet printing, predictive thermodynamic modeling, and scalable processing for efficient ASD development.
• To shorten formulation timelines for poorly soluble active pharmaceutical ingredients (APIs).

Main Methods:

• Utilized picolitre-volume 2D inkjet printing to create microarrays of binary systems.
• Employed predictive thermodynamic modeling, specifically the Schroeder-Van Laar equation, to forecast eutectic compositions and temperatures.
• Validated predictions through scale-up, full phase-diagram construction, and hot-melt extrusion for ASD generation.

Main Results:

• Successfully identified promising eutectic pairs rapidly using minimal material through microarray screening.
• Thermodynamic modeling predictions were validated experimentally.
• Demonstrated the feasibility of generating amorphous solid dispersions from selected eutectic formulations.

Conclusions:

• The developed end-to-end strategy offers a robust and material-efficient platform for eutectic-based ASD development.
• This integrated approach significantly reduces formulation timelines for poorly soluble APIs like nifedipine.
• The workflow combines ultrafast screening with continuous manufacturing principles for streamlined drug development.