Scalable generation of droplet-templated amorphous solid dispersions using continuous antisolvent extraction

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Chemical Engineering

Background:

• Amorphous solid dispersions (ASDs) enhance solubility for poorly water-soluble drugs.
• Conventional ASD manufacturing yields particles with poor flowability and broad size distributions, complicating downstream processing.
• Scalable and efficient ASD production methods are needed.

Purpose of the Study:

• To develop a droplet-templated manufacturing process for producing highly monodisperse ASD particles.
• To evaluate the particle attributes and downstream processability of the manufactured ASDs.
• To demonstrate the potential of microfluidics for scalable ASD production.

Main Methods:

• Utilized step-emulsification and continuous anti-solvent extraction within a droplet-templated microfluidic system.
• Co-processed polymer and drug to form intermediate ASD powder products.
• Compressed ASD powders into tablets and evaluated drug product specifications.

Main Results:

• Achieved highly monodisperse ASD particles with improved flowability and compatibility with tableting.
• Produced ASD tablets meeting stringent specifications for tensile strength, dissolution, and residual solvents.
• Demonstrated industrially relevant throughput for droplet microfluidic ASD manufacturing.

Conclusions:

• The droplet-templated process offers a promising alternative for manufacturing ASDs with superior particle attributes.
• Microfluidics can be scaled for industrial production of high-value pharmaceutical products like ASDs.
• This method addresses limitations of traditional ASD manufacturing, enabling efficient downstream processing and high-quality drug products.