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

Amorphous solid dispersion (ASD) is a widely used formulation strategy for improving the apparent solubility and oral absorption of poorly water-soluble drugs. However, established commercial ASD manufacturing processes often generate powders with broad particle size distributions, irregular morphology and poor powder flowability, all of which complicate downstream processing. In this work, we introduce a droplet-templated ASD manufacturing process that combines step-emulsification co-processing of a polymer and drug with continuous anti-solvent extraction to produce highly monodisperse ASD particles. We produce intermediate ASD drug powder products with favorable particle attributes, including high monodispersity, improved flowability, and compatibility with downstream tableting. In contrast with prior reports on microfluidic production, this process allows the production of sufficient quantities of powder to enable compression into drug products (tablets). The tablets thus produced meet stringent drug product specifications (tensile strength, extended supersaturation dissolution profile and residual solvent below ICH limits). These results demonstrate that droplet microfluidics, traditionally viewed as a small-scale process, can be leveraged as a promising alternative manufacturing platform for ASDs with industrially relevant throughput for high-value pharmaceutical products.