From particle engineering to direct compression: Tailoring compaction properties through microfluidic API-excipient co-processing

Direct compression (DC) is an attractive route for tablet manufacturing, yet its impact remains constrained by the poor flowability of many active pharmaceutical ingredients (APIs) and the high excipient loading required for reliable compaction. Here, we introduce a microfluidic particle engineering approach that co-processes API with polymeric excipients to produce highly flowable microparticles with tuneable compaction behaviour. Notably, excellent tabletability is achieved with minimal excipient loading, thereby addressing both critical requirements of DC. Using a parallelized step-emulsification device, monodispersed droplets containing dissolved naproxen (NPX) and ethyl cellulose (EC) were fabricated and subjected to antisolvent extraction to produce spherical co-processed microparticles. Robust tablet tensile strength exceeding 5 MPa was achieved with only 11% excipient loading - enabled by a self-assembled core-shell structure featuring an EC-rich shell encapsulating an NPX-rich core. Moreover, adjusting the API-to-excipient ratio produced microparticles with distinct morphologies and solid-state outcomes, resulting in greater tabletability with higher excipient loading. Overall, the microfluidic platform approach allows for a systematic study of self-assembled particle structures produced by API-excipient co-processing and their impact on DC formulations.