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

Abstract

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.

Highlights

High-throughput API–excipient co-processing via microfluidic step-emulsification generated uniform microparticles with high flowability, efficient API encapsulation, and tunable solid-state properties.
Bottom-up co-processing enabled superior tablet tensile strength at high drug loadings up to 89 wt% and tuneable tablet dissolution profiles at different excipient loadings.
Multi-faceted characterization revealed a core–shell structure that rationalizes the enhanced tabletability and tunable dissolution behaviour of co-processed microparticles.

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.

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Materials

Naproxen (NPX, Lot Number B23U07085, Purity 98.5%–101.5%) was purchased from BOC Sciences. Artemether (ART, Batch Number AM4NX24K02, Purity 97.0%–102.0%) and Indomethacin (IDM, Batch Number 20240904, Purity 98.5%–100.5%) were purchased from Chemigran Pte Ltd. Felodipine (FLP) was purchased from TCI. Ethyl Cellulose (EC, viscosity 10 cP, 5% in toluene/ethanol 80:20(lit.), extent of labelling: 48% ethoxyl, CAS: 9004-57-3), Cellulose (microcrystalline, powder, CAS: 9004-34-6), α-Lactose.

Jinglun Li, Jun Ho Min, Pankaj Doshi, Arif Z. Nelson, Patrick S. Doyle, Saif A. Khan, From particle engineering to direct compression: Tailoring compaction properties through microfluidic API–excipient co-processing, International Journal of Pharmaceutics, 2026, 127600, ISSN 0378-5173, https://doi.org/10.1016/j.ijpharm.2026.127600.