Bench-Scale Microfluidic Manufacturing of Cross-Linked\nPolyester Microparticles

Polymeric\nmicroparticles used as long-acting drug delivery systems\nprovide advantages relative to conventional oral dosage forms including\nimproved efficacy and safety. However, development of these formulations,\nincluding generics, is constrained by current manufacturing techniques.\nConventional approaches have limited control over process parameters\nand are difficult to scale. Droplet microfluidic techniques produce\nindividual particles sequentially enabling unparalleled consistency\non key material properties including particle size and dispersity.\nWhile microfluidics approaches have much promise, including affording\ncontinuous rather than batch production; designing, constructing,\nand operating these systems is challenging reducing adoption by formulation\nscientists. Herein, we describe the operation of a modular microfluidic\nsystem built with commercially available components to prepare photo-cross-linked\nmicroparticles by droplet generation, inline dilution, and inline\nirradiation with UV. We synthesized monodisperse cross-linked polyester\nmicroparticles with a median size of 37.6 ± 0.4 μm at 20,\n60, and 120 mg batch sizes with average yields of 92 ± 5%. Additionally,\nas a means to tailor material properties, particles were produced\nat varying degrees of cross-linking. The particle’s properties\nwere further characterized, loaded with celecoxib at a low and a high\nlevel, then the <i>in vitro</i> drug release evaluated.\nOverall, the degree of cross-linking and drug loading modulated key\nformulation properties such as <i>in vitro</i> release rate.\nWith this work, we showcase the potential of microfluidic systems\nand aim to foster further adoption of microfluidic techniques to manufacture\ncomparable materials.