Simultaneous Spherical Crystallization and Co-Formulation of Drug(s) and Excipient from Microfluidic Double Emulsions

We demonstrate the fabrication of engineered pharmaceutical formulations of drug(s) and excipient as monodisperse spherical microparticles. Specifically, we fabricate monodisperse microparticles of similar to 200 mu m size containing crystals of a hydrophobic model drug (ROY) embedded within a hydrophilic matrix (sucrose) (DE formulation), which in turn may also contain a hydrophilic model drug (glycine) ((DE)-E-2 formulation). To do this, we dispense the components of the formulation into monodisperse oil-in-water-in-oil (O-1/W/O-2) double emulsions using capillary microfluidics, to subsequently enable simultaneous crystallization and co-formulation via solvent evaporation. We provide detailed morphological and polymorphic characterization of the particles obtained and highlight how (a) microfluidic methods enable formulations that are nearly impossible to achieve using conventional crystallization methods, and (b) these 'bottom-up' methods could potentially circumvent several energy intensive 'top-down' processes in traditional manufacturing, thereby offering the potential of continuous, sustainable pharmaceutical crystallization coupled with advanced formulations.