ADVANCED PHARMACEUTICAL PARTICLE ENGINEERING USING MICROFLUIDIC EMULSION CRYSTALLISATION

Abstract

This thesis presents microfluidic emulsion crystallisation as a versatile technique for single-step pharmaceutical microparticle production. In two different drug-excipient systems, we showcase the versatility of emulsion-based processing for formulating particles with tunable structures. An interplay of phase separation, drug crystallisation and polymer vitrification in drug-polymer droplets during evaporative crystallisation leads to a plethora of microparticle structures. Co-formulation of drug-colloidal silica within water-in-oil droplets yields tunable crystal sizes at the nanoscale. Additionally, two novel spherical crystallisation methods have been established for particle formulation from miscible or partially miscible solvents. Simultaneous antisolvent crystallisation of hydrophilic or hydrophobic drug and gelation of sodium alginate within droplets enables uniform drug-alginate microparticle production. Microfluidic solvent extraction is developed for processing drug-loaded ethyl acetate-in-water droplets, enabling production of spherical microparticles at a grams-per-day-per channel throughput. These new formulations and processes provide valuable insights into drug(-composite) microparticle design and manufacturing, and challenge the conventions of secondary pharmaceutical manufacturing.