Producing Monodisperse Drug-Loaded Polymer Microspheres via Cross-Flow Membrane Emulsification: The Effects of Polymers and Surfactants

Cross-now membrane emulsification (XME) is a method for producing highly uniform droplets by forcing a fluid through a small orifice into a transverse flow of a second, immiscible fluid We investigate the feasibility of using XME to produce monodisperse solid microspheres made of a hydrolyzable polymer and a hydrophobic drug, a model system for depot drug delivery applications This entails the emulsification of a drug and polymer-loaded volatile solvent into water followed by evaporation of the solvent We use a unique side-view visualization technique to observe the details of emulsion droplet production, providing direct information regarding droplet size, dripping frequency, wetting of the membrane surface by the two phases, neck thinning during droplet break off, and droplet deformation before and after break off To probe the effects that dissolved polymers, sin factants, and dynamic interfacial tension may have on droplet production, we compare our results to a polymer and surfactant-free fluid system with closely matched physical properties Comparing the two systems, we find little difference in the variation of particle size as a function of continuous phase flow rate In contrast, at low dripping frequencies, dynamic interfacial tension causes the particle size to vary significantly with drip frequency, which is not seen in simple fluids No effects due to shear thinning or fluid elasticity arc detected Overall, we find no significant impediments to the application or XME to forming highly uniform drug-loaded microspheres.