The Physics of Membrane Emulsification and Applications for Controlled Drug Delivery

In many applications employing particles, the distribution of particle sizes has significant influence over the properties of the resultant material, and this holds especially true for many pharmaceutical products. In the case of depot formulations made of drug-loaded polymer microspheres, particle size significantly impacts the rate and duration of drug release. Thus, if particle size can be controlled, formulation characteristics can be engineered to better meet the needs of the specific situation. Cross-flow membrane emulsification (XME) is a method for manufacturing uniformly sized emulsion droplets which can be used for many applications, including production of drug-loaded polymer microspheres. In XME, a dispersed phase is forced through an orifice in a planar membrane into a simple shear flow set up by a second continuous phase flowing parallel to the membrane surface, thereby generating an emulsion. Though XME has become a popular technique for researchers generating monodisperse emulsions, there has been insufficient characterization of the physics of the XME process. This is true for both simple binary fluid systems, as well as the more complex fluid systems used for the generation of drug-loaded microspheres. In this work, we describe a unique XME system that allows for visualization of the process, providing access to details likely unseen by previous researchers. First employing our system for the study of pure fluids, we successfully show that a simple force balance can be used to model the size of emulsion droplets as a function of process conditions. We also show that the range of applicability of our model corresponds to the region of simple fluid dripping, and that the XME process undergoes a dripping-jetting transition much like the common household faucet. Extending the methods to a more complex case when dissolved polymers, drugs and surfactants are present, we find generally that our earlier results hold true, but only if dynamic interfacial tension is taken into account. Ultimately we show that drug-loaded polymer microspheres of uniform size can be reliably and predictably manufactured across a range of process conditions, and thus we conclude that XME has the potential to produce advanced controlled release formulations