Multiple Emulsions: Scaling up and Scaling Down for Formulation Design

Multiple emulsions (i.e. droplets within droplets) are attractive encapsulation and delivery vehicles due to their ability to co-encapsulate compounds with widely varying solubility within their multi-phase structure. As such, they have been explored for a range of formulated fluid technologies including consumer products, foods, cosmetics, pharmaceuticals and nanobiotechnology. Recent advances in microfluidic methods to produce multiple emulsions with exquisite control have opened up a wide new design space of complex multi-phase droplets, and various colloidal particles from them. However, these capabilities have yet to meet the demands of technological translation due to problems with scalability in two important respects. First, the devices used have yet to demonstrate production throughput at levels necessary for industrial implementation. Second, the size of droplets is set by the device geometry, which has limited production to droplets that are tens or hundreds of microns in size too large to achieve colloidal stability in many conventional formulations. Here, we review several recently developed methods to produce multiple nanoemulsions (i.e. nanodroplets within nanodroplets) that overcome these limitations in scalability. By combining conventional, scalable emulsification equipment with careful control of mechanical and thermodynamic instability within droplets and at their surface, these methods are able to produce large quantities of colloidally stable multiple emulsions with well-specified morphologies. These complex droplet morphologies are retained upon the addition of various material pre-cursors, and the droplets are stable over the time scales required for material chemistry, thereby enabling their use as templates for complex nanoparticles. As a detailed demonstration, we show how oil-in-water-in-oil double nanoemulsions can be used to template the synthesis of oil-filled nanogels for encapsulation and controlled delivery of poorly water-soluble active ingredients.