A General Route for Nanoemulsion Synthesis Using Low-Energy Methods at Constant Temperature.

The central dogma of nanoemulsion formation using low-energy methods at constant temperature-popularly known as the emulsion inversion point (EIP) method-is that to create O/W nanoemulsions, water should be added to a mixture of an oil and surfactant. Here, we demonstrate that the above order of mixing is not universal and a reverse order of mixing could be superior, depending on the choice of surfactant and liquid phases. We propose a more general methodology to make O/W as well as W/O nanoemulsions by studying the variation of droplet size with the surfactant hydrophilic-lypophilic balance for several model systems. Our analysis shows that surfactant migration from the initial phase to the interface is the critical step for successful nanoemulsion synthesis of both O/W and W/O nanoemulsions. On the basis of our understanding and experimental results, we utilize the reverse order of mixing for two applications: (1) crystallization and formulation of pharmaceutical drugs with faster dissolution rates and (2) synthesis of alginate-based nanogels. The general route provides insights into nanoemulsion formation through low-energy methods and also opens up possibilities that were previously overlooked in the field.