Nano-emulsions and micro-emulsions: clarifications of the critical differences

Much research has been done over the past years on self-emulsifying drug delivery systems, their main interest being the simplicity of the formulation processes, the great stability of the systems and their high potential in pharmaceutical applications and industrial scaling-up. Self-emulsifying drug delivery systems are generally described in the literature indiscriminately as either nano-emulsions or micro-emulsions. Although this misconception appears to be common, these two systems are fundamentally different, based on very different physical and physicochemical concepts. Their differences result in very different stability behaviors, which can have significant consequences regarding their applications and administration as nanomedicines. This paper aims at clarifying the problem, first by reviewing all the physical and physicochemical fundamentals regarding these two systems, using a quantitative thermodynamic approach for micro-emulsions. Following these clarifications, we show how the confusion between nano-emulsions and micro-emulsions appears in the literature and how most of the micro-emulsion systems referred to are actually nano-emulsion systems. Finally, we illustrate how to clear up this misconception using simple experiments. Since this confusion is well established in the literature, such clarifications seem necessary in order to improve the understanding of research in this important field.