EXPERT REVIEW Nano-emulsions and Micro-emulsions: Clarifications of the Critical Differences Nicolas Anton & Thierry F. Vandamme Received: 29 July 2010 / Accepted: 20 October 2010 / Published online: 6 November 2010 # Springer Science+Business Media, LLC 2010 ABSTRACT 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. KEY WORDS emulsion . micro-emulsion . nano-emulsion . SEDDS . self-emulsifying drug delivery system SCIENTIFIC CONTEXT Over the last decades, much research has been done on self-emulsifying systems generating nano-droplets. The applications are wide and generally oriented towards an increase in the bioavailability of drugs, solubilized—due to their submicronic size and great (kinetical or thermody- namical) stability of the suspensions—into the oil droplet core. The many advantages of these systems lie in the self- emulsifying features of the processes themselves, which not only stem from their simplicity (as we will see below), but also from the very low energetic yields involved, thus showing great potential for use in industrial scaling-up ( 1, 2). Research has also been done on the surface functionalization of such nanoparticulate systems with different objectives (5,14,15,22), such as (a) increasing their stealth properties by grafting specific hydrophilic polymers onto the nanoparticle surfaces (i.e. inducing their persistence in the blood pool) or (b) tailoring their surface properties to receptors of specific sites or to a specific environment in order to perform, respectively, active or passive targeting. To this aim, the study of these nano- particulate systems, so-called templates, and their generat- ing processes, appears of fundamental importance since it should precede research on applications such as thera- peutics and diagnosis. Such research on applications requires an understanding of the mechanisms of nano- droplet generation and their structural stability and thermodynamic behaviors. In the literature, these latter points appear somewhat confused. There is often a mix-up between thermodynamically stable systems called micro-emulsions and N. Anton (*) : T. F. Vandamme University of Strasbourg, Faculté de Pharmacie; CNRS 7199, Laboratoire de Conception et Application de Molécules Bioactives, équipe de Pharmacie Biogalénique 74 route du Rhin, BP 60024, F-67401 Illkirch Cedex, France e-mail: nanton@unistra.fr T. F. Vandamme e-mail: vandamme@unistra.fr Pharm Res (2011) 28:978–985 DOI 10.1007/s11095-010-0309-1