Nanoemulsions: formation, properties and …

1 This journal is The Royal Society of Chemistry 2016 SoftMatterCite this:DOI: : formation, propertiesand applicationsAnkur Gupta,aH. Burak Eral,bcT. Alan Hattonaand Patrick S. Doyle*aNanoemulsions are kinetically stable liquid-in-liquid dispersions with droplet sizes on the order of100 nm. Their small size leads to useful properties such as high surface area per unit volume, robuststability, optically transparent appearance, and tunable rheology. Nanoemulsions are finding applicationin diverse areas such as drug delivery, food, cosmetics, pharmaceuticals, and material , they serve as model systems to understand nanoscale colloidal dispersions.

2 High and lowenergy methods are used to prepare nanoemulsions, including high pressure homogenization,ultrasonication, phase inversion temperature and emulsion inversion point, as well as recently developedapproaches such as bubble bursting method. In this review article, we summarize the major methods toprepare nanoemulsions, theories to predict droplet size, physical conditions and chemical additiveswhich affect droplet stability, and recent IntroductionNanoemulsions are emulsions with droplet size on the order of100 nm. A typical nanoemulsion contains oil, water and anemulsifier.

3 The addition of an emulsifier is critical for thecreation of small sized droplets as it decreases the , the surface energy per unit area, between the oiland water phases of the emulsion. The emulsifier also plays arole in stabilizing nanoemulsions through repulsive electro-static interactions and steric emulsifier used isgenerally a surfactant, but proteins and lipids have also beeneffective in the preparation of 12 Over the pastdecade or more, the research focus has been on preparing nano-emulsions through various methods, broadly classified into twoprimary categories.

4 High-energy and low-energy 15 High energy methods such as high pressure homogenization(HPH) and ultrasonication15consume significant energy(B108 1010 Wkg 1) to make small droplets. On the otherhand, low energy methods exploit specific system propertiesaMassachusetts Institute of Technology, Cambridge, MA, : Fax:+1 617 324 0066; Tel:+1 617 253 4534bDelft University of Technology, The NetherlandscUtrecht University, The NetherlandsAnkur GuptaAnkur Gupta is a PhD candidateat Massachusetts Institute ofTechnology in the Chemical Engi-neering department working withProf.

5 Patrick S. Doyle and Alan Hatton. He is currentlyworking on nanoemulsions andtheir applications. His researchinterests are interfacial science,multiphase fluid flow Burak EralH. Burak Eral is an AssistantProfessor in the Process &Energy Department within the3ME faculty at Delft Universityof Technology since October2015. He also holds a guestfaculty appointment in Van tHoff laboratories in University ofUtrecht. He worked at theMassachusetts Institute of Tech-nology as a postdoc fellow withPatrick S. Doyle after completinghis PhD in Physics of ComplexFluids group in University ofTwente in 2012.

6 His research spans interdisciplinary fieldsincluding: soft matter, process intensification, crystallization,hydrodynamics, rheology and wetting 7th December 2015,Accepted 19th February 2016 DOI: MatterREVIEWP ublished on 23 February 2016. Downloaded on 29/02/2016 13:27:57. View Article OnlineView JournalSoftMatterThis journal is The Royal Society of Chemistry 2016to make small droplets without consuming significant energy(B103 Wkg 1). Phase inversion temperature (PIT)16andemulsion inversion point (EIP)17 19are two examples of lowenergy approaches for the formation of , a few novel technologies such as bubble burstingat oil/water interface20and evaporative ripening21have alsobeen developed for making nanoemulsions.

7 The second section ofthis article reviews the variousmethods to make also discuss the ways to control and predict droplet size basedon system properties and process are kinetically stable, , given sufficienttime, a nanoemulsion phase ,23In Section 3,we discuss the underlying physics behind destabilizationmechanisms such as flocculation, coalescence, Ostwald ripeningand creaming. We show that Ostwald ripening is the dominantdestabilization mechanism for nanoemulsions. We also reviewthe literature on the effect of parameters like nanoemulsioncomposition and temperature on destabilization rates of ,16,18,24 29A short discussion on the trapped speciesmethod for making stable nanoemulsions is also range of nanoemulsion applications spans diverse fieldsincluding drug delivery,30 62where O/W nanoemulsions havebeen used to deliver hydrophobic drugs; the food industry,where flavored nanoemulsions with improved curcumin/b-carotene and digestibility have been prepared.

8 5 7,9 12,63 73andin cosmetic industry where nanoemulsions have been tested forskin hydration and ease of ,74,75 Researchers havealso showed that many problems faced in current methods ofpharmaceutical crystallization processes can be avoided ,77 Nanoemulsions have also been used asbuilding blocks for complex material synthesis such as com-partmentalized nanoparticles and encapsidated oil ,78 81 The fourth section of this paper discusses important propertieson nanoemulsions and discusses a wide range of is some confusion in the literature regarding a precisedefinition of nanoemulsions which are often confused withthe thermodynamically stable microemulsions which ,23 The major differences between classicalemulsions (or macroemulsions), nanoemulsions and micro-emulsions is in droplet size range and stability characteristics,as summarized in Fig.

9 1. Macroemulsions and nanoemulsionsare both thermodynamically unstable, sufficient time,phase separation occurs. However, because of the small size ofnanoemulsions (sometimes also referred as miniemulsions ),nanoemulsions can be kinetically stable over long time metastability has nothing to do with proximityto an equilibrium the other hand, since microemulsionsare thermodynamically stable systems in equilibrium, theyare sensitive to changes in temperature and , nanoemulsions are attractive for aforementionedapplications because they are relatively the least sensitive tophysical and chemical changes.

10 Two recent studies have clarifiedthe distinction between nanoemulsions and microemulsions,and the interested readers are referred to these reports thatdetail the differences between these two classes of liquid-in-liquid ,232 FormationAn understanding of the physics of nanoemulsion formationis critical for the control of nanoemulsion droplet are typically prepared in a two-step processwhere a macroemulsion is first prepared, and is thenconverted to a nanoemulsion in a second step. In this section,we describe various methods developed over the past decadeor so to prepare nanoemulsions, and indicate the progressmade on the prediction andcontrol of nanoemulsiondroplet Alan HattonT.