Snapshot Analysis: Nano-emulsification Formulation Technology
November 2020 | By Melanie Law, Research Intern at Ascension Sciences
What are Nanoemulsions
Nanoemulsions are isotropic dispersions consisting of 2 immiscible liquids that form droplet sizes ranging from 20 to 200 nm.[1] Nanoemulsions typically exist as an oil phase dispersed in an aqueous phase, commonly denoted as an oil in water emulsion (O/W), or the opposite as a water in oil (W/O) emulsion. A surfactant, which is an amphiphilic molecule with a hydrophobic tail and hydrophilic head group is often added to stabilize such systems. Some formulations require the combination of multiple surfactants to help stabilize the nanoemulsion.[2]
Figure 1: Comparison of common nanoemulsion structure to other nanoparticles
Applications of Nanoemulsions
Nanoemulsions have a variety of applications in research and development, as well as everyday life. In the food industry, nanoemulsions can be used to deliver nutraceuticals, antimicrobials, flavouring agents and more.[3] Such fortifications can help increase the nutritional health benefits as well as shelf-life of food products. Nanoemulsions are also used in the development of novel therapeutics, such as improving the systems for controlled drug release and the delivery of drugs with poor aqueous solubility.
Terminology Review: Nanoemulsions vs Microemulsions
The differences between nanoemulsions and microemulsions are based on how their stability is described. There is a misconception that they differ in size where nano is smaller, but the accepted definitions are based on the fact that microemulsions are thermodynamically stable. Microemulsion stability is imparted often due to a higher surfactant ratio than nanoemulsions. In contrast, nanoemulsions require a more balanced design where droplets are broken up using high amounts of energy (mixing) which are stabilized with surfactants. Therefore, due to the high amount of input energy required to form nanoemulsions, they are thermodynamically unstable in comparison to microemulsions.[4] Under a particular set of conditions, a microemulsion system would remain, whereas a nanoemulsion would eventually break down. Although both can be formed from the same core components: an oil phase, an aqueous phase, and a surfactant, the creation of microemulsions typically require a higher surfactant to oil ratio (SOR) [4], whereas it is possible to form nanoemulsions without the addition of a surfactant [5]. Nanoemulsions formulations also can be made using a wider variety of surfactants.[2]
Emulsification Techniques
Emulsification methods can be high-energy or low energy. In high-energy emulsification methods, external energy is applied to the system in order to create emulsions. Whereas in condensation or low-energy emulsification methods, the energy required comes from the internal energy of the system1. Some common methods to create nanoemulsion are sonication, microfluidization, and phase-inversion temperature method.[4]
Sonication
The creation of nanoemulsions via sonication uses high-frequency sound waves and relies on the phenomenon of cavitation.[6] Cavitation occurs when vapour bubbles form in areas of a liquid that are at lower pressure, due to the liquid being accelerated to high velocities.[7] An example of a device capable of this is a sonicator that releases powerful sound waves. When these cavities collapse it releases shock waves throughout the solution causing the dispersed liquid to break.[6]
This emulsification method can be broken down into 2 steps. First interfacial waves generated by a sonicator and a lack of stability in the system causes phase droplets to erupt into the continuous phase. The continuous phase is the medium in which droplets are suspended in. For instance, in an O/W emulsion, the continuous phase would be water and the phase droplet or dispersed phase would be the oil. In the second step, these droplets are broken down into even smaller droplets due to cavitation.[6]
Low Energy Microfluidics
In this approach the aqueous phase and organic or oil phase flow in individual microchannels towards a laminar flow mixing channel with a particular geometry designed for diffusive mixing. The resulting interaction of the organic and aqueous channels results in spontaneous formation or nanoprecipitation of the particles due to the interaction of charges between the phases. Droplet size can be fine tuned by optimizing parameters such as the total flow rate (TFR) and flow rate ratio (FRR) which is the total speed that both streams are travelling at and the ratio of organic phase to aqueous phase respectively. Microfluidic methods tend to be superior to traditional homogenization approaches6 and can make tunable droplet sizes ranging from 10 nm to 1000 μm.[11]
Phase-inversion Temperature Method
In the phase-inversion temperature (PIT) method, the energy required to make nanoemulsions is obtained from the chemical energy that is released when there is a phase transition.[9] In this method, the sample is prepared at its PIT, which is the temperature when the system contains 3 liquid phases: an aqueous phase, an oil phase, and a bicontinuous middle-phase. Nanoemulsions can also be prepared at its hydrophile-lipophile balance (HLB) temperature, which is where the hydrophilic and lipophilic properties of the system are balanced.[9] The temperature of the sample is then rapidly dropped to a temperature at which the system becomes a 2 phase emulsion consisting of fine droplets.[10]
Optimizing size and stability is key to creating effective therapeutic nanoemulsion delivery systems, which is achieved through tailored formulation development. That’s where research and development laboratories such as Ascension Sciences (ASI) seek to establish novel delivery technologies. ASI’s formulation development services are an efficient option for research-driven firms that require the advantages of nanoparticle delivery for their active ingredients. Learn more: ascensionsciences.com/technology
References
- Solè, I. & Solans, C. Nanoemulsions. in Encyclopedia of Colloid and Interface Science (ed. Tadros, T.) 733–747 (Springer, 2013). doi:10.1007/978-3-642-20665-8_27.
- McClements, D. J. Nanoemulsions versus microemulsions: terminology, differences, and similarities. Soft Matter 8, 1719–1729 (2012).
- Aswathanarayan, J. B. & Vittal, R. R. Nanoemulsions and Their Potential Applications in Food Industry. Front. Sustain. Food Syst. 3, (2019).
- Simonazzi, A. et al. Nanotechnology applications in drug controlled release. in Drug Targeting and Stimuli Sensitive Drug Delivery Systems 81–116 (Elsevier, 2018). doi:10.1016/B978-0-12-813689-8.00003-3.
- Seng, K. K. & Loong, W. V. Introductory Chapter: From Microemulsions to Nanoemulsions. Nanoemulsions – Prop. Fabr. Appl. (2019) doi:10.5772/intechopen.87104.
- Mahdi Jafari, S., He, Y. & Bhandari, B. Nano-Emulsion Production by Sonication and Microfluidization—A Comparison. Int. J. Food Prop. 9, 475–485 (2006).
- Cavitation | physics. Encyclopedia Britannica https://www.britannica.com/science/cavitation.
- pni-app-bt-011.pdf.
- Solans, C. & Solé, I. Nano-emulsions: Formation by low-energy methods. Curr. Opin. Colloid Interface Sci. 17, 246–254 (2012).
- Friberg, S. E., Corkery, R. W. & Blute, I. A. Phase Inversion Temperature (PIT) Emulsification Process. J. Chem. Eng. Data 56, 4282–4290 (2011).
About Ascension Sciences
Employing nanoparticle formulation technology from the cutting edge of genetic medicine, Ascension Sciences Inc. (ASI) is developing cannabinoid nano delivery platforms and techniques for the pharma and nutraceutical industries. ASI’s R&D and formulation development services are an efficient option for research driven firms that require the advantages of nanoparticle delivery for their active ingredients.
For more information, please visit www.ascensionsciences.com.
