Emulsions are widely produced for a variety of industrial and pharmaceutical products, and are often defined as a combination of two immiscible liquids, whereby one liquid (the dispersed phase) is in the form of microscopic droplets dispersed in the other liquid (the continuous phase). This is most often oil particles dispersed in an aqueous phase, termed an oil-in-water emulsion, though water-in-oil emulsions are also common.
The majority of emulsions are thermodynamically unstable, and tend to break down over time via creaming, flocculation, Ostwald ripening, phase inversion and coalescence [Figure 1].
Figure 1: The different processes involved in the breakdown of an unstable emulsion.
In cases of food or pharmaceutical products, it is important to minimise these processes, and maintain stability to facilitate the longest possible shelf life.
The droplet size in the dispersed phase can affect the stability of the emulsion. Generally, the smaller the droplet size; the more stable the emulsion. More energy input is required to achieve smaller droplets, and so high pressure homogenisation is often utilised to meet this, due to the high shear it can generate, to reduce droplet sizes to less than 1 µm .
The Avestin range of high pressure homogenisers allows adjustable pressures of up to 30,000psi to be induced upon a sample, as it is forced through a narrow nozzle orifice within the unique, dynamic homogenising valve. As it exits the orifice, shear, cavitation and turbulence disrupts the particles; reducing their size.
It is important to note that higher energy input is not the only factor that determines final droplet sizes. Performing multiple passes through the homogenising valve can have benefits in not only reducing particle sizes further, but in narrowing the overall droplet size distribution (figures 2 and 3, below).
Pharmaceutical drug emulsion (A) before processing. The starting particle size is large (5-10 microns), and the distribution is wide.
Pharmaceutical emulsion (A) after multiple-pass processing at 18,000 psi. Significant droplet size reduction (52 nm) is shown here, with a narrow distribution.
Avestin systems are often utilised to create a “loop”, more so at the pilot and production scale, to allow for efficient multiple-pass processing. This is particularly advantageous in the systems which provide a constant flow-through capacity, independent of the induced homogenising pressure.
The Temperature Effect
Exposure to higher temperatures can impact the stability of an emulsion, since it has the ability to affect the physical properties of oil, water, interfacial films, and surfactant solubility in the oil and water phases .
In addition, as the temperature of emulsions increases; its viscosity decreases. This, in turn, can accelerate the rate of particle collisions, thus making the emulsion less stable. It is therefore important in many cases to control sample temperature during emulsification.
The degree of required control will depend on the sample type, though Avestin have available mechanisms to meet varying degrees of control.
· As a more basic option, a heat-exchanging cooling coil can be installed, to increase the surface area of the product pathway and thus increase heat exchange. This coil can be immersed in a water/ice bath for increased effect.
· For a more stringent control, a sanitary heat exchanger can be installed, which would act as an effective cooling jacket, and often applied where temperatures below 10°C are required. Avestin’s double tube sheet design eliminates the possibility of product contamination, and the accessory is also autoclavable, CIP and SIP sterilisable.
The Avestin Range
The GMP-suitable Avestin range, ranging from the benchtop (3L/hr) scale to the production (1000L/hr) scale, is widely implemented across numerous industries for emulsification, though other applications include cell disruption, particle size reduction (e.g API) and liposome sizing/encapsulation.
At the pilot and production scale, Avestin’s systems utilise a triplex pump design, whereby the pumps work intermittently to facilitate negligible pressure pulsation, and high throughput. This can aid in producing a more stable emulsion, with reduced wear on impact parts within the product pathway.
These large scale units are commonly implemented across the biotech and pharmaceutical industries, due to their robustness, scalability and GMP-suitability, making them an efficient choice at the manufacturing scale.
For more information on the range, and what offers are in place, please contact Biopharma at: firstname.lastname@example.org | 01962 841 092
Figure 1: Lopetinsky, R.G., Masliyah, J. H. and Xu, Z. (2006). Colloidal Particles at Liquid Interfaces, eds. B. P. Binks and T. S. Horozov, Cambridge University Press, Cambridge.
Figures 2 and 3: Avestin, Inc. [image] Available at: http://www.avestin.com/English/efapplications.html#Emulsions [Accessed 8th January 2018].
: Juttulapa, M., Piriyaprasarth, S., Takeushi, H. and Sriamornak, P. (2017). Effect of high-pressure homogenization on stability of emulsions containing zein and pectin. Asian Journal of Pharmaceutical Sciences. 12 (1), 21-27.