Which techniques are best when the mixing process becomes as complex as the liquid matter involved? Michelle Knott finds out.
When a mixing application involves combining liquids that are all aqueous or all oily, a simple agitator-based system or static mixer is often enough to get the job done. But for emulsification applications, which involve suspending droplets of an oily phase in an aqueous phase or vice versa, users may find that only a more vigorous mixing solution can generate the high-shear forces needed to produce a stable product.
“Conventional agitators can give satisfactory results across the broadest range of capacities on viscosities from that of water to highly viscous slurries in many applications, but their effectiveness tends to be limited to simple duties such as blending liquids of similar viscosities, maintaining in-tank uniformity and promoting heat transfer,” says Matt Smith, sales director with Silverson Machines.
“With more demanding duties such as the formation of an emulsion or suspension, and blending liquids with widely differing viscosities, an agitator is at best only effective as a ‘process aid’, supplementing the action of equipment with a more positive mixing action.”
The challenge is that forming an emulsion is essentially trying to mix the immiscible. Get it wrong and the resulting product will be unstable, with the oil and water phases separating again.
With more demanding duties such as the formation of an emulsion or suspension, and blending liquids with widely differing viscosities, an agitator is at best only effective as a ‘process aid’
Matt Smith, sales director with Silverson Machines
“When forming an emulsion, stability is the most important consideration, which is defined as the ability to resist changes in its physiochemical properties over time. Instability can be caused by mechanisms such as sedimentation, creaming, flocculation, coalescence and phase inversion – mechanisms which the user wants to avoid,” explains Ashley Morgan, sales specialist for high-pressure homogenisers with BioPharma Process Systems.
“These mechanisms can be avoided by having a desirable sample temperature, pH, droplet size, zeta potential, size distribution, ionic strength, and other factors.”
So a wide range of factors can play a role in maintaining the stability of an emulsion, with chemical additives often used to help, for instance.
But as far as the physical mixing process goes, the vital thing is to create a dispersed phase of small, reasonably uniform droplets that are evenly distributed throughout the continuous phase.
Two types of technology most commonly fit the bill – rotor-stator systems and high-pressure homogenisers. Other more unusual techniques such as sonication tend to be confined to specialist, small-scale applications because they’re more difficult to scale up.
When forming an emulsion, stability is the most important consideration
Ashley Morgan, sales specialist at BioPharma Process Systems
High-shear mixers based on rotor-stator technology use a workhead that contains a fast-moving, bladed rotor housed within a perforated stator.
Rotor-stator systems include in-line versions, which position the workhead in the line to create a continuous process, as well as in-tank versions for batch production.
“The advantages of the rotor-stator mixer over conventional agitators stem from the multi-stage mixing/shearing action, as materials are drawn into the workhead by the high-speed rotation of the rotor blades. These are subjected to intense hydraulic and mechanical shear, then forced out through the [perforated] stator at great speed and projected back into the mix,” says Smith.
“The high-shear rotor-stator principle offers unrivalled versatility. A single machine can mix, emulsify, homogenise, solubilise, suspend, deagglomerate and disperse – duties which in the past would have required several different pieces of processing equipment.”
Euromixers is another supplier offering rotor- stator systems for emulsification duties. Application engineer Joel Davies notes that in-line rotor-stator systems effectively double up as centrifugal pumps, moving fluids as the rotor draws them through the workhead.
“It’s a trade-off. Do you want more pumping or more shear?” says Davies. “Our systems generally rotate at a constant 3,000 rpm, so if you’re using them for something that’s quite easy to disperse you can go for larger holes in the stator and get a higher throughput.
“Lower-viscosity fluids are generally easier to disperse, but it also depends on how the two phases interact chemically.”
In contrast, in-tank batch emulsification systems do not provide a fluid transfer function, although flow of product through the workhead is important in order to circulate the material around the vessel.
“Batch systems are not as efficient as in-line systems, because inside the tank volume you’ve got many passes going through the workhead, which may not be necessary to achieve required droplet size,” says Davies.
It’s a trade-off. Do you want more pumping or more shear?
Joel Davies, application engineer, Euromixers
On the other hand, multiple passes through the emulsifying mixer (whether it uses a rotor-stator workhead or it’s a high pressure homogeniser) will provide a tighter globule size distribution than a single pass, which may be worth bearing in mind for some applications.
To optimise efficiency, Silverson advises users to opt for high- shear in-line mixers over batch mixers if the batch vessel is over a certain size. Depending on the viscosity, it suggests a cut-off point around the 400 gallon mark (roughly 1,800 litres).
“While we do offer batch machines for much larger capacities, in general beyond this point an in-line mixer is often the most efficient and economical option.
“This is because the in-line mixer’s energy is concentrated on the small volume within the mixing chamber at any given moment, rather than expended on circulating the entire contents of the vessel, as well as the mixing task itself. Consequently a relatively small in-line mixer can process a large batch,” says Smith.
High-shear in-line or in-tank rotor-stator mixers can generally produce a droplet size in the range between two and five microns, which is suitable for products in industries such as personal care and food; including creams, lotions, ointments, sauces and flavour emulsions.
However, for some products in the biotech and pharmaceutical industries, a globule size in the nanometre range may be required. Typically, high- pressure homogenisers are the preferred option in these applications.
“High-pressure homogenisation forces a sample through a very narrow orifice at high pressures, which allows stress forces such as shear, cavitation and turbulence to rupture particles [or globules]. These particles immediately reform, only smaller and more uniform,” says Morgan.
“The higher the applied pressure, the smaller the particles reform. A narrow size distribution can be achieved by applying the optimal number of passes through the system.”
BioPharma’s Avestin high-pressure homogenisers [the C3 is pictured left] can apply a pressure of anywhere up to 45,000 psi. The pressure is adjustable, enabling the resulting globule size to be closely controlled. And because the entire product flow must pass through the orifice, Morgan argues that it’s easier to guarantee complete emulsification rapidly and efficiently, compared to in-tank rotor-stator batch systems.
The other vital component of such a homogeniser is the valve, he explains: “The main advantage of using an Avestin homogeniser is that it has a dynamic, flexible valve. This is able to freely open and close, which reduces wear rates, and greatly reduces blockage risk.
“Other homogenisers tend to have a static, fixed geometry valve. These can be more susceptible to wear and blockage.”
Rotor-stator specialists recognise that some applications call for a high-pressure homogeniser. Says Smith: “For the few applications that demand submicron particle or globule sizes a high-pressure homogeniser may be required. Where this is the case, passing the product through a [rotor-stator-based] high-shear Silverson mixer homogeniser first will dramatically improve throughput, process efficiency and reduce operating costs.
“A high-pressure homogeniser works better when fed with a premix of uniform and fine globule or particle size, allowing the product to pass through the homogeniser at a much faster rate.”