Scale up is a critical stage in any production process, and it is increasingly seen as a vital factor in decision-making when specifying a new mixer. There are a number of key factors that must be taken into consideration by manufacturers wanting to scale up and expand their production process. It would be ideal to consider these factors before laboratory scale production is underway so that scale up can progress seamlessly, without the need for reformulation or changing the existing mixing process.

Despite a number of theories, equations and other academic research in the public domain, a common issue amongst manufacturers across the process industries is successfully scaling up products formulated in the lab. As agitators are generally carrying out relatively simple tasks, it is possible to forecast their performance at a larger scale with a high degree of certainty. High Shear mixers such as rotor/stator devices are much tricker to forecast. The versatility of these mixers means that more complex factors are involved, with many mixing operations such as homogenizing, particle size reduction, emulsification, etc. occurring at the same time. 

One of Silverson Machines' unique selling points is the ability to scale up our mixing equipment from the laboratory to full scale production models. With over 80 years' practical experience in scaling up, we offer unrivalled know-how and expertise.

So, what needs to be taken into consideration when scaling up from the laboratory to full-scale production? Matt Smith, Sales Director at Silverson Machines explains which key factors must be thought about:

The type of mixing equipment

As batch sizes increase, a manufacturer must decide whether to use in-tank or In-Line mixing. Over a certain batch size, it becomes more efficient and economical to switch to In-Line mixing, 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 larger batch than an in-tank mixer of similar power. Silverson laboratory mixers can provide a good indication of whether or not a process is viable with a high shear mixer, but we also offer dedicated In-Line laboratory scale models which may be more appropriate when a process is going to be carried out with an In-Line mixer at production scale.

Tank turnover rate

When batch sizes and vessels increase in size, the processing time will do the same. Manufacturers must take into consideration the tank turnover rate - the amount of time it takes to recirculate the product - and be prepared to mix for longer as mixer flow rates will decrease as batches become larger. This may mean that additional equipment, such as feed pumps or scraper/stirrer units in the vessel are needed to maintain flow rates when mixing more viscous products.

Other equipment 

When mixing at pilot scale what is used to assist the process - moving the beaker by hand? Using a spatula to agitate the product in the vessel? When this is necessary at smaller scale, then manufacturers may need to be prepared to invest in additional agitating equipment when scaling up in order to replicate the process. 

Other types of ancillary equipment to be used when scaling up such as vessels, hoses/pipes and pumps is also very important to discuss beforehand. Usually, manufacturers will want to use their existing equipment, which can work but may have its limitations. For example, if a pilot scale processing line was using vessels with 1" outlets and 1" hoses as standard, this set-up would not be able to successfully run any of the production scale powder/liquid mixers from Silverson. So, if the intention is to scale up to a much higher capacity machine this must be flagged beforehand and appropriate fittings must be used. 

Mixing parameters

The usual high shear mixing “parameters” - tip speed, stator design, mixing time - need to match. At Silverson, we emphasize to our customers prior to the beginning of their pilot scale trials that anything extreme among these parameters can become extremely difficult to scale up. As such, these parameters should stay within sensible limits. For example, a laboratory mixer running at 10,000 rpm for over an hour in a 1-litre beaker to get the desired product quality may be impossible to scale up. 

Another issue to remember concerning mixer speed is that lab mixers need to be run at a faster rpm than their production counterparts in order to ensure the peripheral tip speed – and therefore the shear rate – is comparable between laboratory and production scale equipment. It’s a common error to run a lab mixer at 3,000 rpm because this is the speed most production models run at, but this won't give you an accurate idea of full-scale results; in fact a lab mixer running at 8,000 rpm has a tip speed that more closely matches the standard 3,000 rpm of most larger in-tank batch mixers.

The stator design or geometric similarity needs to be taken into consideration when wanting to replicate results. At Silverson, the Verso Laboratory-scale In-Line mixer has the same geometric design as full-scale UHS In-Line mixers, meaning the rotor and stator are engineered to the same fine tolerances. This allows us to easily forecast the results of larger batches at smaller scale. 

Silverson Machines offer the widest capacity range from a single manufacturer, from laboratory scale volumes of 1ml up to production scale mixers capable of mixing volumes of up to 8,000 gallons. Silverson has been a pioneer in the design and manufacture of a new generation of “Ultra Sanitary” mixing equipment specifically aimed at stringent applications and the pharmaceutical industry. This range of Ultra Sanitary mixers is 3A tpv Certified and designed to comply with FDA and cGMP requirements; some models are also EHEDG Certified. 

To discuss your pharmaceutical application please contact: [email protected] or visit www.silverson.com

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