In this blog, I discuss ramping up a spray-drying process from bench-top research to industrial-scale production. It’s not a simple matter of increasing the size of the equipment but also process parameters, as increases are not always linear.

I have been speaking with Bruno, a specialist in freeze-drying and spray-drying, about various applications. Spray drying is finding more and more applications, some of which I have spoken about before in my blog, such as its use in advanced battery technology or for drug delivery by inhalable particles . The process is also used for biotech products like yeast and cell cultures, dry powders of agglomerated nanoparticles, microencapsulation and masking of fragrances and aromas, natural products, and Chinese medicine. One of Bruno’s jobs is to perform feasibility studies for clients who need to know whether spray drying will be effective and produce the required results before investing in equipment or large production runs. Performing feasibility studies requires a wealth of knowledge about the process and how various products will react in order to optimize the process and achieve usable results.

I previously wrote about how to perfect the freeze-drying process and the critical factors that affect the drying of biopharmaceutical formulations, such as proteins and peptides . These blogs give a good summary of the most important considerations when planning and performing a spray-drying run. In today’s blog, I would like to focus on another essential consideration for many companies that have either had a feasibility study performed or have done their own research and found a viable process: the next step often involves ramping up production from laboratory to industrial scale – a critical step in bringing a product from research and development to commercialization.

As I mentioned in my previous blogs, perfecting the spray-drying process involves the optimization of several steps, including feed properties (concentration, viscosity, particle size, thermal stability), atomization, airflow (speed, pressure, rate, and temperature), drying chamber (size, material, and shape), quality control (particle size distribution, moisture content, morphology: sample related analytics)), and cleaning and maintenance (I wrote about this before including tips to ensure the longevity and effectiveness of your equipment). Sadly, scaling up a process is not a simple matter of copy-and-pasting the settings you used in your laboratory scale spray drying procedure. A feasibility study will tell you whether a process is feasible, but it will not give you the settings and exact procedures required to perform the process on an industrial scale. It is generally necessary to conduct pilot-scale runs to identify any potential scaling issues. To save costs and reduce the number of pilot trials required, some equations and considerations can improve the likelihood that a scaled-up process will perform as expected.

“Perfecting the spray-drying process involves the optimization of several steps, including feed properties, atomization, airflow, drying chamber, quality control, and cleaning and maintenance.”

The objective is to maintain the most important process conditions during scale-up to obtain the same particle sizes and residual humidity in the produced powders. It is important to clearly define your objectives for scaling up by determining the desired production capacity, product specifications, and any regulatory requirements. The aims of your objectives will influence equipment selection that needs to match the determined capacity and performance requirements. Next comes one of the most important considerations, which are the scale-up factors, such as drying rates, residence time, and heat and mass transfer characteristics, which may vary depending on the equipment used. In a spray dryer, the key process parameters, in order of importance, are the outlet air temperature, the droplet size, and the outlet vapor concentration.

In a spray dryer, the key process parameters, in order of importance, are the outlet air temperature, the droplet size, and the outlet vapor concentration.

Here is a breakdown of the various process parameters and how they may need to be adjusted to ensure a successful transition to larger production runs.

The Feed Rate
Lower feed rates are used for benchtop processes, and the feed rate will need to be increased proportionally to maintain the same drying conditions. The increase is not always linear, and adjustments will have to be made based on the results of pilot trials.

Inlet Air Temperature
Larger runs may require higher temperatures to achieve the same drying rate.

Outlet Air Temperature
The outlet temperature needs to be kept the same, which requires careful monitoring and control, especially since the larger volume of a product can result in a larger heat sink. Care must be taken not to damage heat-sensitive materials.

Spray-Gas / Dispersion-Gas
To achieve the same droplet size, the Spray-Gas rate will have to be adjusted for larger runs to ensure proper atomization, the relationship may not be linear.

Drying-Gas (Aspirator)
The drying gas keeps the particle flow from the nozzle to the cyclone. For larger runs, the rate will have to be increased to ensure the same or similar drying time within the system. Also, this parameter might not be linear.

Pilot trials are critical when scaling up, but there are also some empirical tests that can be conducted to help get things right. One calculation that can help is the water evaporation rate, which can be calculated from a simple mass balance with the following parameters: feed flow rate, the total solids content in the feed, and the residual water content in powder. The feed flow rate can be accurately determined by weighing the feed container before and after an experimental run.

• EVR = Evaporation rate [kg/h]
• FR = Feed flow rate [kg/h]
• TS = Total solids in the feed [kg solids/kg feed]
• RW = Residual water in the powder [kg water/kg wet powder]

The drying air flow rate is controlled by the aspirator setting using benchtop equipment ; however, this is not sufficiently accurate for scale-up calculations as the flow rate changes with the pressure drop across the plant (e.g., due to powder build-up in the filter). Instead, the accurate inlet and outlet air temperature readings should be used as a guide.

The geometric similarity of the instruments is also of importance as it ensures the dimensions of the spray dryer at the larger scale have the same proportions as the smaller scale.

Dimension at Larger Scale/Dimension at smaller scale = Scale Factor

Another important equation used to predict flow patterns in different flow situations is the Reynolds Number (Re). In spray drying, it helps to ensure similar flow conditions at both scales.

• ρ is the density of the fluid (SI units: kg/m3)
• u is the flow speed (m/s)
• L is a characteristic length (m)
• μ is the dynamic viscosity of the fluid (Pa·s or N·s/m2 or kg/(m·s))
• ν is the kinematic viscosity of the fluid (m2/s).

There are a few other considerations that need to be made when scaling up that aren’t directly related to the spray drying parameters, such as safety and compliance, material handling, energy efficiency, quality control, and training. The larger equipment used may require different safety regulations, and handling larger quantities of raw materials, intermediaries, and finished products may require rethinking logistics, including storage and transportation procedures. Sampling and testing may be required to ensure quality control, and staff may require additional training to work with the new equipment and procedures. Collaboration with equipment manufacturers can be a great way to ensure a successful transition to commercial production, as experts like Bruno have a wealth of knowledge and experience in a range of industries. By following the advice here, you should have no trouble scaling up your spray drying process and taking your product to the next commercialization stage.
Till next time,