PROCESS SCALE-UP

One of the areas of particle technology that has a special commercial interest is the principle of transferring a particle process from one scale to another, thereby being able to produce particles at different scales with similar properties. Typically, the task goes in the direction of matching first of all the particle size distribution across scale, and secondly, if possible at the same time, to maintain a high-intensity process during scale-up. Other scale-up targets may include: match of morphology and colour as well as mechanical properties of the final product etc.

It is often difficult to find optimum conditions for all parameters at the same time, and scale-up is in practice a trade-off between the target parameters. In the pharmaceutical industry with high-grade products produced in small batches, scale-up will often focus primarily on optimising product properties as the production costs are small compared to the value of the product. This gives little incentive to invest resources into optimising the granulation process intensity. However, in industries with lower grades of bulk granular products produced in several tonnes pr. hour, process intensity may become a highly important scale-up parameter in addition to the before mentioned scale-up targets.

Scaling challenges

Disastrous scaling attempts from the early history of industrial powder technology clearly indicate that scaling of particle processes is far more difficult than the start-up and scaling of processes handling liquids. Modern powder technology scaling involves a variety of issues including typically: problems with production site variances in the particle size distribution, proper coating/binder liquid distribution at different scales, differences in agglomeration tendencies with scale etc.

Still the majority of particle processing equipment sold to the industry is standard units that are only slightly modified according to the specific granular product. Hence, chemical engineers working in the field of powder technology will often find that upscaling in many ways is more of an exercise in finding ways to adapt to the limitations given by the fluid bed chamber design, rather than designing the equipment to work properly with the given process. This is mainly due to the lack of quantitative understanding of the fluid bed coating process both at users and equipment designers, and this shortage becomes even more evident during scale-up. As a consequence of this, direct scale-up of fluid bed processes from lab-scale to production–scale is almost never done without including an intermediate pilot-scale step, where scale-up errors may be detected without losing vast amounts of valuable products.

Seydlitz United Consultants have the scale-up expertise you need

Although industrial needs for scaling down a process do occur from time to time, the typical industrial problem in development or technical transfer projects is far more often to scale up a process. Often product and process properties are optimised in small- and medium-scale pilot fluid beds and then transferred to much larger production-scale. The scale-up of a fluid bed granulation process requires decisions to be made at many levels, including: fixed parameters (e.g. nozzle design and equipment dimensions), parameters related to the raw materials (such as composition, porosity, sphericity and more), coating/binder solution (e.g. viscosity, surface tension, contact angle and more) and the type of equipment, input parameters, operating conditions and processing time etc. With such a variety of interlinked parameters and properties, combined with a lack of quantitative understanding of many of the particle technology processes, it is obvious that scale-up is a challenging task.

Unfortunately, in many cases, the design and variety of the equipment at different scales do not facilitate a straightforward scale-up, and often different important granule properties as well as the general product quality are observed to change with scale. It is often observed that a powder technology process gives the best results the smaller the scale meaning that a lot of time is needed to adjust the production-scale equipment in order to produce products with similar properties. In all, this makes the principles of scaling somewhat more of an art rather than science, and the scale-up of fluid bed processes is in fact still today a mix of physics, mathematics, experience, common sense and qualified guesses. Seydlitz United Consultants offers consultancy in all aspects of scale-up focusing both on process, formulation and end-use product properties.