Spray drying agglomeration/granulation processes aim to produce particles with a big surface/mass ratio, i.e. small particles. The reconstitution in water of a powder consisting of small particles is, however, difficult and requires intensive mixing in order to disperse the powder before it is totally dissolved. Bigger particles exhibit a better dispersion, but the solubility is negatively affected during the drying operation. Agglomeration obtains both a good dispersion and a complete solution.
A mixer/granulator that dries granules in the same equipment without discharging is commonly called a single pot. The granulation is done in a normal high shear processor; however, care must be taken to avoid the formation of lumps as they cannot be broken down before drying.
Drying options for single-pot systems: the traditional heat source comes from the dryer walls, which are heated; the boiling temperature and vacuum are used to reduce and remove vapours. The heat transfer is related to the surface area of the dryer walls and the volume of product treated. Therefore, this direct heating method is only effective for small scale use.
The introduction of stripping gas into the pot allows large scale operation – a small quantity of gas is introduced in the bottom of the equipment, which passes through the product bed, improving the heat flow from the wall into the product. The gas also improves the efficiency of vapour removal.
Microwave energy can be used to overcome these limitations – providing a further source of energy and has the additional advantage, with organic solvents, that only pure organic vapours must be treated on the exhaust side, and not a mixture of solvent and large volumes of process gas, as would be required in most other wet granulation technologies.
Fluid bed top spray granulation
Fluid beds fitted with spray nozzles can perform granulation and, during the last 10 years, fluid beds have improved dramatically in response to single pot technology competition. It is possible to have completely closed material handling by a closed linking with upstream and downstream equipment. Fully automatic cleaning (clean-in-place CIP and wash-in-place WIP) in fluid beds, using stainless steel filters, now compare favourably with what is possible in a single pot.
High shear granulation/fluid bed drying combination
This system allows full integration with upstream and downstream equipment, and even includes a wet mill between the granulator and dryer. With modern control systems it is easy to load, mix and granulate a second batch in the high shear granulator whilst drying the previous batch in the fluid bed prior to discharge. All equipment can be CIP in a single, automatic process. Whereas a single shaker might be acceptable for drying applications, a twin shaker or blowback filter design should be used for granulation processes.
Continuous fluid bed granulation
The equipment is filled with raw material (similar to a batch unit). After the material has been granulated, the process is switched to the continuous mode, allowing material to be introduced via the rotary inlet valve and discharged as granules by a second outlet valve. The process can be controlled by monitoring the pressure drop over the product bed. The inlet air is segmented, which allows the product in different areas to be treated with different temperatures. Although the process is essentially plug flow, a significant amount of back mixing occurs during processing.
Fluidized Spray Drying (FSD™)
Fluidized Spray Drying produces granules from a liquid in a one-step process. One option is to produce the active in the primary production as granules, so that it only requires blending with excipients suitable for direct compression for secondary processing. This can only be done with actives that are tacky (in a wet state), otherwise the additio n o f a binder
is necessary. Another use of the FSD™ technology is to mix all the ingredients into a solution or suspension and to produce granules in a one-step operation.
The liquid feed is atomized at the top of the tower in a co-current mode during the FSD™ process. After the liquid is evaporated, the particles generated leave the drying chamber together with the exhaust air. These particles are then separated in a cyclone or filter and reintroduced into the drying chamber where they come into contact with wet droplets and form agglomerates. After these agglomerates have reached a certain weight they cannot leave via the top of the tower with the exhaust air, but fall down into the integrated fluid bed at the bottom of the drying chamber. Here they are dried and cooled before being discharged.
Heat sensitive materials
To successfully treat heat sensitive materials, the temperatures and exposure time must be carefully controlled, as should the presence of moisture and oxygen. Single-pot technology provides safe drying under vacuum, particularly if the granulation is done with organic solvents – because the corresponding temperature is even lower. In a spray dryer, however, relatively high temperatures are involved, but only for a very short time. A batch fluid bed granulator can operate at higher air inlet temperatures while spraying and during the beginning of drying, reducing the inlet temperature afterwards to maintain a low product temperature.
The nature of the product dictates which is the more appropriate treatment.