The use of microwaves during high-shear wet granulation and drying in a single-pot processor is shown to be more effective and efficient than gas-stripping.

Single-pot processing is an established pharmaceutical technique for high-shear wet granulation and drying. Although several drying techniques can be used in single-pot processing, the basic principle relies on the application of a vacuum in the bowl, which lowers the evaporation temperature of the granulation liquid. The traditional heat source is the heated dryer walls, and heat transfer is directly related to the surface area of the walls and the volume of the product. To enhance the drying process and reduce drying times, additional drying techniques can be implemented. The efficiency of two of these techniques — microwave drying and gas-stripping — was examined. 

Gas-Stripping enhances vacuum drying by injecting a small amount of gas through the product mass during the drying phase. Microwave Drying relies on additional energy being supplied that’s preferentially absorbed by the solvents in the process to enhance evaporation.

Theoretical Efficiency Comparison

Gas-Stripping Calculations: In a 75 L machine, the gas flow used depends on the equipment manufacturer. According to our data, however, the maximum flow varies between 35 and 100 L/min.5 The calculations were based on the use of dry purified air at room temperature (20 °C). At this temperature, the maximum water content of air is 17.3 g/m3.

Assuming the air is absolutely dry when entering the product (0% RH), and is fully saturated when exiting the machine, a maximum of 0.9169 g/min and 1.73 g/min of water can be removed at airflows 35 L and 100 L per minute, respectively.

It is well known that when air is heated, its moisture holding capacity increases. For example, air at 60 °C can contain a maximum of 130 g/m3 of water. However, supplying heated air to the process would not result in an additional water removal of 4.55 g/min at an airflow of 35 L/min, or 13 g/min at an airflow of 100 L/min. This is because when the air comes into contact with the product, its temperature is adjusted to that of the product. If drying is donecarried out at 40 mbar, for example, the temperature of the product would be 28 °C, meaning that the air will also be 28 °C, and the moisture absorption capacity is thus limited to approx. 30 g/m3 (or 1.05 g/min and 3 g/min, respectively). 

The energy of the heated air, when it cools down to the temperature of the product, provides energy for evaporation, but this does not impact the absorption capacity of the air and is not taken into account for this calculation. The may explain why, in gas-stripping, the air is seldom heated (as well as increased complexity and cost of the installation).

Microwaves Calculations: A 75 L single-pot processor contains a 3 kW magnetron. The actual microwave output is limited to 2.4 kW, which corresponds to an energy supply of 2.4 kJ/second. If the pressure in the bowl is 40 mbar (bowl pressure must be 30–100 mbar when working with microwaves), the latent heat of evaporation of water is 2433 kJ/kg. With a microwave output of 2.4 kW, 144 kJ of energy is delivered to the product every minute, which is sufficient to provide enough energy to evaporate 59.19 g of water.

Experimental Comparison

Experimental data

To confirm the theoretical calculations, a small-scale trial was done carried out using an UltimaPro™ 25 (25 L bowl capacity single-pot processor). Lactose monohydrate (8 kg) was manually loaded into the machine, purified water (1 kg) was sprayed onto the lactose using a pressure vessel at 2 bar and a flat beam spray nozzle (LX2, Delavan), and an impeller speed of 200 rpm was used to obtain a homogenous water/lactose mixture (without creating a granule). After wetting, mixing was continued for 1 minute before the drying phase was starting.

 The results confirmed the theoretical calculations, showing that microwaves have a much higher water removal capacity that than gas-stripping. It was demonstrated that microwaves were capable of removing the water (approx. 1 kg) in 40 minutes, whereas gas-stripping took more than 3 hours to remove the same amount.


Both the theoretical calculations and experimental data showed that vacuum drying is significantly improved when enhanced with microwaves compared with gas-stripping. Although gas-stripping does improve the vacuum drying process, it cannot replace a microwave drying system without prolonging the drying time. In addition, process scale-up must also be considered: drying times will remain the same for both small- and large-scale applications when using microwaves, whereas the drying times will be longer for gas-assisted vacuum drying because of the impact of the volume:surface ratio when transferring from small- to large-scale.


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