A Risk-Based Approach to Product and Process Quality in Spray Drying - Pharmaceutical Technology

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A Risk-Based Approach to Product and Process Quality in Spray Drying
Process designs and control strategies can be improved by adopting a risk-based approach to product quality. The author describes how this approach can be applied to spray-drying operations.


Pharmaceutical Technology


Identifying the important process parameters


Figure 1
In a spray dryer, droplets or particles are dried while they are suspended in the drying gas. During the drying process, heat is transferred from the drying gas surrounding the droplets or particles, and solvent evaporates from the droplet or particle surface into the surrounding drying gas (see Figure 1). The process also involves various complex diffusion processes, most of which are specific to the product–solvent combination used. This complexity makes liquid-feed composition an important part of early process development. Because the liquid-feed composition rarely can be used for process-control purposes, however, the parameters available for process control are drying temperature, drying-gas humidity, and droplet size.

The conditions under which the droplets are transformed into particles influence the final solvent content and the particle morphology.

Drying temperature


Figure 2
In a spray dryer, it is important to distinguish between dryer-inlet temperature, product temperature, drying temperature, and dryer-outlet temperature. In a well-designed cocurrent spray dryer, the intense mixing of spray and drying gas results in fast cooling of the drying gas by the evaporation of solvent. The end result is that the temperature in the drying chamber is practically equal to the spray-dryer outlet temperature. This parity can be measured and calculated with computational fluid-dynamic models (see Figure 2).

Because of the evaporation of solvent from the product, the droplet or product temperature remains lower than the spray-dryer outlet temperature during the entire drying process. The droplet or product temperature also remains lower than the spray-dryer outlet temperature in the high-temperature region at the drying-gas inlet, where the rate of evaporation is at its highest and the droplet temperature is at its lowest (i.e., approaching the wet-bulb temperature). The product temperature at the discharge is typically between 5 and 20 C colder than the drying-gas temperature at the outlet.


Figure 3
The importance of the drying-gas temperature at the spray-dryer outlet is clearly seen in experiments where the correlation between product characteristics and outlet temperature is stronger than most other process variables. The outlet's drying-gas temperature is usually fixed at a product-specific set point by a feedback control loop. The feedback loop normally adjusts the inlet's drying-gas temperature or the liquid-feed rate to maintain the outlet's drying-gas temperature at the set point (see Figure 3).

Drying-gas humidity

The solvent-vapor content in the drying gas is the sum of the solvent-vapor content in the inlet drying gas and the evaporated solvent. In most applications, the evaporated solvent is the major contributor. Because the evaporation rate is proportional to the difference between the inlet and outlet drying-gas temperature, an increase in the inlet drying-gas temperature (at constant outlet drying-gas temperature) results in an increase in drying-gas solvent-vapor content.

The control of the inlet's drying-gas temperature depends on the control strategy applied for the outlet's drying-gas temperature. When the outlet drying-gas feedback loop adjusts the inlet's drying-gas temperature, the fixed set point for the liquid-feed rate indirectly sets the inlet's drying-gas temperature level (see figure 3). Alternatively, a feedback loop maintains the inlet's drying-gas temperature at the set point by adjusting the main process gas heater.

The solvent-vapor content in the inlet drying gas is controlled effectively and accurately by adjusting the condenser's outlet gas temperature (i.e., the dew point of the gas). In applications that use ambient air as the drying gas, the condenser is replaced by a dehumidifier or sometimes completely omitted.


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