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

Droplet size

Droplet size is controlled through the atomization process as long as suspended particles in the liquid feed are small compared with the droplets created. Atomization is a complex but reproducible process in which droplet size and droplet-size distribution depend mainly on the rheology of the liquid feed, the energy applied, and the liquid-feed rate. The atomization energy can be applied and controlled in various ways such as adjusting the speed of a spinning wheel in a rotary atomizer, the flow of a gas in a two-fluid nozzle, and the liquid-feed pressure in a pressure nozzle (see Figure 3). For a given pressure nozzle and liquid feed, the liquid-feed rate and the liquid-feed pressure are mutually dependent. Either of them can be used in a feedback loop to the feed pump to maintain constant atomization conditions and thereby constant droplet size and droplet-size distribution—as long as the liquid-feed rheology remains constant.

Process-gas flow rate

Spray dryers are generally designed to work correctly within a limited range of drying-gas flow rates: typically 10–20%. The process parameters that have been selected as critical above, however (i.e., inlet's drying-gas temperature, outlet's drying-gas temperature, and feed rate), are sufficient to calculate the heat and balance across the system. The drying-gas flow rate is thus a dependent process parameter, not a variable process parameter.

Though the drying-gas flow rate is a dependent process parameter, it is impractical to control it according to real-time mass-balance and heat calculations. A simple feedback loop between a gas-flow measurement and the main process gas fan works just as effectively. Gas-flow measurement in this case does not require an accurate absolute measurement: a reproducible relative measurement also suffices.

Product-quality risk assessment

Assessments of risk are relative. A risk's magnitude is gauged in comparison with other risks, and "high risk" is relative.

Process measurements and control loops. In most spray-drying applications, a strong, reproducible correlation exists between product quality attributes that are influenced by the process parameters and the basic process measurements (e.g., temperature, pressure, and flow). Basic process measurements are reliable. Regular calibration and preventive maintenance reduce the risk of deviations even further. The undetected failure of a process measurement or control loop is not likely. Because the process parameters must satisfy the heat and mass balance, an undetected error in one instrument would cause other process measurements to deviate from the normal values.

Process measurements and control loops are effective and reliable process controls and constitute a low risk.

A few spray-drying applications do not exhibit an adequately reproducible correlation between the product-quality attributes that are influenced by process parameters and the basic process measurements. In those cases, the process measurements and control loops are not effective for controlling the process and constitute a high risk.

Variation in feed characteristics. Dried products' characteristics change with liquid-feed variations. The process impact of long-term variations in feed characteristics can be difficult to evaluate because the varations are complex and frequently multivariate. One problem is that a limited number of raw-material batches are used in product development, and some sources of variability are easily missed or deemed insignificant.

The combination of control loops that rely on constant response to constant conditions and the difficulty in detecting and analyzing variations in the liquid feed make liquid-feed variations a moderate risk.

In cases with simple liquid feeds (e.g., a solution of one simple chemical compound), the liquid-feed variations become a low risk.

Mechanical errors. Mechanical failures and assembly errors (e.g., missing or damaged gaskets) may cause contamination, deposits, or malfunctions that are not readily detectable. Operator training, standard operating procedures, and preventive maintenance reduce the risk of error, but a high risk of mechanical errors remains.


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