SCALE-UP OF A SPRAY DRY TABLET GRANULATION PROCESS - THERMODYNAMIC CONSIDERATIONS

An aqueous solution of a drug and binder is spray dried and subsequently compressed into tablets. A macroscopic, steady-state application of the Laws of Conservation of Mass and Energy is used to facilitate the scale-up of this continuous granulation process. The resulting equation describes the spray rate (throughput) of the feed solution as a function of: (i) the product of the temperature drop across the spray dryer and the mass flow rate of bone-dry air through the system, (ii) the temperature of the exhaust air, (iii) the absolute humidity of the inlet air, (iv) the overall thermal conductance of the system and (v) the thermophysical properties of the feed solution. This theoretical equation compares favorably to experimental data collected from pilot and production scale processes. Independent variation of the process variables in the model demonstrates that the first parameter is the primary determinant of spray rate. This thermodynamic analysis provides a bridge between processes of different scales. It is considerably more powerful than a series of experiments performed at discrete scales. These results are used in conjunction with equilibrium moisture, tabletting and other experimental data to suggest a rational approach to process scale-up and optimization.