2025 AIChE Annual Meeting

(440c) Application of Psychrometric Principles to Spray Drying Process Design for Pharmaceutical Products

Authors

Ariel Muliadi, Genentech
Spray drying is commonly used in the pharmaceutical industry as a means to improve the solubility of small-molecule drugs and, more recently, enable oral administration of macromolecules. The bulk properties of spray-dried materials are often a function of the equipment parameters used to produce them, namely, the drying gas rate and temperature, the liquid spray rate, the dryer inlet and outlet temperatures, and, in the case of a ‘closed loop’ dryer, its condenser temperature. The development of a formulation containing such spray-dried materials often necessitates their bulk properties be optimized, especially in cases where the spray-dried materials comprise a significant portion of the formulation.

This study pertains to the use of psychrometry–the thermodynamic quantities of gas-vapor mixtures–to analyze the process characteristics of closed-loop spray dryers. Relevant thermodynamic equations are reviewed. Temperature-dependent activity coefficients are used to approximate the liquid-phase non-ideality when predicting the liquid/liquid and liquid/vapor equilibria in cases where the spray drying solution comprises two different solvents.

We demonstrate that the spray-dried material's bulk density is a linear function of the predicted relative solvent saturation at the spray dryer outlet. The prediction quality is similar to that of a four-variable regression with the spray liquid rate, spray dryer outlet temperature, and its condenser temperature as the predictors. Analyses of the spray dried dispersions morphology and compression characteristics suggest that the bulk density-relative saturation correlation may be the result of the drying kinetics accompanying the particle formation process: while the general morphology of the spray dried materials is predominantly the hollow-sphere type and remains the same regardless of the spray drying parameters, materials produced at higher relative saturation appear to exhibit a thicker shell as a result of slower drying. The lower compressibility of these materials further confirms this observation.