(230d) Modeling of the Secondary Drying and the Fate of Organic Solvents for Spray Dried Dispersion (SDD) Product

The spray dryer has been used to generate amorphous dispersions of API and polymer to enhance the solubility and bioavailability of drugs that are less water soluble.  This powder, after spray drying, contains residual solvents and they need to be further removed to an acceptable limit in a secondary dryer.  The purpose of this study is to understand the secondary drying mechanism and establish a model to predict the drying performance for scale-up and the fate of organic solvents.

The kinetics of solvent removal from Spray Dried Dispersion (SDD) product follows the Fickian diffusion behavior.  Since the SDD particles are typically hollow and the shell thickness of the hollow bead is typically between 10-15% of the diameter of the bead, the effect of curvature can be neglected.  Hence, a diffusion equation for the geometry of a slab as an approximation was used for modeling the secondary drying.  Excellent agreement is obtained between the experimental data and the prediction from the modeling.  The control parameters of the secondary drying are the diffusion coefficient and the diffusion length.  Since the diffusion coefficient is a function of temperature only, the secondary drying performance is not scale dependent.  This secondary drying has been successfully scaled up from a lab scale of a few grams to a bench scale of 500 grams in an agitated conical dryer and the large-scale drying kinetics follow the model prediction well.  The fate of residual solvents including acetone, methanol and others can be successfully determined from this modeling work.