Time scale based analysis of in-situ crystal formation in droplet undergoing rapid dehydration

The surface structure of crystalline particles affects the functionality of the particles in drug delivery. Prediction of the final structure of particles that crystallize easily within the spray drying process is of interests for many applications. A theoretical framework was developed for the prediction of crystal structure precipitating on the surface of the particle. This model was based on the dimensionless Damkohler number (Da), to be an indicator of final particle morphology. Timescales of evaporation and reaction were required for calculation of the Damkohler number. The modified evaporation time scale was estimated based on the time that is available for the crystal to precipitate after supersaturation. The reaction time scale was estimated based on the time scale for induction time. Mannitol was produced under different processing conditions in order to validate the theoretical model. Results showed for the high Damkohler numbers, the surface structure of the particle was rough, while smaller Damkohler numbers led to relatively smooth particle surfaces. Additionally, although the beta polymorph was dominant in all of the experiments, alpha polymorph was precipitated in the experiments with a large Damkohler number. The theoretical framework developed will be a useful predictive tool to guide the manipulation of particle crystallization in spray dryers.