Dimensional analysis of in-situ crystal formation in droplet undergoing rapid dehydration.

The surface structure of the crystalline particles affects the functionality of the particles in drug delivery. Prediction of the final structure of particles that crystallize easily within the spray dryer is of interests of many applications. A theoretical framework was developed for the prediction of crystal structure precipitating on the surface of the particle. Mannitol was produced under different processing conditions in order to validate the theoretical model. The theoretical framework was developed 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. Results showed for the high Damkohler number, Da≈>1, the surface structure of the particle is rough, while the minor Damkohler showed relatively smooth surface. Additionally, though the beta polymorph was dominant in all of the experiments, alpha polymorph was precipitated in the experiments with a large Damkohler number. Therefore, this model could be a useful tool for prediction of final structure and polymorph.