Interplay of solute crystallization and drying potential in controlling spray dried particle morphology

Spray drying is widely used in pharmaceutical manufacturing to engineer particles with controlled morphology and solid state properties, which critically influence formulation performance. Particle morphology is commonly interpreted through the Péclet number framework, which links solvent evaporation and solute diffusion. The influence of drying processes, especially drying temperature, on particle morphology has been investigated in the literature, and discrepant observations have been reported, which could be due to differences in processing conditions and the complexity of formulation systems. To better understand the impact of drying conditions on particle morphology, we systematically investigated particle morphology evolution by manipulating drying potential-inlet temperature and airflow rate-while minimizing other process variabiles, using a single component, simple system. A single model drug, ciprofloxacin, in two salt forms-sodium ciprofloxacin and ciprofloxacin hydrochloride-with distinct crystallization tendencies but comparable diffusional properties was used. The present work investigates the effect of inlet temperature, airflow rate, and solute crystallization tendency on particle morphology. We observed that particle morphology and size are governed by the interplay between evaporation conditions and solute solidification kinetics. Solute crystallization tendency strongly dictates shell formation and surface morphology. In addition, the inlet temperature effects depend critically on airflow rate and resulting outlet conditions. These findings show that inlet temperature alone is an insufficient predictor of particle morphology. This work provides a mechanistic framework for rational particle design by integrating drying intensity with solute solid-state behaviour.