(64d) Investigation of Single-Droplet Drying Kinetics in an Acoustic Levitator, Micro-Sphere Morphology and Mechanical Properties of Pharmaceutical Excipients

In the last years there has been significant interest in advanced continuous manufacturing of pharmaceuticals. These manufacturing routes have significant advantages, including a smaller plant footprint (smaller equipment and facilities), reduced manufacturing time, elimination of unnecessary storage by streamlined production from start to finish, and lower manufacturing costs. Moreover, quality is ensured in real time, leading to a better overall efficiency of the manufacturing process.

One of the challenges in continuous production is the link between primary (API synthesis, crystallization, purification, filtration and drying) and secondary manufacturing (blending, granulation and tableting/capsule filling). Particle properties of crystalline APIs are tailored in primary manufacturing by wet chemical processes. To enable further processing of the crystalline API in secondary manufacturing, a drying step is necessary to remove the residual solvents.

One route to transform a fluid feed stream into dry powders is spray drying. A major benefit of spray drying over other technologies is that drying is conducted close to the wet bulb temperature of the slurry, and therefore it is suitable for heat-sensitive products. As long as the surface of a droplet/particle is covered with a liquid layer, drying occurs at the wet bulb temperature in the first drying stage. This liquid layer is removed by evaporation of the liquid phase of the slurry into the drying air until solidification occurs. Afterwards, drying progresses in the second drying stage at temperatures converging to the dry bulb temperature until the designed residual moisture content is reached.

In suspensions, solids are dissolved in the carrier liquid and suspended as particles. The drying of suspension slurries results in precipitation of dissolved material forming bridges between the primary particles. Therefore, the final microsphere properties are influenced by the amount of dissolved solids, since this determines the size and amount of bridges between primary particles. There is a clear correlation between more dissolved material in the slurry liquid and the formation of stronger bridges between primary particles. This alters significantly the final microsphere properties, as well as the corresponding processability.

In this work we focus on the correlation between slurry composition and the resulting material properties after drying. Drying experiments were conducted by acoustic levitation of a model compound in binary liquid mixture droplets. The acoustic levitation setup enabled microscopic observations of the drying behavior of single droplets. Variations in the suspension composition revealed the impact on the drying kinetics as well as the mechanical properties and the morphology of the final particles (microspheres). Different microsphere morphologies were observed, from very loose agglomerates to densely packed microspheres with crust formation. Electron micrographs of the microsphere morphology of different suspension compositions were in good agreement with the hardness measured by a compression strength test.