(671d) Investigation of Microsphere Strength for Spray Drying Applications By Means of Acoustic Levitation

M. Kreimer¹, I. Aigner¹, S. Sacher¹, M. Krumme², T. Mannschott², P. van der Wel³,
A. Kaptein³, H. Schröttner^4,5, G. Brenn⁶, J.G. Khinast^1,7

¹ Research Center Pharmaceutical Engineering (RCPE) GmbH, Inffeldgasse 13, 8010 Graz, Austria

² Novartis Pharma AG, Novartis Campus, 4056 Basel, Switzerland

³ Hosokawa Micron B.V., Gildenstraat 26, 7005 BL Doetinchem, Netherlands

⁴ Graz University of Technology, Institute for Electron Microscopy and Nanoanalysis, Steyrergasse 17, 8010 Graz, Austria

⁵ Austrian Centre for Electron Microscopy and Nanoanalysis (FELMI-ZFE), Steyrergasse 17, 8010 Graz, Austria

⁶ Graz University of Technology, Institute of Fluid Mechanics and Heat Transfer, Inffeldgasse 25 F, 8010 Graz, Austria

⁷ Graz University of Technology, Institute for Process and Particle Engineering, Inffeldgasse 13, 8010 Graz, Austria

Growing demands on flexibility and agility in the production of pharmaceutical compounds have led to a paradigm shift, away from batch processing towards advanced continuous manufacturing. Continuous production of solid oral dosage forms starts with API synthesis, continuing with crystallization, purification, filtration, drying, blending, granulation and typically ends via tableting/capsule filling.

While tableting is a continuous process, several other unit operations currently exist mainly in batch mode. One example is the drying of crystals. However, spray drying is a commonly used technology to transform a fluid feed stream into dry powders. An advantage of spray drying is that it can be applied even to heat-sensitive products, since drying occurs close to the wet bulb temperature. Moreover, solutions and suspensions can be dried by evaporation of the liquid phase in a gaseous drying medium.

In the case of spray drying of suspensions, the objective is not to change material properties, such as particle size distribution. However, after crystallization, washing and filtration, different amounts of dissolved solids are present in the suspension slurry. During spray drying of the slurry, the dissolved material will solidify and form solid bridges between the suspension particles. Clearly, the amount of the dissolved material has a crucial impact on the final particle properties. The more material is dissolved in the slurry, the larger and stronger the bridges between primary particles will be. This has significant impact on the final particle properties and the associated processability.

This work highlights the influence of suspension composition on the material properties after drying. Drying of a model compound in a binary-liquid mixture was studied via acoustic levitation. This method enabled observations of the drying behavior of single droplets on a microscopic scale. Changes in the suspension composition had a strong impact on the mechanical properties and morphology of the final particles (microspheres). The morphology varied from very loose agglomerates to densely packed microspheres with crust formation. Hardness of single microspheres was measured via a compression strength test and correlated to the suspension composition.