Driving Spray Drying towards Better Yield: Tackling a Problem That Sticks Around.

Powder deposition and accumulation on walls of spray drying chamber has been known to impact spray drying processes, resulting in lower yield, frequent shutdowns, and downtimes. Critical factors that impact the extent and rate of wall deposition have been studied extensively in the chemical and food industry. In this paper, we present an atypical process yield issue wherein acceptable yield is obtained during the first batch of spray drying but undergoes significant yield loss in consecutive batches. Through understanding the interplay of the process, material properties, and equipment, we identify key mechanisms that are playing a role in causing the process yield issue. These mechanisms include surface roughness of the inner wall of the spray dryer, variation in gas flow due to the introduction of process analytical technology, start-up and shutdown operating parameters that expose the wall deposited powder from the prior batch to temperatures close to the onset of glass transition temperature and cause depression of its glass transition temperature. These factors result in more wall accumulation and impact the yield in subsequent batches. By correcting for most of these factors, the yield reduction issue was mitigated, and processing efficiency was improved.

Characterization of Spray Dried Particles Through Microstructural Imaging.

Spray drying is commonly used to produce amorphous solid dispersions (ASD) to improve the bioperformance of poorly water-soluble drugs. In this study, imaging techniques such as focused ion beam-scanning electron microscopy (FIB-SEM) and X-ray microcomputed tomography (XRCT) were used to study the microstructure of spray dried (SD) particles. Spray drying at higher outlet temperature (Tout) was found to produce more spherical hollow particles with smooth surface and thinner walls, while more raisin-like particles with thicker walls were generated at lower Tout. For the first time, an artificial intelligence-facilitated XRCT image analysis tool was developed to make quantitative analysis of thousands of particles individually possible. The particle size distribution through XRCT image analysis is generally in line with what is measured by laser diffraction. The image analysis reveals envelope density as a more sensitive physical attribute for process change than conventional bulk/tap density. Further, the tensile strength of SD particle compacts correlates with the particle wall thickness, and this is likely caused by the larger interparticle contact area generated by more deformation of particles with thinner walls. The knowledge gained here can help enable SD particle engineering and drug product with more robust process and optimized performance.

Transport phenomena in chaotic laminar flows.

In many important chemical processes, the laminar flow regime is inescapable and defines the performance of reactors, separators, and analytical instruments. In the emerging field of microchemical process or lab-on-a-chip, this constraint is particularly rigid. Here, we review developments in the use of chaotic laminar flows to improve common transport processes in this regime. We focus on four: mixing, interfacial transfer, axial dispersion, and spatial sampling. Our coverage demonstrates the potential for chaos to improve these processes if implemented appropriately. Throughout, we emphasize the usefulness of familiar theoretical models of transport for processes occurring in chaotic flows. Finally, we point out open challenges and opportunities in the field.