Computational Fluid Dynamics (CFD) Simulations of Spray Drying: Linking Drying Parameters with Experimental Aerosolization Performance

• Published in: Pharmaceutical research Vol. 37; no. 6; p. 101
• Main Authors: Longest, P. Worth, Farkas, Dale, Hassan, Amr, Hindle, Michael
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.06.2020; Springer; Springer Nature B.V
• Subjects: Administration, Inhalation; Aerosols; Analysis; Biochemistry; Biomedical and Life Sciences; Biomedical Engineering and Bioengineering; Biomedicine; Chemistry, Pharmaceutical; Computer applications; Computer Simulation; Drug Compounding - methods; Dry Powder Inhalers; Drying; Excipients - chemistry; Fluid dynamics; Hydrodynamics; Inhalers; L-leucine; Leucine; Mass transfer; Medical Law; Models, Chemical; Particle Size; Pharmacology/Toxicology; Pharmacy; Research Paper; Simulation methods; Spray Drying; Dry powder inhaler; drying parameters; excipient enhanced growth aerosol formulations; particle engineering; pharmaceutical engineering; respiratory drug delivery
• ISSN: 0724-8741; 1573-904X
• DOI: 10.1007/s11095-020-02806-y

Purpose The purpose of this study was to develop a new computational fluid dynamics (CFD)-based model of the complex transport and droplet drying kinetics within a laboratory-scale spray dryer, and relate CFD-predicted drying parameters to powder aerosolization metrics from a reference dry powder inhaler (DPI). Methods A CFD model of the Buchi Nano Spray Dryer B-90 was developed that captured spray dryer conditions from a previous experimental study producing excipient enhanced growth powders with L-leucine as a dispersion enhancer. The CFD model accounted for two-way heat and mass transfer coupling between the phases and turbulent flow created by acoustic streaming from the mesh nebulizer. CFD-based drying parameters were averaged across all droplets in each spray dryer case and included droplet time-averaged drying rate (κ avg ), maximum instantaneous drying rate (κ max ) and precipitation window. Results CFD results highlighted a chaotic drying environment in which time-averaged droplet drying rates (κ avg ) for each spray dryer case had high variability with coefficients of variation in the range of 60–70%. Maximum instantaneous droplet drying rates (κ max ) were discovered that were two orders of magnitude above time-averaged drying rates. Comparing CFD-predicted drying parameters with experimentally determined mass median aerodynamic diameters (MMAD) and emitted doses (ED) from a reference DPI produced strong linear correlations with coefficients of determination as high as R 2  = 0.98. Conclusions For the spray dryer system and conditions considered, reducing the CFD-predicted maximum drying rate experienced by droplets improved the aerosolization performance (both MMAD and ED) when the powders were aerosolized with a reference DPI.