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

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Abstract

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 (κavg), maximum instantaneous drying rate (κmax) and precipitation window.

Results

CFD results highlighted a chaotic drying environment in which time-averaged droplet drying rates (κavg) for each spray dryer case had high variability with coefficients of variation in the range of 60–70%. Maximum instantaneous droplet drying rates (κmax) 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 R2 = 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.

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Abbreviations

3D:

Three dimensional

AS:

Albuterol sulfate

CFD:

Computational fluid dynamics

CV:

Coefficient of variation

DPI:

Dry powder inhaler

ED:

Emitted dose

EEG:

Excipient enhanced growth

HPLC:

High performance liquid chromatography

HPMC:

Hydroxypropyl methylcellulose

ISR:

Time integral of saturation ratio

LPM:

Liters per minute

LRN:

Low Reynolds number

MMAD:

Mass median aerodynamic diameters

MN:

Mannitol

MT:

Mouth-throat

NGI:

Next Generation Impactor

RH:

Relative humidity

RMM:

Rapid mixing model

SD:

Standard deviation

SR:

Saturation ratio

T:

Temperature

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Authors and Affiliations

  1. Department of Mechanical and Nuclear Engineering, Virginia Commonwealth University, 401 West Main Street, P.O. Box 843015, Richmond, VA, 23284-3015, USA

    P. Worth Longest & Dale Farkas

  2. Department of Pharmaceutics, Virginia Commonwealth University, Richmond, VA, USA

    P. Worth Longest, Amr Hassan & Michael Hindle

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  1. P. Worth Longest
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Longest, P.W., Farkas, D., Hassan, A. et al. Computational Fluid Dynamics (CFD) Simulations of Spray Drying: Linking Drying Parameters with Experimental Aerosolization Performance. Pharm Res 37, 101 (2020). https://doi.org/10.1007/s11095-020-02806-y

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