(624b) Simplifying Tablet Film-Coating Process-Scaleup and Transfer through Droplet-Size Measurement

Objective

Describe a simple method of using laser diffraction for droplet-size measurement to characterize coating gun performance and simplify scaling and transfer of pharmaceutical film-coating processes. 

Introduction/Background

Scale-up of pharmaceutical tablet film-coating often involves using a variety of two-fluid coating guns which have very different coating-suspension atomization characteristics and which may rely on different control parameters (atomization pressure vs. atomization air flow).  Still, the film-coating suspension droplet size may deemed low risk and receive little attention during process development until coating problems are detected at the pilot and manufacturing scales.  Vendor data on coating gun performance may be incomplete or too generalized for direct use in specific applications.  Laser diffraction can readily be used to determine the spray characteristics  produced by different guns over a range of process conditions.  This approach provides data that allow matching of droplet size across scales and elimination of droplets size as a variable in scaleup considerations.

Methods

Several coating guns (spray nozzles) from commercially available coating pans were compared using film-coating suspensions with varied composition and concentration.  The viscosity and refractive index of each suspension was measured and recorded.  The guns were mounted above a Malvern Spraytec open-frame laser-diffraction system.   The guns were positioned at a range of heights above the laser beam to simulate typical gun-to-bed distance in coating applications.  A spray was produced over a range of liquid spray rates, atomization air pressures, atomization air flow rates, pattern air pressures, and pattern air flows which mimicked actual process conditions.  The spray was measured over a 5 second period using a capture rate of 50 Hz.  The resulting 250 measurements per run were averaged to provide a droplet-size distribution histogram and D10,D50, and D90 data for each condition.  The droplet-size results were compared between guns and with respect to available vendor nozzle data.  The data allowed determination of parameter setpoints for each coating gun which could produce a given target droplet size.

Results

Matching droplet size between guns was possible. Data was reproducible with a tolerance of approximately 2 to 3 microns.  D₅₀ appeared to be the most reliable and repeatable characteristic of the distribution.  Suspension viscosity played a major role in droplet size.  Pattern air had some influence on the droplet size for given conditions.  Nozzle height had no effect to a minor effect on droplet size, though a slight increase in droplet size was observed at increasing heights. 

Droplet size was measured by mimicking atomization for a tablet-coating process which previously was restricted to low spray rates and had produced a visually rough film coating (Process A).  The measurements indicated the droplet sizes being produced were larger than those produced on different coating equipment where the process had been run successfully and robustly  (Process B).  The atomization parameters for Process A were adjusted until the coating gun produced droplets similar in size to those produced in Process B.  Process A was then successfully run at a higher spray rate using the new atomization parameters. 

Conclusions

Laser diffraction can be used to provide simple performance data that allows comparison of droplets produced by coating guns across scales and manufacturers.

Implications

This approach can be used to provide droplet-size data that lowers the risk associated with scaleup and transfer of film-coating sprays.