(T1330-06-33) Extensive Characterization of Spray Dry Solution Atomization for HPMCAS Placebo Solutions by Optical Patternation, Phase Doppler Analysis, and Spray Velocity

Purpose: Spray Drying is a preferred technique for generating amorphous solid dispersions due to its compatibility with a variety of material properties and ability to tailor particle properties. Atomization of the spray solution is a critical part of the spray drying process and contributes significantly to the resulting particle size and morphology. Maintaining similar spray solution atomization is a central tenet of process transfer and scale up, so characterization of spray solution atomization is essential for understanding the spray drying process. Spray Dried Compound A underwent two process changes that were expected to impact the atomization behavior: a switch in the spray solution composition and a nozzle change. This poster probes the impact of these changes on atomization characterizations of two placebo solutions which were selected to match the viscosity of the active spray dry solution. The solvent mixtures were also studied to understand the impact of polymer loading.

Methods: Two spray drying placebo solutions were selected for this study: Solution Mixture 1 and Solution Mixture 2. These two placebo solutions match the viscosity and polymer loading of two spray drying solutions of compound A. Two common pressure swirl spray drying nozzles were selected ( Schlick 121V 45° 0.3 mm and Schlick 121V 60° 0.25 mm) and operated across a range of pressures (200-1450 PSI) during the measurements. Measurements were taken at either 30 or 50 mm away from the nozzle orifice. Spray patternator measurements were taken using a SETscan OP-600 optical patternator at either 30 or 50 mm away from the nozzle orifice. Phase Doppler Analysis Measurements are collected with a 2D system from Dantec Dynamics. The droplet sizes were compared to particle size measurements of compound A taken by laser diffraction. Spray velocity measurements were taken using high-speed video with a Motion Studio N4 camera at 10,000 frames per sec. Average velocities were estimated from video having 3,000 frames collected at 10kHz and processed to obtain the velocity field in the spray. Compound A was spray dried on a mobile minor spray dryer and the particle size of the resulting spray dried particles were measured by laser diffraction.

Results: The spray patternation measurements yielded several unanticipated results. The two Schlick nozzles selected for this study were pressure swirl nozzles and were expected to yield a hollow cone atomization pattern (Figure 1, left) when properly atomized. However, this pattern was not observed with the Schlick nozzles across the operating range. Highly heterogenous patterns were obtained with the highest spray densities in the center of the spray (Figure 1 right). The spray pattern variability decreased as the spray solution viscosity increased, with less variability observed with the two solution mixtures compared to the pure solvents. The droplet size of the Solution Mixture 1 is obtained for both nozzles across the operating pressure range (Figure 2). A relatively narrow droplet size range of ~16-38 µm was obtained for both nozzles with no major changes in droplet size as a result of the different orifice sizes. This droplet data was confirmed by the particle size data for compound A, which showed that switching between the two nozzles has no major impact on particle size distribution. The effect of switching from Solution Mixture 1 to Solution Mixture 2 to was studied using the Schlick 0.3 mm nozzle. These two placebo solutions were chosen to have similar viscosities which should yield similar particle size distributions. The droplet size data bears this hypothesis out with a slight difference (~4-5 µm) in droplet size between the two solutions. Particle size data for compound A also demonstrate that switching the solvent system yields slight differences in particle size distribution. The analyzed spray velocity data shows high velocity regions that visually correlate with the sheet region of the spray (prior to break up and droplet formation) and appeared to extend up to 30 mm from the nozzle orifice at lower pressures. High velocity regions are also observed in the center of the spray which are markedly more pronounced at high pressures.

Conclusion: The knowledge gained through this study yielded several surprising insights into spray drying atomization. For the patternator analysis, large difference in nozzle behavior were observed compared to the expected behavior. There did not appear to be a significant change in droplet size as a function of atomization pressure, which suggested the spray drying particle size could be fairly robust as a function of nozzle pressure in these two nozzles. The droplet sizes also matched the particle sizes for compound A. The spray velocity measurements and videos illustrated a longer than expected length of sheet.

>br>Figure 1: (Left): Example optical patternation pattern for a pressure swirl nozzle demonstrating hollow cone behavior. (Right): Optical Patternation pattern observed from Schlick 0.3 mm nozzle spraying Soluton Mixture 1 at 1100 PSI


Figure 2: Dv50 (µm) as a function of nozzle pressure for Schlick 0.25mm (blue) and Schlick 0.3 mm (red) nozzles spraying Solution Mixture 1