Particle concentrations of formulations after 0, 1, 3, and 5 freeze-thaw cycles. With increasing numbers of freeze-thaw cycles, a decrease in 5–10 µm particles was detected and an increase in larger particles was seen. Particle size ranges are 5–10 µm (black), 10–20 µm (dark gray), 20–30 µm (light gray), 30+ µm (white).