Ultrasonic spray freeze-drying of sucrose and mannitol-based formulations: Impact of the atomization conditions on the particle morphology and drying performance

Tailoring Dry Microparticles for Pulmonary Drug Delivery: Ultrasonic Spray Freeze-Drying with Mannitol and Salbutamol Sulphate

“…The morphology of MPs for different mannitol concentrations and feed flow rates was observed from the SEM images, reported in Figure 1. In accordance with previous studies [35,36,39], SFD MPs appeared as highly porous spheres and this structure was maintained for all the investigated conditions. The high porosity is ascribable to the high freezing rate reached during the process, which induc- In accordance with previous studies [35,36,39], SFD MPs appeared as highly porous spheres and this structure was maintained for all the investigated conditions.…”

“…In accordance with previous studies [35,36,39], SFD MPs appeared as highly porous spheres and this structure was maintained for all the investigated conditions. The high porosity is ascribable to the high freezing rate reached during the process, which induc- In accordance with previous studies [35,36,39], SFD MPs appeared as highly porous spheres and this structure was maintained for all the investigated conditions. The high porosity is ascribable to the high freezing rate reached during the process, which induces the formation of small ice crystals and, hence, small pores, in great numbers [25].…”

“…The ANOVA highlighted statistically significant differences among the mean d g obtained at equal solid content, except for some values associated with the flow rates closest to each other, i.e., 10 and 7.5 or 2.5 and 1 mL/min. This clear dependence of the particle size on the feed flow rate was also detectable from the SEM images shown in Figure 1 and this was consistent with results from previous studies [39]. The same trend could be detected also for the d ae (Figure 2B), being directly proportional to the d g (Equation ( 1)).…”

“…In fact, increasing the flow rate led to a mean particle size growing from 32 to 53 μm at 5% (w/w) mannitol, from 34 to 58 μm at 10% (w/w) mannitol, from 33 to 57 μm at 15% (w/w) mannitol, and from 36 to 68 μm at 20% (w/w) mannitol. The growing flow rate was responsible for the thickening of the liquid film that formed on the vibrating tip of the ultrasonic nozzle prior to atomisation, causing a larger d [39]. The ANOVA highlighted statistically significant differences among the mean d obtained at equal solid content, except for some values associated with the flow rates closest to each other, i.e., 10 and 7.5 or 2.5 and 1 mL/min.…”

“…However, for the d g , this phenomenon was less visible: p < 0.001 for 20% vs. 5%, 20% vs. 10%, 15% vs. 10%, and 10% vs. 5%; p = 0.013 for 20% vs. 15%; and the comparison between 15% and 10% had no statistically significant difference (p = 0.375). The slight increase in the d g with the solid content was probably due to the increasing viscosity of the solution [39]. Conversely, the increase of the d ae at growing solid concentrations was more pronounced than that of d g (p < 0.001 for all the comparisons) due to the dependence of the d ae on the particle's mass density (Equation ( 1)).…”