The morphology of spray dried mannitol particles — The vital importance of droplet size

As the morphology of spray dried aqueous mannitol solutions is strongly influenced by the scale of the used spray dryer or more correctly by the droplet size generated in the spray dryer the purpose of this work is to carefully study and compare the morphologies and underlying particle formation mechanisms on lab and pilot scale. Therefore drying experiments of 15% [w/w] aqueous mannitol solutions were performed on a lab and pilot scale spray dryer at different outlet temperatures. The obtained spray dried products are intended to be used as carrier particles for pulmonary drug delivery. In order to show that the morphology is highly dependent on the initial droplet size, irrespective of the size of the used spray dryer, droplets of different size were dried in the pilot scale spray dryer at different air outlet temperatures. Additionally the influence of feed temperature on particle morphology was studied.For small droplets crystallization from a highly viscous liquid or even water-free melt is observed, leading to rough particles at high outlet temperatures and smooth particles at low temperatures. When drying larger droplets, however crystallization obviously starts from a more diluted solution leading to rougher surfaces, containing larger single crystals at lower outlet temperatures than at higher ones. For large droplets an increase in the mannitol solution feed temperature leads to particles of comparably rougher surface. No influence of feed temperature was observed for smaller droplets.

This work shows that particle morphology of spray dried mannitol, especially surface roughness, largely depends on the initial droplet size. Depending on the droplet size, two different crystallization regimes of aqueous mannitol solutions can be observed; either crystallization from a solution or delayed crystallization from a highly supersaturated viscous liquid or even water-free melt.Figure optionsDownload as PowerPoint slideHighlights
► Particle morphology of spray dried mannitol depends on the initial droplet size.
► For small particles (droplets) rough surfaces are observed at high temperatures.
► For large particles (droplets) rough surfaces are observed at low temperatures.
► Depending on the droplet size there are two different crystallization regimes.
► We show that mannitol particle morphology changes during scale-up.