Active freeze drying for production of nanocrystal-based powder: A pilot study

Active Freeze Drying allows for producing lyophilised powders by progressive agitation of frozen blocks undergoing sublimation. One potential application of this process is the formulation design of unstable nanosuspensions for oral drug delivery, as here shown for nanocrystal-based ketoconazole powder. With this technique, a critical vapour flow needs to be achieved in order to obtain reasonable process yields (> 78%). The size distribution of powder particles (median size between 21 and 44 mu m) was affected by the nanocrystal concentration and the drug-to-stabilizer ratio. This was assumed to be related to the mechanical strength of the solid network from which the powder particles break off. The adjustments of the drug-to-stabilizer ratio and the freezing procedure proved to play a major role in improving powder redispersibility. However, differences in powder redispersibility did not translate into significant changes in in-vitro dissolution rates. Active Freeze Drying has confirmed to be a promising tool to efficiently produce redispersible nanocrystal powders.