A novel particle engineering technology: spray-freezing into liquid.

Spray-freezing into liquid (SFL) is a novel particle engineering technology where a feed solution containing an active pharmaceutical ingredient (API) and pharmaceutical excipient(s) is atomized beneath the surface of a cryogenic liquid, such as liquid nitrogen. Intense atomization results from the impingement that occurs between the liquid feed and the cryogenic liquid. The atomized feed droplets instantly solidify within the liquid nitrogen continuous phase to form a suspension. The frozen microparticles are then collected and lyophilized to obtain the dry SFL micronized powder. The novel SFL process has been used in this study to enhance the dissolution rates of two poorly water soluble APIs, carbamazepine and danazol. The SFL process has also been used to produce stable peptide particles of insulin.