Production of amorphous nanoparticles by supersonic spray-drying with a microfluidic nebulator

Abstract

Amorphous nanoparticles (a-NPs) have physicochemical properties distinctly different from those of the corresponding bulk crystals; for example, their solubility is much higher. However, many materials have a high propensity to crystallize and are difficult to formulate in an amorphous structure without stabilizers. We fabricated a microfluidic nebulator that can produce amorphous NPs from a wide range of materials, even including pure table salt (NaCl). By using supersonic air flow, the nebulator produces drops that are so small that they dry before crystal nuclei can form. The small size of the resulting spray-dried a-NPs limits the probability of crystal nucleation in any given particle during storage. The kinetic stability of the a-NPs—on the order of months—is advantageous for hydrophobic drug molecules.

Crystallization of undercooled liquid fenofibrate

“…The last junction is three-dimensional (3D) 10 to push the ethanol films away from all four walls of the last part of the main channel, thereby breaking the ethanol films into very small drops that rapidly dry. 8 We use fenofibrate as a hydrophobic model drug; amorphous fenofibrate is an undercooled liquid at room temperature since it has a glass transition temperature, T g , of À20 1C 7 and a melting temperature, T m , of 80 1C. 11 We dissolve fenofibrate in ethanol at 5 mg ml À1 , and inject the solution through one liquid inlet at 1 ml h À1 using syringe pumps; we block the second liquid inlet to avoid leakage of the liquid and the air.…”

“…We introduce air by applying 0.28 MPa to all the air inlets and collect the spray dried undercooled liquid drops 15 cm apart from the nozzle on a flat substrate. 8 The nebulator produces amorphous undercooled liquid fenofibrate drops with diameters as small as 14 nm; 12 the volume of a single drop is as low as 10 À21 l. However, as amorphous fenofibrate is an undercooled liquid at room temperature, drops coalesce as soon as they come in contact with each other. The larger volume of the resulting coalesced drops increases the probability for a crystal nucleus to form in each drop.…”

“…Well-separated drops as small as 10 À21 l remain liquid for more than 7 months if stored at room temperature. 8 If we increase the volume of the drops to 0.1-1 pl, they show no sign of crystallinity after 1 day storage in an aluminum DSC pan, as indicated by the absence of any melting peaks in DSC trace 1 of Fig. 2.…”

Using electric current to surpass the microstructure breakup limit

“…Fabrication of nanoscale grains1, droplets23 and bubbles4 has attracted significant attentions in recent decades. Microstructure refinement toward the generation of nanostructured materials is an attractive mean5.…”

Composition inversion to form calcium carbonate mixtures

“…This result is in accordance with the fact that the production of amorphous sodium chloride powder needs very special conditions and has so far been observed after water evaporation from nanometer-sized droplets. 36,37 XRD measurements of all reaction products obtained under the various conditions listed in the experimental part confirm the completeness of the reaction and composition of the reaction product to be a halite-calcite mixture (cf. XRD data given in the ESI, † Fig.…”