Continuous and scalable process for water-redispersible nanoformulation of poorly aqueous soluble APIs by antisolvent precipitation and spray-drying.

This work investigates the technical feasibility of formulating water-redispersible nanocrystals of a poorly aqueous soluble drug by a continuous and scalable route. By coupling antisolvent precipitation with immediate spray-drying, fenofibrate nanoparticles were precipitated and formulated into a dry powder form containing lactose or mannitol as redispersant, hydroxylpropyl methyl cellulose (HPMC) and sodium dodecyl sulfate (SDS) as stabilizers. Field emission scanning electron microscopy (FESEM) and dynamic laser light scattering (DLLS) showed that nanosized fenofibrate were observed both upon precipitation and after the formulated powder was reconstituted in water. Analyses with powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC) showed that the formulated drug remained predominantly in the crystalline state. USP dissolution testing in 0.1N HCl solution with 0.5% (w/w) Tween-80 showed that the nanocrystals could be readily redispersed upon reconstitution and exhibited significantly a higher dissolution rate with 84.2% drug dissolved in 5 min as compared to the conventional spray-dried formulation (31.7%) and the physical mixture (9.7%) using micronized fenofibrate. The results suggest the potential of combining static mixing and spray drying for large-scale continuous production of pharmaceutical nanoformulations.