title: Flocculated amorphous nanoparticles for highly supersaturated solutions.
abstract: OBJECTIVE
  To recover polymer-stabilized amorphous nanoparticles from aqueous dispersions efficiently by salt flocculation and to show that the particles redisperse and dissolve rapidly to produce highly supersaturated solutions.
  
  
  METHODS
  Nanoparticle dispersions of itraconazole stabilized by nonionic polymers were formed by antisolvent precipitation and immediately flocculated with sodium sulfate, filtered and dried. The size after redispersion in water, crystallinity, and morphology were compared with those for particles produced by spray drying and rapid freezing.
  
  
  RESULTS
  Particle drug loading increased to approximately 90% after salt flocculation and removal of excess polymer with the filtrate. The formation of the flocs at constant particle volume fraction led to low fractal dimensions (open flocs), which facilitated redispersion in water to the original primary particle size of approximately 300 nm. Amorphous particles, which were preserved throughout the flocculation-filtration-drying process, dissolved to supersaturation levels of up to 14 in pH 6.8 media. In contrast, both spray dried and rapidly frozen nanoparticle dispersions crystallized and did not produce submicron particle dispersions upon addition to water, nor high supersaturation values.
  
  
  CONCLUSIONS
  Salt flocculation produces large yields of high surface area amorphous nanoparticle powders that de-aggregate and dissolve rapidly upon redispersion in pH 6.8 media, for supersaturation levels up to 14.
authors: Department of Chemical Engineering, The University of Texas at Austin, 1 University Station CO400, Austin, Texas 78712, USA.
authors: Michal E
authors: ME
authors: Matteucci
authors: Joseph C
authors: JC
authors: Paguio
authors: Maria A
authors: MA
authors: Miller
authors: Robert O
authors: RO
authors: Williams Iii
authors: Keith P
authors: KP
authors: Johnston
mesh_terms: D005374:Filtration; D005427:Flocculation; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011108:Polymers / Q000737:chemistry; D012995:Solubility; D012996:Solutions
chemical_list: D011108:Polymers; D012996:Solutions