title: Improvement of dissolution rates of poorly water soluble APIs using novel spray freezing into liquid technology.
abstract: OBJECTIVE
  To develop and demonstrate a novel particle engineering technology, spray freezing into liquid (SFL), to enhance the dissolution rates of poorly water-soluble active pharmaceutical ingredients (APIs).
  
  
  METHODS
  Model APIs, danazol or carbamazepine with or without excipients, were dissolved in a tetrahydrofuran/water cosolvent system and atomized through a nozzle beneath the surface of liquid nitrogen to produce small frozen droplets, which were subsequently lyophilized. The physicochemical properties of the SFL powders and controls were characterized by X-ray diffraction, scanning electron microscopy (SEM), particle size distribution, surface area analysis, contact angle measurement, and dissolution.
  
  
  RESULTS
  The X-ray diffraction pattern indicated that SFL powders containing either danazol or carbamazepine were amorphous. SEM micrographs indicated that SFL particles were highly porous. The mean particle diameter of SFL carbamazepine/SLS powder was about 7 microm. The surface area of SFL danazol/poloxamer 407 powder was 11.04 m2/g. The dissolution of SFL danazol/poloxamer 407 powder at 10 min was about 99%. The SFL powders were free flowing and had good physical and chemical stability after being stored at 25 degrees C/60%RH for 2 months.
  
  
  CONCLUSIONS
  The novel SFL technology was demonstrated to produce nanostructured amorphous highly porous particles of poorly water soluble APIs with significantly enhanced wetting and dissolution rates.
authors.affiliation: Division of Pharmaceutics, College of Pharmacy, The University of Texas at Austin, 78712, USA.
authors.forename: Jiahui
authors.initials: J
authors.lastname: Hu
authors.forename: True L
authors.initials: TL
authors.lastname: Rogers
authors.forename: Judith
authors.initials: J
authors.lastname: Brown
authors.forename: Tim
authors.initials: T
authors.lastname: Young
authors.forename: Keith P
authors.initials: KP
authors.lastname: Johnston
authors.forename: Robert O
authors.initials: RO
authors.lastname: Williams
mesh_terms: D004339:Drug Compounding; D005615:Freezing; D010316:Particle Size; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000295:instrumentation / Q000379:methods*; D014867:Water / Q000737:chemistry*
chemical_list: D004364:Pharmaceutical Preparations; D014867:Water