title: Influence of solvent composition on the miscibility and physical stability of naproxen/PVP K 25 solid dispersions prepared by cosolvent spray-drying.
abstract: OBJECTIVE
  To investigate the influence of solvent properties on the phase behavior and physical stability of spray-dried solid dispersions containing naproxen and PVP K 25 prepared from binary cosolvent systems containing methanol, acetone and dichloromethane.
  
  
  METHODS
  The viscosity, polymer globular size and evaporation rate of the spray-drying feed solutions were characterized. The solid dispersions were prepared by spray-drying drug-polymer solutions in binary solvent blends containing different proportions of each solvent. The phase behavior was investigated with mDSC, pXRD, FT-IR and TGA. Further, physical stability of solid dispersions was assessed by analyzing after storage at 75% RH.
  
  
  RESULTS
  The solid dispersions prepared from solvent/anti-solvent mixture showed better miscibility and physical stability over those prepared from the mixtures of good solvents. Thus, solid dispersions prepared from dichloromethane-acetone exhibited the best physicochemical attributes followed by those prepared from methanol-acetone. FT-IR analysis revealed differential drug-polymer interaction in solid dispersions prepared from various solvent blends, upon the exposure to elevated humidity.
  
  
  CONCLUSIONS
  Spray-drying from a cocktail of good solvent and anti-solvent with narrower volatility difference produces solid dispersions with better miscibility and physical stability resulting from the simultaneous effect on the polymer conformation and better dispersivity of drug.
authors.affiliation: Laboratorium voor Farmacotechnologie en Biofarmacie, K.U.Leuven, Leuven, Belgium.
authors.forename: Amrit
authors.initials: A
authors.lastname: Paudel
authors.forename: Guy
authors.initials: G
authors.lastname: Van den Mooter
mesh_terms: D000096:Acetone / Q000737:chemistry; D000336:Aerosols / Q000737:chemistry; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D003890:Desiccation / Q000379:methods; D004355:Drug Stability; D004356:Drug Storage; D006813:Humidity; D000432:Methanol / Q000737:chemistry; D008752:Methylene Chloride / Q000737:chemistry; D008859:Microscopy, Polarization; D009288:Naproxen / Q000737:chemistry*; D010316:Particle Size; D011205:Povidone / Q000737:chemistry*; D033362:Powder Diffraction; D012995:Solubility; D012997:Solvents / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared; D014783:Viscosity
chemical_list: D000336:Aerosols; D000894:Anti-Inflammatory Agents, Non-Steroidal; D012997:Solvents; D000096:Acetone; D009288:Naproxen; D008752:Methylene Chloride; D011205:Povidone; D000432:Methanol