title: Comparison between hot-melt extrusion and spray-drying for manufacturing solid dispersions of the graft copolymer of ethylene glycol and vinylalcohol.
abstract: OBJECTIVE
  To investigate the effect of the manufacturing method (spray-drying or hot-melt extrusion) on the kinetic miscibility of miconazole and the graft copolymer poly(ethyleneglycol-g-vinylalcohol). The effect of heat pre-treatment of solutions used for spray-drying and the use of spray-dried copolymer as excipient for hot-melt extrusion was investigated.
  
  
  METHODS
  The solid dispersions were prepared at different drug-polymer ratios and analyzed with modulated differential scanning calorimetry and X-ray powder diffraction.
  
  
  RESULTS
  Miconazole either mixed with the PEG-fraction of the copolymer or crystallized in the same or a different polymorph as the starting material. The kinetic miscibility was higher for the solid dispersions obtained from solutions which were pre-heated compared to those spray-dried from solutions at ambient temperature. Hot-melt extrusion resulted in an even higher mixing capability. Here the use of the spray-dried copolymer did not show any benefit concerning the kinetic miscibility of the drug and copolymer, but it resulted in a remarkable decrease in the torque experienced by the extruder allowing extrusion at lower temperature and torque.
  
  
  CONCLUSIONS
  The manufacturing method has an influence on the mixing capacity and phase behavior of solid dispersions. Heat pre-treatment of the solutions before spray-drying can result in a higher kinetic miscibility. Amorphization of the copolymer by spray-drying before using it as an excipient for hot-melt extrusion can be a manufacturing benefit.
authors.affiliation: Laboratory for Pharmacotechnology and Biopharmacy, Catholic University of Leuven, Gasthuisberg O&N2, Herestraat 49, Box 921, 3000 Leuven, Belgium.
authors.forename: Sandra
authors.initials: S
authors.lastname: Guns
authors.forename: Aswin
authors.initials: A
authors.lastname: Dereymaker
authors.forename: Pieterjan
authors.initials: P
authors.lastname: Kayaert
authors.forename: Vincent
authors.initials: V
authors.lastname: Mathot
authors.forename: Johan A
authors.initials: JA
authors.lastname: Martens
authors.forename: Guy
authors.initials: G
authors.lastname: Van den Mooter
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods*; D006358:Hot Temperature; D011092:Polyethylene Glycols / Q000032:analysis / Q000138:chemical synthesis; D011108:Polymers / Q000138:chemical synthesis; D011145:Polyvinyls / Q000138:chemical synthesis*; D012996:Solutions; D014753:Vinyl Compounds / Q000138:chemical synthesis; D014961:X-Ray Diffraction / Q000379:methods
chemical_list: C519734:Kollicoat IR; D011108:Polymers; D011145:Polyvinyls; D012996:Solutions; D014753:Vinyl Compounds; D011092:Polyethylene Glycols