title: Influence of preparation methods on solid state supersaturation of amorphous solid dispersions: a case study with itraconazole and eudragit e100.
abstract: OBJECTIVE
  The present study aims to determine the drug / polymer miscibility level as a function of the preparation method for an amorphous solid dispersion model system containing itraconazole and eudragit E100. This value was compared to the theoretical crystalline drug solubility in the amorphous polymer and the miscibility of the amorphous drug in the amorphous polymer.
  
  
  METHODS
  The amorphous solid dispersions were prepared via spray drying and film casting in order to evaluate the influence of the solvent drying rate. The experimental miscibility level was estimated using XRPD, MDSC, FT-IR, HPLC and TGA. The solubility and miscibility were estimated using the Flory-Huggins mixing theory and experimental drug in monomer solubility data.
  
  
  RESULTS
  The experimental miscibility level was found to be 27.5% w/w for spray-dried and 15% for film-casted solid dispersions. FT-IR measurements confirmed the absence of saturable interactions like hydrogen bonds, and analysis of the mixed glass transition temperatures suggested low adhesion forces in the amorphous mixture. The solubility analysis rendered a positive FH interaction parameter, a crystalline solubility of approximately 0.012% w/w and an amorphous drug-polymer miscibility of approximately 7.07% w/w.
  
  
  CONCLUSIONS
  The solid dispersions are significantly supersaturated with respect to both crystalline solubility and amorphous miscibility demonstrating the influence of manufacturing methodology.
authors.affiliation: Laboratorium voor Farmacotechnologie en Biofarmacie, K.U.Leuven, Herestraat 49, bus 921, 3000, Leuven, Belgium.
authors.forename: Sandrien
authors.initials: S
authors.lastname: Janssens
authors.forename: Ann
authors.initials: A
authors.lastname: De Zeure
authors.forename: Amrit
authors.initials: A
authors.lastname: Paudel
authors.forename: Jan
authors.initials: J
authors.lastname: Van Humbeeck
authors.forename: Patrick
authors.initials: P
authors.lastname: Rombaut
authors.forename: Guy
authors.initials: G
authors.lastname: Van den Mooter
mesh_terms: D000179:Acrylates; D000465:Algorithms; D000935:Antifungal Agents / Q000008:administration & dosage / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D003890:Desiccation; D005079:Excipients; D017964:Itraconazole / Q000008:administration & dosage / Q000737:chemistry*; D011108:Polymers; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D013818:Thermogravimetry; D014961:X-Ray Diffraction
chemical_list: D000179:Acrylates; D000935:Antifungal Agents; C477020:Eudragit E100; D005079:Excipients; D011108:Polymers; D017964:Itraconazole