title: Spatial characterization of hot melt extruded dispersion systems using thermal atomic force microscopy methods: the effects of processing parameters on phase separation.
abstract: OBJECTIVE
  In this study we explore the use of nano-scale localized thermal analysis (LTA) and transition temperature microcopy (TTM) as a novel combined approach to studying phase separation in HME dispersions of cyclosporine A in Eudragit EPO.
  
  
  METHODS
  Modulated temperature differential scanning calorimetry (MTDSC), attenuated total reflectance FTIR spectroscopy, nano-LTA and TTM were performed on raw materials and dispersions prepared by hot melt extrusion (HME) and spin coating. For samples prepared by HME, two mixing temperatures (110°C and 150°C) and residence times (5 and 15 min) were investigated.
  
  
  RESULTS
  Spin coated samples showed an intermediate T g for the mixed systems consistent with molecular dispersion formation. The HME samples prepared at 110°C showed evidence of inhomogeneity using MTDSC and FTIR, while those produced at 150°C h showed evidence for the formation of a single phase system using MTDSC. The nanothermal methods, however, indicated the presence of phase separated cyclosporine A at the higher preparation temperature while the TTM was able to map regions of differing penetration temperatures, indicating the presence of compositionally inhomogeneous regions in all but the high processing temperature/high residence time samples.
  
  
  CONCLUSIONS
  TTM is a potentially important new method for studying phase separation and that such separation may remain undetected or poorly understood using conventional bulk analytical techniques.
authors.affiliation: School of Pharmacy, University of East Anglia, Norwich, UK, NR4 7TJ.
authors.forename: Jonathan G
authors.initials: JG
authors.lastname: Moffat
authors.forename: Sheng
authors.initials: S
authors.lastname: Qi
authors.forename: Duncan Q M
authors.initials: DQ
authors.lastname: Craig
mesh_terms: D000935:Antifungal Agents / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D016572:Cyclosporine / Q000737:chemistry*; D018625:Microscopy, Atomic Force / Q000379:methods*; D044367:Phase Transition; D011109:Polymethacrylic Acids / Q000737:chemistry*; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D044366:Transition Temperature
chemical_list: D000935:Antifungal Agents; D011109:Polymethacrylic Acids; C038300:methylmethacrylate-methacrylic acid copolymer; D016572:Cyclosporine