title: The use of quasi-isothermal modulated temperature differential scanning calorimetry for the characterization of slow crystallization processes in lipid-based solid self-emulsifying systems.
abstract: OBJECTIVE
  Slow or incomplete crystallization may be a significant manufacturing issue for solid lipid-based dosage forms, yet little information is available on this phenomenon. In this investigation we suggest a novel means by which slow solidification may be monitored in Gelucire 44/14 using quasi-isothermal modulated temperature DSC (QiMTDSC).
  
  
  METHODS
  Conventional linear heating and cooling DSC methods were employed, along with hot stage microscopy (HSM), for basic thermal profiling of Gelucire 44/14. QiMTDSC experiments were performed on cooling from the melt, using a range of incremental decreases in temperature and isothermal measurement periods.
  
  
  RESULTS
  DSC and HSM highlighted the main (primary) crystallization transition; solid fat content analysis and kinetic analysis were used to profile the solidification process. The heat capacity profile from QiMTDSC indicated that after an initial energetic primary crystallisation, the lipid underwent a slower period of crystallization which continued to manifest at much lower temperatures than indicated by standard DSC.
  
  
  CONCLUSIONS
  We present evidence that Gelucire 44/14 undergoes an initial crystallization followed by a secondary, slower process. QIMTDSC appears to be a promising tool in the investigation of this secondary crystallization process.
authors.affiliation: School of Pharmacy, University of East Anglia, Earlham Road, Norwich, Norfolk, NR4 7TJ, UK.
authors.forename: Sarah O
authors.initials: SO
authors.lastname: Otun
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Meehan
authors.forename: Sheng
authors.initials: S
authors.lastname: Qi
authors.forename: Duncan Q M
authors.initials: DQ
authors.lastname: Craig
mesh_terms: D002152:Calorimetry, Differential Scanning; D003460:Crystallization; D004655:Emulsions; D005079:Excipients / Q000737:chemistry*; D007700:Kinetics; D008055:Lipids / Q000737:chemistry*; D044367:Phase Transition; D011092:Polyethylene Glycols / Q000737:chemistry*; D013678:Technology, Pharmaceutical / Q000379:methods*; D044366:Transition Temperature
chemical_list: D004655:Emulsions; D005079:Excipients; D008055:Lipids; C104509:gelucire 44-14; D011092:Polyethylene Glycols