title: Combination of (M)DSC and surface analysis to study the phase behaviour and drug distribution of ternary solid dispersions.
abstract: OBJECTIVE
  Miscibility of the different compounds that make up a solid dispersion based formulation play a crucial role in the drug release profile and physical stability of the solid dispersion as it defines the phase behaviour of the dispersion. The standard technique to obtain information on phase behaviour of a sample is (modulated) differential scanning calorimetry ((M)DSC). However, for ternary mixtures (M)DSC alone is not sufficient to characterize their phase behaviour and to gain insight into the distribution of the active pharmaceutical ingredient (API) in a two-phased polymeric matrix.
  
  
  METHODS
  MDSC was combined with complementary surface analysis techniques, specifically time-of-flight secondary ion mass spectrometry (ToF-SIMS) and atomic force microscopy (AFM). Three spray-dried model formulations with varying API/PLGA/PVP ratios were analyzed.
  
  
  RESULTS
  MDSC, TOF-SIMS and AFM provided insights into differences in drug distribution via the observed surface coverage for 3 differently composed ternary solid dispersions.
  
  
  CONCLUSIONS
  Combining MDSC and surface analysis rendered additional insights in the composition of mixed phases in complex systems, like ternary solid dispersions.
authors.affiliation: Drug Delivery and Disposition, KU Leuven, Department of Pharmaceutical and Pharmacological Sciences, Campus Gasthuisberg ON2, Herestraat 49 b921, 3000, Leuven, Belgium.
authors.forename: Joke
authors.initials: J
authors.lastname: Meeus
authors.forename: David J
authors.initials: DJ
authors.lastname: Scurr
authors.forename: Xinyong
authors.initials: X
authors.lastname: Chen
authors.forename: Katie
authors.initials: K
authors.lastname: Amssoms
authors.forename: Martyn C
authors.initials: MC
authors.lastname: Davies
authors.forename: Clive J
authors.initials: CJ
authors.lastname: Roberts
authors.forename: Guy
authors.initials: G
authors.lastname: Van den Mooter
mesh_terms: D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D004337:Drug Carriers / Q000737:chemistry*; D017320:HIV Protease Inhibitors / Q000737:chemistry*; D019344:Lactic Acid / Q000737:chemistry*; D018625:Microscopy, Atomic Force; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D015394:Molecular Structure; D044367:Phase Transition; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D012995:Solubility; D018629:Spectrometry, Mass, Secondary Ion; D013499:Surface Properties; D044366:Transition Temperature
chemical_list: D004337:Drug Carriers; D017320:HIV Protease Inhibitors; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid