title: Probing the effects of experimental conditions on the character of drug-polymer phase diagrams constructed using Flory-Huggins theory.
abstract: OBJECTIVE
  Amorphous drug-polymer solid dispersions have been found to result in improved drug dissolution rates when compared to their crystalline counterparts. However, when the drug exists in the amorphous form it will possess a higher Gibb's free energy than its associated crystalline state and can recrystallize. Drug-polymer phase diagrams constructed through the application of the Flory Huggins (F-H) theory contain a wealth of information regarding thermodynamic and kinetic stability of the amorphous drug-polymer system. This study was aimed to evaluate the effects of various experimental conditions on the solubility and miscibility detections of drug-polymer binary system.
  
  
  METHODS
  Felodipine (FD)-Polyvinylpyrrolidone (PVP) K15 (PVPK15) and FD-Polyvinylpyrrolidone/vinyl acetate (PVP/VA64) were the selected systems for this research. Physical mixtures with different drug loadings were mixed and ball milled. These samples were then processed using Differential Scanning Calorimetry (DSC) and measurements of melting point (Tend) and glass transition (Tg) were detected using heating rates of 0.5, 1.0 and 5.0°C/min.
  
  
  RESULTS
  The melting point depression data was then used to calculate the F-H interaction parameter (χ) and extrapolated to lower temperatures to complete the liquid-solid transition curves. The theoretical binodal and spinodal curves were also constructed which were used to identify regions within the phase diagram. The effects of polymer selection, DSC heating rate, time above parent polymer Tg and polymer molecular weight were investigated by identifying amorphous drug miscibility limits at pharmaceutically relevant temperatures.
  
  
  CONCLUSIONS
  The potential implications of these findings when applied to a non-ambient processing method such as Hot Melt Extrusion (HME) are also discussed.
authors: The Drug Delivery and Biomaterials Group, School of Pharmacy Medical Biology Centre, Queen's University, 97 Lisburn Road, BT9 7BL, Belfast, Northern Ireland, UK.
authors: Conor
authors: C
authors: Donnelly
authors: Yiwei
authors: Y
authors: Tian
authors: Catherine
authors: C
authors: Potter
authors: David S
authors: DS
authors: Jones
authors: Gavin P
authors: GP
authors: Andrews
mesh_terms: D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D003460:Crystallization; D004355:Drug Stability; D015736:Felodipine / Q000737:chemistry*; D007700:Kinetics; D008970:Molecular Weight; D044367:Phase Transition; D011759:Pyrrolidines / Q000737:chemistry*; D013816:Thermodynamics; D044366:Transition Temperature; D014753:Vinyl Compounds / Q000737:chemistry*
chemical_list: D011759:Pyrrolidines; D014753:Vinyl Compounds; C402301:poly(vinylpyrrolidone-co-vinyl-acetate); D015736:Felodipine