title: Prediction of poly(ethylene) glycol-drug eutectic compositions using an index based on the van't Hoff equation.
abstract: OBJECTIVE
  To define an index based on the van't Hoff equation that can be used as a screening tool for predicting poly(ethylene) glycol (PEG)-drug eutectic composition.
  
  
  METHODS
  Phase diagrams of PEG with ritonavir, ibuprofen, fenofibrate. naproxen, and griseofulvin were constructed using differential scanning calorimetry, hot stage microscopy and powder X-ray diftractometry. Previously reported phase diagrams were also used to test the predictive capability of the index.
  
  
  RESULTS
  This work shows that a modified van't Hoff equation can be used to model the drug liquidus line of these phase diagrams. The slope of the liquidus line depends on the melting point (T(f)d) and heat of fusion (deltaH(f)d) of the drug and describes the initial rate at which the eutectic or monotectic point is approached. Based on this finding, a dimensionless index Ic was defined. The index can be calculated from the melting points of the pure components and heat of fusion of the drug. In addition to the compounds listed above, the index was found to predict the eutectic composition for flurbiprofen, temazepam and indomethacin. These compounds range over 150 degrees C in T(f)d, and from 25-65 kJ/mole in deltaH(f)d.
  
  
  CONCLUSIONS
  Using Ic the approximate eutectic composition for eight different compounds was predicted. The index provides a useful screening tool for assessing the maximum drug loading in a drug-polymer eutectic/monotectic formulation.
authors.affiliation: Global Pharmaceutical Research and Development Division, Abbott Laboratories, Abbott Park, Illinois 60064, USA. devalina.law@abbott.com
authors.forename: Devalina
authors.initials: D
authors.lastname: Law
authors.forename: Weili
authors.initials: W
authors.lastname: Wang
authors.forename: Eric A
authors.initials: EA
authors.lastname: Schmitt
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Long
mesh_terms: D005544:Forecasting / Q000379:methods*; D008956:Models, Chemical; D011092:Polyethylene Glycols / Q000737:chemistry*
chemical_list: D011092:Polyethylene Glycols