Prediction of Poly(ethylene) glycol-Drug Eutectic Compositions

摘要

The goal of this work was to define an index based on the van’t Hoff equation that could be used as a screening tool for predicting poly(ethylene) glycol (PEG)-drug eutectic composition. Phase diagrams of PEG with ritonavir, ibuprofen, fenofibrate, naproxen, and griseofulvin were constructed using differential scanning calorimetry, hot stage microscopy and powder X-ray diffractometry. Previously reported phase diagrams were also used to test the predictive capability of the index. This work has shown that a modified van’t Hoff equation can model the drug liquidus line of drug-PEG phase diagrams. The slope of the liquidus line depends on the melting point (T~f_d ) and heat of fusion (△H~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. The index was found to predict the eutectic composition for the compounds listed above as well as flurbiprofen-, temazepam- and indomethacin-PEG systems reported in the literature. These compounds range over 150 oC in T~f_d , and from 25-65 kJ/mole in △H~f_d . The following table shows the relationship between Ic and the drug loading at the eutectic point