A thermal analysis method to predict the complete phase diagram of drug-polymer solid dispersions.

The aim of this work was to develop a method which uses experimentally obtainable data to predict the complete phase diagram of drug-polymer solid dispersion systems, for the first time in literature. Felodipine-poly(acrylic acid) (PAA) solid dispersion was used as an example to illustrate the application of this method. Samples were prepared with different drug loading and analyzed using differential scanning calorimetry (DSC). Values of the drug-polymer interaction parameter χ(T(m)) were calculated from the drug crystal melting point depression data. Since χ is a function of temperature (χ∼1/T) according to the Flory-Huggins theory, the obtained χ-T relationship thus enabled calculation of the complete temperature-composition phase diagram of a drug-polymer solid dispersion system. In experiments, felodipine was shown to be immiscible with PAA in almost the whole range of drug content at room temperature. Two glass transition temperatures were observed, corresponding to almost pure felodipine and pure PAA, respectively, in consistent with the predicted phase behavior.