METHOD FOR EVALUATING THE SOLUBILITY OF A CRYSTALLINE SUBSTANCE IN A POLYMER

1 . A method for evaluating the solubility of a crystalline substance in a polymer, comprising

a) providing at least one sample of an intimate crystalline substance/polymer mixture at a predetermined crystalline substance concentration;

b) annealing the sample at a constant temperature T a for a period of time;

c) heating the annealed sample while recording the heat flux over time by DSC;

d) identifying a DSC dissolution endotherm in the recorded heat flux, if any;

e) considering the crystalline substance concentration as a concentration above the crystalline substance solubility in the polymer at temperature T a when there is a DSC dissolution endotherm identified, and considering the crystalline substance concentration as a concentration less than or equal to the crystalline substance solubility in the polymer at temperature T a when there is no DSC dissolution endotherm identified.

2 . The method of claim 1 , wherein the period of time for annealing the sample is at least 60 min.

3 . The method of claim 1 , which comprises (a) providing a plurality of samples at different crystalline substance concentrations.

4 . The method of claim 1 , which comprises (a) providing a plurality of samples at the same crystalline substance concentration and (b) annealing the samples at different temperatures T a .

5 . The method of claim 1 , wherein, when there is a DSC dissolution endotherm identified, steps (a) to (e) are repeated at a lower crystalline substance concentration or at a higher temperature T a .

6 . The method of claim 1 , wherein, when there is no DSC dissolution endotherm identified, steps (a) to (e) are repeated at a higher crystalline substance concentration or at a lower temperature T a .

7 . The method of claim 1 , comprising recording the heat flux over time by DSC at a heating rate in the range of 5° C./min to 15° C./min.

8 . The method of claim 1 , wherein the intimate mixture is obtained by joint cryomilling of the crystalline substance and the polymer.

9 . The method of any one of claim 1 , wherein the crystalline substance is a pharmaceutically active ingredient.

10 . A method for evaluating the solubility of a crystalline substance in a polymer at the glass transition temperature Tg, comprising

a) establishing the solubility of the crystalline substance in the polymer as a function of temperature by the method of claim 1 ,

b) providing a plurality of crystalline substance/polymer mixtures having different crystalline substance concentrations and determining Tg of a liquid formed by melting each of the mixtures,

b) plotting Tg over the crystalline substance concentrations of the mixtures,

c) determining the solubility at Tg as the intersection of the solubility temperature plot and the Tg plot.

11 . The method of claim 10 , wherein Tg is determined by a DSC method.