How does the high pressure affects the solubility of the drug within the polymer matrix in solid dispersion systems

In this paper, we employed Broadband Dielectric Spectroscopy (BDS) in order to determine the effect of the high pressure on the solubility limits of the amorphous flutamide within Kollidon VA64 matrix. In order to achieve this goal, drug-polymer systems have been examined: (i) at ambient pressure and both isothermal and nonisothermal conditions by means of BDS as well as Differential Scanning Calorimetry (DSC), to validate proposed method; (ii) at high pressure conditions (20 and 50 MPa) and elevated temperatures (343 K, 353 K and 363 K) by means of dielectric spectroscopy. Our studies revealed that regardless of applied pressure the solubility of the flutamide within the co-polymer matrix increases with increasing temperature at isobar conditions. Moreover, our results clearly indicate that with increasing pressure the solubility of the drug within the polymer matrix is decreasing at isothermal conditions. Therefore, during the solubility limit studies one should consider the situation in which by increasing the pressure (at constant temperature) would achieve an effect similar to the lowering of the temperature (at constant pressure).