Abstract
In this work, we proposed the method to maintain the desired level of drug’s solubility within the polymer matrix by adjusting conditions to uphold the same molecular dynamics of the system (e.g., temperature for set elevated pressure or vice versa). Namely, we observed, that recrystallization of the drug from the supersaturated drug–polymer system, initiated for the same structural relaxation time of the sample (τα-1) ceases when certain, different than the initial, molecular mobility of the systems is reached (τα-2)—regardless of a given combination of temperature and pressure conditions. Based on the presented results, one can conclude that the molecular dynamics seem to control the process of recrystallization of the excess amount of solute from the supersaturated solution (e.g., small molecules dissolved within the polymer). Therefore, it appears that the elevated pressure compensates the effect of solubility enhancement caused by the elevated temperature. Such information not only is of fundamental relevance in science but also, from a much broader perspective, could be potentially very useful considering extrusion-based manufacturing methods.
Highlights
Antiandrogen drug flutamide (FL) was dissolved within the copolymer matrix Kollidon VA64 (PVP/VA) and its solubility was examined at various sets of elevated temperatures and pressures.[26]
In order to test the validity of the proposed idea, we performed the series of dielectric measurements under various temperature and pressure conditions and analyzed recently published data of FL-Poly vinylpyrrolidone vinylacetate Kollidon VA64 (PVP/VA).[26]
The initial part of this study will focus on the analysis of the already published data, especially on the temperature dependencies of the relaxation times of the FL-PVP/VA systems under various pressure conditions
Summary
The solubility of small molecules (SMs) within the polymer matrixes has been of great scientific interest in the past decades.[1−6] The special case of this phenomenon considering drugs as SMs dissolved within the polymers has been extensively explored because of its importance to the pharmaceutical industry.[5,7−16] A great number of the experiments, performed under isobaric (ambient) conditions, allowed to explore the subject of drug−polymer solubility.[3,5,10,11,15,17−19] As a result of those efforts, our knowledge about this process increased. Article changes occurring in the molecular dynamics of the examined system during the whole process.[8,16,26,28,29] the value of system, the structural which reflects relaxation time its molecular m(τoαb)iliotfy,3th0−e32mecaasnurebde determined during dielectric measurements As it was proven in the case of a viscous liquid, the effect of the increasing pressure on τα is similar to the effect of the decreasing temperature.[33,34] one can directly link it to temperature (as inversely proportional to) and pressure (as proportional p.35−38 to) in the following fashion: τα. Dielectric studies of FL and its binary systems were performed immediately after its vitrification by fast cooling of the melt in a parallel-plate cell made of stainless steel (diameter 15 mm and a 0.1 mm gap with quartz spacers). The temperature was adjusted with a precision of 0.1 K by the Julabo heating circulator (Seelbach, Germany)
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