1 research outputs found
Molecular Dynamics, Recrystallization Behavior, and Water Solubility of the Amorphous Anticancer Agent Bicalutamide and Its Polyvinylpyrrolidone Mixtures
In this paper, we investigated the
molecular mobility and physical
stability of amorphous bicalutamide, a poorly water-soluble drug widely
used in prostate cancer treatment. Our broadband dielectric spectroscopy
measurements and differential scanning calorimetry studies revealed
that amorphous BIC is a moderately fragile material with a strong
tendency to recrystallize from the amorphous state. However, mixing
the drug with polymer polyvinylpyrrolidone results in a substantial
improvement of physical stability attributed to the antiplasticizing
effect governed by the polymer additive. Furthermore, IR study demonstrated
the existence of specific interactions between the drug and excipient.
We found out that preparation of bicalutamide–polyvinylpyrrolidone
mixture in a 2–1 weight ratio completely hinder material recrystallization.
Moreover, we determined the time-scale of structural relaxation in
the glassy state for investigated materials. Because molecular mobility
is considered an important factor governing crystallization behavior,
such information was used to approximate the long-term physical stability
of an amorphous drug and drug–polymer systems upon their storage
at room temperature. Moreover, we found that such systems have distinctly
higher water solubility and dissolution rate in comparison to the
pure amorphous form, indicating the genuine formulation potential
of the proposed approach