The purpose of this work was to investigate the distribution of water in a physically unstable amorphous solid dispersion (polyvinylpyrrolidone (PVP) and griseofulvin (as a model hydrophobic drug)), both as the sample absorbs water and during prolonged exposure to elevated humidity by use of dynamic vapour sorption combined with near infrared (DVS-NIR). The solid dispersion absorbed much less water than the sum of the water sorption of the individual components. This suggests that griseofulvin hindered PVP from absorbing water through the formation of the solid dispersion. Prolonged storage of the solid dispersion at 75% RH resulted in no significant mass change. Whilst this would usually be interpreted as the absence of crystallization, the NIR spectra demonstrated that crystallization occurred. The reason for the lack of a weight loss was that the expelled water from amorphous griseofulvin was sorbed by PVP, meaning that as the dispersion was broken by the crystallisation of griseofulvin, the PVP was once again free to sorb water (in line with the higher water sorption shown by PVP alone, and in contrast with the lower sorption of water by the solid dispersion). As water is a key factor in the physical stability of amorphous systems, understanding how and where water is absorbed and how this is liable to change is an important advance and offers promise in understanding the mechanism of stabilisation of solid dispersions, and therefore may be useful to predict the stability of new API dispersions.
Keywords: Amorphous; Crystallisation; Near infrared; Solid dispersion; Vapour sorption.
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