A novel thermodynamic strategy for predicting influence of relative
humidity on stability of amorphous solid dispersions
Abstract
In this work, the influence of polymeric excipients and relative
humidity (RH) on stability of amorphous solid dispersions (ASDs) was
investigated. Irbesartan and oxaprozin of BCS Ⅱ were selected as model
active pharmaceutical ingredients (APIs). PVP and PVP/VA were chosen as
model excipients. The water sorption and the physical stability of
amorphous solid dispersions stored at constant temperature and humidity
were measured. The thermodynamic phase diagrams were constructed using
Perturbed-Chain Statistical Associating Fluid Theory (PC-SAFT) and
Gordon-Taylor equation. The results showed that the hygroscopicity of
PVP-containing was stronger than PVP/VA-containing. The water sorption
was found to significantly decrease the API solubility in the polymer as
well as the glass-transition temperature of the formulation. The
solubility of irbesartan and oxaprozin in PVP and PVP/VA were further
predicted at 25 °C with PC-SAFT. It could guide the design of amorphous
solid dispersions and selection of storage conditions.