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.

The influence of temperature, stirring speed, and excipients on crystal growth kinetics of mesalazine and allopurinol was investigated through experiment and chemical potential gradient model. The results indicated that the Diffusion-Surface Reaction model (DSR (1,2)) showed good performance in modeling API crystal growth kinetics within the ARDs of 4%. Excipients played a crucial role in inhibiting crystal growth in all the systems. It can not only improve the API solubility, but also reduce the crystal growth rate. By comparing diffusion rate and surface-reaction rate constant within the DSR (1,2) model, it was found that the controlling step of mesalazine crystallization was surface-reaction. Allopurinol crystallization was dominated by both surface-reaction and diffusion. Meanwhile, the crystal growth kinetics of mesalazine and allopurinol were predicted successfully with the ARDs of 2.53% and 4.78%. This work provided a mechanistic understanding of polymer influence on the inhibition of API crystal growth.