Influence mechanism of excipients on drug crystallization: experimental
investigation and model analysis and prediction
Abstract
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.