Model-based scale-up of vacuum contact drying of pharmaceutical compounds

An integrated methodology for the scale-up of vacuum contact drying with intermittent agitation is described in this work. The methodology combines a mathematical model of vacuum contact drying, based on differential transient heat and energy balances, and a small-scale experimental apparatus for model validation and parameter estimation. The validated model was used for the estimation of drying times of six different pharmaceutical compounds at the pilot and manufacturing scale over a range of drying conditions – pressure 15–200 mbar, temperature 45–70 °C, solvents: acetone, water, methanol, n-propanol, and isopropyl acetate. The mean difference between predicted and actual drying times for the six compounds was less than 9%, which is considered a significant improvement over current semi-empirical approaches to vacuum contact drying scale-up.

► We designed a methodology for the scale-up of vacuum contact drying. ► The mathematical model includes differential mass and energy balance. ► The model has been validated across scales with six pharmaceutical compounds. ► The average accuracy of the predicted drying time was 9%.