Dehydration of Theophylline: Static Gravimetric Analysis and Near Infrared Spectroscopy Monitoring of Vacuum Bed Vacuum Bed Drying

Etudiant :Amira TOUIL (Université de Lyon et Université de Gabès)

Ecole doctorale :Array

Directeur ou Directrice :Roman PECZALSKI (Université de Lyon) et Fethi ZAGROUBA (Université de Carthage)

Date de la soutenance :20140303

The aim of this work was to investigate the dehydration process of a single static layer of theophylline’s crystals under different hygrothermal conditions and the dehydration-drying process of a stirred bed of theophylline in a vacuum contact dryer in nearly the same hygrothermal conditions.
First of all, the hydrated and dehydrated forms of theophylline were identified using DSC, TGA and PXRD devices. Next, the static gravimetric experiments at constant temperature and relative humidity were carried out and the water content evolutions with time were recorded at temperatures from 20 to 80°C and humidities from 4 to 50%. Then, the thermodynamic equilibrium data were reported as desorption isotherms and solid-solid phase diagrams. Finally, the dehydration kinetics were analyzed. The dehydration rate constant was found to increase exponentially with temperature and to decrease exponentially with relative humidity. A simple semi-empirical model for prediction of the product water content evolution with time for different processing parameters was developed.

In the second part of the work, it was first proven that NIRS coupled with PLS regression enabled to monitor in-line and in-situ the exact composition of the mixture of different forms of theophylline (and of water) during drying. Second, the influence of operating parameters (temperature and water activity) on the kinetics of solid state transformations was investigated. It was observed that the dehydration begun by the formation of the metastable anhydrate and, after a time delay, continued by the formation of the stable one. It was also pointed out that the temperature was the main process factor controlling not only the overall process rate but also the final contents of the stable and metastable anhydrates, this observation being valid for the considered dryer and for the considered operating conditions.