Prédiction des interactions substrat/liant lors de la granulation (étude expérimentale dans un mélangeur à fort taux de cisaillement, approches thermodynamiques par simulation moléculaire)

This study deals with the batch wet granulation of pharmaceutical products with binder solution in high shear mixer. This work aims to develop a predictivemethodology and investigation tolls to choose the thermodynamic parameters and the process variables in order to ensure the quality of granules properties produced. Hence, we studied the effect of process variables, products thermodynamics variables and solid solubility. The characterisation of the surface free energy and the wetting of the powder are performed using the contact angle. The molecular simulation is used to calculate the solubility or the cohesions parameters. It is found that the agglomeration depend on adimensional number Caw which characterises the ratio between the friction forces to the work of adhesion. For Caw lower than 1, the dominant forces in the granulation process are the capillary and/or interfacial forces. Also, increasing the work of adhesion enhances the growth kinetics. The viscous forces predominate when the Caw becomes higher than 1.65, and the granule growth is controlled by the dissipation of the viscous forces. Moreover, the results of our study show that the solubility parameters and the surface free energy approaches can be used for the selection of a suitable binder in high shear mixer granulation.TOULOUSE-ENSIACET (315552325) / SudocSudocFranceF