Predicting the performance of granulation binders through micro-mechanistic observations

The selection of an appropriate polymeric binder to be used to agglomerate drug with excipients is a critical issue for the development of high shear wet granulation processes for pharmaceutical tablet systems. The aim of the study reported here is to determine the potential for successful granulation through measurement and prediction of the interactions of the polymer solutions with individual drug particles. A novel micro-force balance (MFB) has been used to measure the forces exerted by axially strained liquid bridges of hydroxypropyl methylcellulose (HPMC) and polyvinylpyrrolidone (PVP) formed between either two paracetamol crystals or between a micro-pipette and a single paracetamol crystal. Video images were obtained simultaneously of the separation sequences for analysis of bridge geometry and contact angles. It was found that the formation of liquid bridges and their ability to bond the particles together depends on the wetting behaviour of the liquid on the particles. Binders that dewet the solid surfaces during separation are shown to produce weaker adhesion forces.