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 of the interactions of two polymer binder solutions, hydroxypropyl methylcellulose (HPMC) and polyvinyl-pyrrolidone (PVP), with individual paracetamol drug crystals. A novel micro-force balance (MFB) has been used to measure different parameters of the crystal-tobinder interaction, including the forces exerted by axially strained liquid bridges formed between either two paracetamol crystals or between a reservoir of binder solution and a single paracetamol crystal, the paracetamol-to-binder wettability, the post rupture volume distribution and the residue deposited on each crystal. Video images of the separation sequences were obtained simultaneously for analysis of bridge geometry, contact angles, volume distribution and binder residues. It was found that the formation of liquid bridges and their ability to bond particles together depends on the amount of binder left on a crystal after contacting a reservoir of binder (for example, large binder drop). Crystals in contact with HPMC were able to retain more liquid from a binder reservoir than those contacted with PVP solutions. This behaviour is seen to be more important to the final granule strength than the liquid binding force holding particles together in the wet agglomerate.