Comparative impact of different binder addition methods, binders and diluents on resulting granule and tablet attributes via high shear wet granulation

This study investigated comparative impact of different binder addition methods (pouring, dripping, spraying), binders and diluents on resulting granule and tablet attributes via high shear wet granulation. Lactose monohydrate and mannitol as diluents, and hydroxypropyl methylcellulose (HPMC E5) and polyvinylpyrrolidone (PVP K30) as binders were used. Granules were characterized for morphology, bulk-density, tapped-density, flow, size, segregation-potential and friability. To determine granule friability, procedure described in European Pharmacopoeia was slightly modified to reduce manual-variations and obtain appreciable discrimination between the formulations. Binder-diluent affinity was assessed by measuring contact angles of diluent-dispersion droplets on binder films over a period of time. All blends were pressed at the same compression force and resulting tablets were characterized for pharmacotechnical properties. Results revealed that the binder addition methods altered granule-shape, which predominantly governed the granule flow. The binder addition by spraying increased fines, blend segregation-potential, granule friability, tablet tensile-strength and tablet disintegration-time; binder addition by pouring showed an opposite impact. Mannitol granules exhibited lower bulk density, superior flow, lower segregation-potential and higher friability than their lactose counterparts. Amongst binders, PVP produced more friable granules compared to HPMC. The high polydispersity-index of polymer-binder induced non-homogeneity facilitating the blend segregation-potential. Due to higher affinity, HPMC was suitable binder for mannitol, and PVP for lactose to promote granule growth. The binder-diluent affinity dominated viscosity and surface tension of binder solution to improve granule size. Increase in granule size decreased granule-friability, which subsequently decreased tablet hardness, tensile-strength and disintegration-time. Mannitol produced harder tablets, and lactose tablets disintegrated faster by all binders and binder addition methods. [Display omitted] •Binder addition methods alter granule shape that predominantly governs granule flow.•Binder-diluent affinity dominates other factors to influence the granule growth.•PVP as a binder produce more round and friable granules compared to the HPMC.•High polydispersity index of polymer-binder facilitates blend segregation potential.•Mannitol tablets achieve higher hardness, while lactose tablets dintegr