title: The effect of the physical state of binders on high-shear wet granulation and granule properties: a mechanistic approach to understand the high-shear wet granulation process. part IV. the impact of rheological state and tip-speeds.
abstract: The purpose of this study is to provide a mechanistic understanding concerning the effect of tip-speed on a granulation at various binder rheological states; the in situ rheological state of a binder was controlled by exposing a granulation blend to 96% relative humidity. This approach allowed us to investigate the impact of tip-speed on granule consolidation coupled with the in situ binder state, which was not possible using a conventional granulation approach. Experimentally, the rheological state of binders was characterized using a rheometer. Granule size and granule porosity were measured by Qicpic instrument and Mercury Intrusion Porosimetry, respectively. For the granulations containing binders at viscous state (PVP K17 and PVP K29/32), the granule size increased significantly with mixing time and the growth rate increased with tip-speed until 5.8 m/s; when binders were at viscoelastic state, tip-speed had no impact on granulation. Furthermore, the granule porosity was higher for granulation with binders at viscoelastic state (HPC and PVP K90), whereas it was lower for granulation with binders at viscous state. In addition, the impeller tip-speed had minimal impact on the porosity of the final granules. Finally, Ennis' model was used for interpreting results, providing mechanistic insights on granulation.
authors.affiliation: Drug Product Science & Technology, Bristol-Myers Squibb, New Brunswick, New Jersey, 08901.
authors.forename: Jinjiang
authors.initials: J
authors.lastname: Li
authors.forename: Li
authors.initials: L
authors.lastname: Tao
authors.forename: David
authors.initials: D
authors.lastname: Buckley
authors.forename: Jing
authors.initials: J
authors.lastname: Tao
authors.forename: Julia
authors.initials: J
authors.lastname: Gao
authors.forename: Mario
authors.initials: M
authors.lastname: Hubert
mesh_terms: D002482:Cellulose / Q000031:analogs & derivatives* / Q000737:chemistry; D004339:Drug Compounding / Q000379:methods; D005079:Excipients / Q000737:chemistry*; D006813:Humidity; D010316:Particle Size; D044367:Phase Transition; D016062:Porosity; D011205:Povidone / Q000737:chemistry*; D012212:Rheology; D014783:Viscosity
chemical_list: D005079:Excipients; D002482:Cellulose; C008079:hydroxypropylcellulose; D011205:Povidone
keywords: formulation; glass transition; granulation; kinetics; polymers; rheology; surface energy; viscosity; water sorption; wetting