title: The effect of the physical states of binders on high-shear wet granulation and granule properties: a mechanistic approach towards understanding high-shear wet granulation process. Part I. Physical characterization of binders.
abstract: In this study, the objective is to investigate the effect of the physical state of a binder on wet granulation and granule properties using a binary model system (CaCO(3)-binder), which is essential for understanding the mechanism of wet granulation when binder is added in a dry state. Part I focus on studying the phase behavior or the physical state change of four binders: PVP K12, K29/32, HPC, and HPMC, after exposure to either moisture or liquid water. Their interaction with water was studied by measuring the water sorption of binders and the binary blends of CaCO(3)-binder. Changes in the physical states of the binders at room temperature as a function of water content was monitored via dialysis experiments, and characterized by determining the glass transition temperatures (T(g)) of the binders with water. The results suggest that the PVP binders can absorb more water than the cellulosic binders which is same for binder alone and in the binary blends. PVP K12 undergoes a phase transition from the glassy state to the rubbery/solution state at much lower water content than PVP K29/32 (10% vs. 20%) at room temperature. The phase transition for HPC occurs with 10-15% water based on rheological measurements.
authors.affiliation: Biopharmaceutics R&D, Bristol-Myers Squibb Company, 1 Squibb Drive, P.O. Box 191, New Brunswick, New Jersey 08903-0191, USA. jinjiang.li@bms.com
authors.forename: Jinjiang
authors.initials: J
authors.lastname: Li
authors.forename: Li
authors.initials: L
authors.lastname: Tao
authors.forename: Mandar
authors.initials: M
authors.lastname: Dali
authors.forename: David
authors.initials: D
authors.lastname: Buckley
authors.forename: Julia
authors.initials: J
authors.lastname: Gao
authors.forename: Mario
authors.initials: M
authors.lastname: Hubert
mesh_terms: D002119:Calcium Carbonate / Q000737:chemistry; D002482:Cellulose / Q000031:analogs & derivatives / Q000737:chemistry; D055598:Chemical Phenomena; D003956:Dialysis; D005079:Excipients / Q000737:chemistry*; D065347:Hypromellose Derivatives; D008747:Methylcellulose / Q000031:analogs & derivatives / Q000737:chemistry; D044367:Phase Transition; D011205:Povidone / Q000737:chemistry; D011208:Powders; D033081:Shear Strength; D012995:Solubility; D013678:Technology, Pharmaceutical; D044366:Transition Temperature; D014867:Water / Q000032:analysis
chemical_list: D005079:Excipients; D011208:Powders; D014867:Water; D065347:Hypromellose Derivatives; D002482:Cellulose; D008747:Methylcellulose; C008079:hydroxypropylcellulose; D011205:Povidone; D002119:Calcium Carbonate