title: The effect of the physical states of binders on high-shear wet granulation and granule properties: a mechanistic approach toward understanding high-shear wet granulation process. Part II. Granulation and granule properties.
abstract: The objective is to provide mechanistic understanding of a preferred wet granulation process that a binder is added in a dry state. Blends of CaCO(3) and binders were prepared and used as model systems, and they were exposed to either 96% RH (rubbery/solution state) or 60% RH (glassy state) at room temperature to control the physical state of the binders, followed by high-shear granulation and particle size measurement. The blends of PVP K12, PVP K29/32, and HPC showed a significant increase in particle size after exposure to 96% RH. An increase of aspect ratio was also observed for the blend of HPC. In contrast, the blends being exposed to 60% RH did not exhibit any increase in particle size or aspect ratio. Regarding the effect of binder molecular weight on the mechanical strength of granules, granules of PVP K29/32 had higher strength than granules of PVP K12. This can be explained using polymer entanglement theory, in which the degree of polymerization (DP) of (N ∼ 440-540) of PVP K29/32 is above the critical value (N(c)  ∼ 300-600) for entanglement; while DP of PVP K12 (N ∼ 20-30) is below it. Finally, a water sorption-phase transition-diffusion induced granule growth model for granulation has been suggested.
authors.affiliation: Biopharmaceutics R&D, Bristol-Myers Squibb Company, 1 Squibb Drive, PO 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; D004058:Diffusion; D005079:Excipients / Q000737:chemistry*; D065347:Hypromellose Derivatives; D008747:Methylcellulose / Q000031:analogs & derivatives / Q000737:chemistry; D008956:Models, Chemical; D010316:Particle Size; D044367:Phase Transition; D011205:Povidone / Q000737:chemistry; D011208:Powders; D033081:Shear Strength; D012995:Solubility; D013678:Technology, Pharmaceutical; 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