title: Evaluating scale-up rules of a high-shear wet granulation process.
abstract: This work aimed to evaluate the commonly used scale-up rules for high-shear wet granulation process using a microcrystalline cellulose-lactose-based low drug loading formulation. Granule properties such as particle size, porosity, flow, and tabletability, and tablet dissolution were compared across scales using scale-up rules based on different impeller speed calculations or extended wet massing time. Constant tip speed rule was observed to produce slightly less granulated material at the larger scales. Longer wet massing time can be used to compensate for the lower shear experienced by the granules at the larger scales. Constant Froude number and constant empirical stress rules yielded granules that were more comparable across different scales in terms of compaction performance and tablet dissolution. Granule porosity was shown to correlate well with blend tabletability and tablet dissolution, indicating the importance of monitoring granule densification (porosity) during scale-up. It was shown that different routes can be chosen during scale-up to achieve comparable granule growth and densification by altering one of the three parameters: water amount, impeller speed, and wet massing time.
authors.affiliation: Drug Product Science and Technology, Bristol-Myers Squibb, New Brunswick, New Jersey, 08901.
authors.forename: Jing
authors.initials: J
authors.lastname: Tao
authors.affiliation: Drug Product Science and Technology, Bristol-Myers Squibb, New Brunswick, New Jersey, 08901.
authors.forename: Preetanshu
authors.initials: P
authors.lastname: Pandey
authors.affiliation: Drug Product Science and Technology, Bristol-Myers Squibb, New Brunswick, New Jersey, 08901.
authors.forename: Dilbir S
authors.initials: DS
authors.lastname: Bindra
authors.affiliation: Drug Product Science and Technology, Bristol-Myers Squibb, New Brunswick, New Jersey, 08901.
authors.forename: Julia Z
authors.initials: JZ
authors.lastname: Gao
authors.affiliation: Drug Product Science and Technology, Bristol-Myers Squibb, New Brunswick, New Jersey, 08901.
authors.forename: Ajit S
authors.initials: AS
authors.lastname: Narang
mesh_terms: D002482:Cellulose / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D007785:Lactose / Q000737:chemistry; D016062:Porosity; D013607:Tablets / Q000737:chemistry*; D013678:Technology, Pharmaceutical / Q000379:methods*; D014867:Water / Q000737:chemistry*
chemical_list: D013607:Tablets; D014867:Water; D002482:Cellulose; D007785:Lactose; C109691:microcrystalline cellulose
keywords: compression; dissolution rate; granulation; porosity; processing