title: Introduction of a new scaling approach for particle size reduction in toothed rotor-stator wet mills.
abstract: A new scaling approach has been demonstrated for particle size reduction of an active pharmaceutical ingredient (API) in toothed rotor-stator wet mills for a wide range of wet milling conditions and scales. Compound A was crystallized by a cooling crystallization protocol in ethanol and wet milled with 2 types of lab scale mills and 1 pilot plant mill. The particle size was analyzed by FBRM (focused beam reflectance measurement), static light scattering and optical microscopy. The correlation between particle size and the energy input calculations, tailored for the toothed rotor-stator wet mill, had R(2)=0.90 on a logarithmic plot. The new scaling approach forms the basis to correlate API particle size to energy input in toothed rotor-stator wet mills by accounting for wet mill tooth configuration and geometry, rotor tip speed and the probabilistic effects of collision such as shear frequency and slurry residence time.
authors.affiliation: Drug Product Science & Technology, Bristol-Myers Squibb, Co., New Brunswick, NJ 08903, USA. Electronic address: joshua.engstrom@bms.com.
authors.forename: Joshua
authors.initials: J
authors.lastname: Engstrom
authors.forename: Chenchi
authors.initials: C
authors.lastname: Wang
authors.forename: Chiajen
authors.initials: C
authors.lastname: Lai
authors.forename: Jason
authors.initials: J
authors.lastname: Sweeney
mesh_terms: D003460:Crystallization / Q000295:instrumentation / Q000379:methods; D004339:Drug Compounding / Q000295:instrumentation / Q000379:methods; D010316:Particle Size; D013678:Technology, Pharmaceutical / Q000295:instrumentation / Q000379:methods*
keywords: Comminution; Shear frequency; Tip speed; Wet milling