title: Effect of milling on particle shape and surface energy heterogeneity of needle-shaped crystals.
abstract: OBJECTIVE
  Milling and micronization of particles are routinely employed in the pharmaceutical industry to obtain small particles with desired particle size characteristics. The aim of this study is to demonstrate that particle shape is an important factor affecting the fracture mechanism in milling.
  
  
  METHODS
  Needle-shaped crystals of the β polymorph of D-mannitol were prepared from recrystallization in water. A portion of the recrystallized materials was ball-milled. Unmilled and milled sieved fractions of recrystallized D-mannitol were analyzed by dynamic image analysis (DIA) and inverse gas chromatography (IGC) at finite concentration to explain the breakage/fracture behavior.
  
  
  RESULTS
  In the process of ball-milling, D-mannitol preferentially fractured along their shortest axis, exposing (011) plane with increased hydrophilicity and increased bounding rectangular aspect ratio. This is in contrary to attachment energy modeling which predicts a fracture mechanism across the (010) plane with increased hydrophobicity, and small change in particle shape.
  
  
  CONCLUSIONS
  Crystal size, and more importantly, crystal shape and facet-specific mechanical properties, can dictate the fracture/cleavage behavior of organic crystalline materials. Thorough understanding of the crystal slip systems, combining attachment energy prediction with particle shape and surface characterization using DIA and IGC, are important in understanding fracture behavior of organic crystalline solids in milling and micronization.
authors.affiliation: Global Pharmaceutical Research & Development, Abbott Laboratories, 1401 Sheridan Road, North Chicago, Illinois, 60064, USA. raimundo.ho@abbott.com
authors.forename: Raimundo
authors.initials: R
authors.lastname: Ho
authors.forename: Majid
authors.initials: M
authors.lastname: Naderi
authors.forename: Jerry Y Y
authors.initials: JY
authors.lastname: Heng
authors.forename: Daryl R
authors.initials: DR
authors.lastname: Williams
authors.forename: Frank
authors.initials: F
authors.lastname: Thielmann
authors.forename: Peter
authors.initials: P
authors.lastname: Bouza
authors.forename: Adam R
authors.initials: AR
authors.lastname: Keith
authors.forename: Greg
authors.initials: G
authors.lastname: Thiele
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Burnett
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods*; D002849:Chromatography, Gas / Q000379:methods; D003460:Crystallization / Q000379:methods; D057927:Hydrophobic and Hydrophilic Interactions; D008353:Mannitol / Q000737:chemistry; D010316:Particle Size; D013499:Surface Properties; D013678:Technology, Pharmaceutical / Q000379:methods*; D014867:Water / Q000737:chemistry
chemical_list: D014867:Water; D008353:Mannitol