title: Decoupling the contribution of surface energy and surface area on the cohesion of pharmaceutical powders.
abstract: OBJECTIVE
  Surface area and surface energy of pharmaceutical powders are affected by milling and may influence formulation, performance and handling. This study aims to decouple the contribution of surface area and surface energy, and to quantify each of these factors, on cohesion.
  
  
  METHODS
  Mefenamic acid was processed by cryogenic milling. Surface energy heterogeneity was determined using a Surface Energy Analyser (SEA) and cohesion measured using a uniaxial compression test. To decouple the surface area and surface energy contributions, milled mefenamic acid was "normalised" by silanisation with methyl groups, confirmed using X-ray Photoelectron Spectroscopy.
  
  
  RESULTS
  Both dispersive and acid-base surface energies were found to increase with increasing milling time. Cohesion was also found to increase with increasing milling time. Silanised mefenamic acid possessed a homogenous surface with a surface energy of 33.1 ± 1.4 mJ/m(2) , for all milled samples. The cohesion for silanised mefenamic acid was greatly reduced, and the difference in the cohesion can be attributed solely to the increase in surface area. For mefenamic acid, the contribution from surface energy and surface area on cohesion was quantified to be 57% and 43%, respectively.
  
  
  CONCLUSIONS
  Here, we report an approach for decoupling and quantifying the contribution from surface area and surface energy on powder cohesion.
authors.affiliation: Surfaces and Particle Engineering Laboratory (SPEL), Department of Chemical Engineering, Imperial College London, South Kensington Campus, London, SW7 2AZ, UK.
authors.forename: Umang V
authors.initials: UV
authors.lastname: Shah
authors.forename: Dolapo
authors.initials: D
authors.lastname: Olusanmi
authors.forename: Ajit S
authors.initials: AS
authors.lastname: Narang
authors.forename: Munir A
authors.initials: MA
authors.lastname: Hussain
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Tobyn
authors.forename: Steve J
authors.initials: SJ
authors.lastname: Hinder
authors.forename: Jerry Y Y
authors.initials: JY
authors.lastname: Heng
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry*; D003460:Crystallization; D005079:Excipients / Q000737:chemistry; D008528:Mefenamic Acid / Q000737:chemistry*; D008855:Microscopy, Electron, Scanning; D010316:Particle Size; D056951:Photoelectron Spectroscopy; D011208:Powders; D012821:Silanes / Q000737:chemistry; D013499:Surface Properties; D013678:Technology, Pharmaceutical / Q000379:methods*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D005079:Excipients; D011208:Powders; D012821:Silanes; D008528:Mefenamic Acid; C040863:dichlorodimethylsilane