title: Identifying and mapping surface amorphous domains.
abstract: OBJECTIVE
  Undesirable amorphous material generation during formulation is implicated in a growing number of pharmaceutical problems. Due to the importance of interfacial properties in many drug delivery systems, it seems that surface amorphous material is particularly significant. Consequently, this study investigates a range of methods capable of detecting and mapping surface amorphous material.
  
  
  METHODS
  A micron-sized localized surface domain of amorphous sorbitol is generated using a novel localized heating method. The domain is subsequently investigated using atomic force microscopy (AFM) imaging, nanomechanical measurements, and Raman microscopy 3-D profiling.
  
  
  RESULTS
  AFM phase and height images reveal nanoscale-order variations within both crystalline and amorphous sorbitol domains. Nanomechanical measurements are able to quantitatively distinguish the amorphous and crystalline domains through local Young's modulus measurements. Raman microscopy also distinguishes the amorphous and crystalline sorbitol through variations in peak width. This is shown to allow mapping of the 3-D distribution of the amorphous phase and is hence complementary to the more surface sensitive AFM measurements.
  
  
  CONCLUSIONS
  AFM and Raman microscopy map the distribution of amorphous material at the surface of a sorbitol crystal with submicron spatial resolution, demonstrating surface analysis methods for characterizing semicrystalline solids generated during pharmaceutical processing.
authors: Molecular Profiles Ltd., 8 Orchard Place, Nottingham Business Park, Nottingham, NG8 6PX, UK.
authors: Stuart
authors: S
authors: Ward
authors: Mark
authors: M
authors: Perkins
authors: Jianxin
authors: J
authors: Zhang
authors: Clive J
authors: CJ
authors: Roberts
authors: Claire E
authors: CE
authors: Madden
authors: Shen Y
authors: SY
authors: Luk
authors: Nikin
authors: N
authors: Patel
authors: Stephen J
authors: SJ
authors: Ebbens
mesh_terms: D002626:Chemistry, Pharmaceutical; D005079:Excipients / Q000737:chemistry*; D018625:Microscopy, Atomic Force; D008855:Microscopy, Electron, Scanning; D013012:Sorbitol / Q000737:chemistry*; D013059:Spectrum Analysis, Raman; D013499:Surface Properties
chemical_list: D005079:Excipients; D013012:Sorbitol