title: Raman mapping of mannitol/lysozyme particles produced via spray drying and single droplet drying.
abstract: OBJECTIVE
  This study aimed to investigate the effect of a model protein on the solid state of a commonly used bulk agent in spray-dried formulations.
  
  
  METHODS
  A series of lysozyme/mannitol formulations were spray-dried using a lab-scale spray dryer. Further, the surface temperature of drying droplet/particles was monitored using the DRYING KINETICS ANALYZER™ (DKA) with controllable drying conditions mimicking the spray-drying process to estimate the drying kinetics of the lysozyme/mannitol formulations. The mannitol polymorphism and the spatial distribution of lysozyme in the particles were examined using X-ray powder diffractometry (XRPD) and Raman microscopy. Partial Least Squares Discriminant Analysis was used for analyzing the Raman microscopy data.
  
  
  RESULTS
  XRPD results indicated that a mixture of β-mannitol and α-mannitol was produced in the spray-drying process which was supported by the Raman analysis, whereas Raman analysis indicated that a mixture of α-mannitol and δ-mannitol was detected in the single particles from DKA. In addition Raman mapping indicated that the presence of lysozyme seemed to favor the appearance of α-mannitol in the particles from DKA evidenced by close proximity of lysozyme and mannitol in the particles.
  
  
  CONCLUSIONS
  It suggested that the presence of lysozyme tend to induce metastable solid state forms upon the drying process.
authors.affiliation: Department of Pharmacy, University of Copenhagen, Universitetsparken 2, 2100, Copenhagen, Denmark.
authors.forename: Jari Pekka
authors.initials: JP
authors.lastname: Pajander
authors.forename: Sanni
authors.initials: S
authors.lastname: Matero
authors.forename: Jakob
authors.initials: J
authors.lastname: Sloth
authors.forename: Feng
authors.initials: F
authors.lastname: Wan
authors.forename: Jukka
authors.initials: J
authors.lastname: Rantanen
authors.forename: Mingshi
authors.initials: M
authors.lastname: Yang
mesh_terms: D000336:Aerosols; D002626:Chemistry, Pharmaceutical; D018360:Crystallography, X-Ray; D003890:Desiccation; D016002:Discriminant Analysis; D004795:Enzyme Stability; D005079:Excipients / Q000737:chemistry*; D007700:Kinetics; D016018:Least-Squares Analysis; D008353:Mannitol / Q000737:chemistry*; D009113:Muramidase / Q000737:chemistry*; D010316:Particle Size; D033362:Powder Diffraction; D011208:Powders; D013059:Spectrum Analysis, Raman; D013678:Technology, Pharmaceutical / Q000379:methods*; D013696:Temperature
chemical_list: D000336:Aerosols; D005079:Excipients; D011208:Powders; D008353:Mannitol; D009113:Muramidase