title: Spray drying from organic solvents to prepare nanoporous/nanoparticulate microparticles of protein: excipient composites designed for oral inhalation.
abstract: OBJECTIVE
  The aim of this study was to determine if spray-drying could successfully produce microparticles containing the model protein trypsin in a form suitable for inhalation.
  
  
  METHODS
  Trypsin was spray-dried with raffinose from a methanol : n-butyl acetate solvent system (MeOH : BA). The solvent system was then adjusted to include water, and trypsin was co-spray-dried with raffinose, trehalose or hydroxpropyl-β-cyclodextrin. The spray-dried products were characterised by SEM, XRD, DSC, TGA and FTIR. Protein biological activity and in-vitro deposition of trypsin : excipient nanoporous/nanoparticulate microparticles (NPMPs) was also assessed.
  
  
  RESULTS
  The inclusion of water in a MeOH : BA solvent system allowed for the successful production of NPMPs of trypsin : excipient by spray-drying. Trypsin formulated as trypsin : excipient NPMPs retained biological activity on processing and showed no deterioration in activity or morphological characteristics when stored with desiccant at either 4 or 25°C. Hydroxpropyl-β-cyclodextrin showed advantages over the sugars in terms of producing powders with appropriate density and with greater physical stability under high-humidity conditions. Fine particle fractions of between 41 and 45% were determined for trypsin : excipient NPMPs.
  
  
  CONCLUSIONS
  NPMPs of trypsin : excipient systems can be produced by spray-drying by adjustment of the solvent system to allow for adequate solubility of trypsin.
authors.affiliation: School of Pharmacy and Pharmaceutical Sciences, University of Dublin, Trinity College Dublin, Dublin, Ireland.
authors.forename: Orla
authors.initials: O
authors.lastname: Ní Ógáin
authors.forename: Lidia
authors.initials: L
authors.lastname: Tajber
authors.forename: Owen I
authors.initials: OI
authors.lastname: Corrigan
authors.forename: Anne Marie
authors.initials: AM
authors.lastname: Healy
mesh_terms: D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000280:Administration, Inhalation; D000284:Administration, Oral; D000336:Aerosols; D004339:Drug Compounding; D016503:Drug Delivery Systems; D004356:Drug Storage; D004795:Enzyme Stability; D005079:Excipients / Q000032:analysis / Q000737:chemistry*; D006801:Humans; D008863:Microspheres; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D011208:Powders; D011487:Protein Conformation; D012995:Solubility; D012997:Solvents / Q000737:chemistry*; D013499:Surface Properties; D014357:Trypsin / Q000008:administration & dosage / Q000032:analysis / Q000737:chemistry* / Q000378:metabolism; D014867:Water / Q000032:analysis; D047392:beta-Cyclodextrins / Q000032:analysis / Q000737:chemistry
chemical_list: D000336:Aerosols; D005079:Excipients; D011208:Powders; D012997:Solvents; D047392:beta-Cyclodextrins; D014867:Water; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D014357:Trypsin