title: New insights into respirable protein powder preparation using a nano spray dryer.
abstract: In this study the Nano Spray Dryer B-90 (BÜCHI Labortechnik AG, Flawil, Switzerland) was evaluated with regard to the drying of proteins and the preparation of respirable powders in the size range of 1-5 μm. β-galactosidase was chosen as a model protein and trehalose was added as a stabilizer. The influence of inlet temperature, hole size of the spray cap membrane and ethanol concentration in the spray solution was studied using a 3³ full factorial design. The investigated responses were enzyme activity, particle size, span, yield and shelf life. Furthermore, the particle morphology was examined. The inlet temperature as well as the interaction of inlet temperature and spray cap size significantly influenced the enzyme activity. Full activity was retained with the optimized process. The particle size was affected by the hole size of the spray cap membrane and the ethanol content. The smallest cap led to a monodisperse particle size distribution and the greatest yield of particles of respirable size. Higher product recovery was achieved with lower inlet temperatures, higher ethanol contents and smaller cap sizes. Particle morphology differed depending on the cap size. The protein exhibited higher storage stability when spray dried without ethanol and when a larger spray cap size was used.
authors.affiliation: Industrial Pharmacy Laboratory, Department of Pharmaceutical Sciences, University of Basel, Mülhauserstrasse 51, 4056 Basel, Switzerland.
authors.forename: K
authors.initials: K
authors.lastname: Bürki
authors.forename: I
authors.initials: I
authors.lastname: Jeon
authors.forename: C
authors.initials: C
authors.lastname: Arpagaus
authors.forename: G
authors.initials: G
authors.lastname: Betz
mesh_terms: D000280:Administration, Inhalation; D001702:Biopharmaceutics / Q000295:instrumentation* / Q000379:methods*; D004355:Drug Stability; D004356:Drug Storage; D004867:Equipment Design; D000431:Ethanol / Q000737:chemistry; D008567:Membranes, Artificial; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D010316:Particle Size; D011208:Powders; D011506:Proteins / Q000008:administration & dosage* / Q000737:chemistry; D012107:Research Design; D013499:Surface Properties; D014199:Trehalose / Q000737:chemistry; D001616:beta-Galactosidase / Q000008:administration & dosage / Q000737:chemistry
chemical_list: D008567:Membranes, Artificial; D011208:Powders; D011506:Proteins; D000431:Ethanol; D014199:Trehalose; D001616:beta-Galactosidase