title: Development of a spray congealing process for the preparation of insulin-loaded lipid microparticles and characterization thereof.
abstract: A spray congealing process for the preparation of protein-loaded microparticles was developed. The influence of the process parameters atomization pressure and spraying temperature on particle size and process yield was investigated by experimental design. The employed spray congealing technique enabled the production of microparticles with yields ranging from 79% to 95% and median particle sizes (d(0.5)) from 182.2 to 315 microm. Insulin lipid microparticles could be prepared without any loss of insulin during the preparation process and the protein stability was not affected by the spray congealing process as investigated by HPLC-MS analysis. The stability of insulin encapsulated in lipid microparticles under release conditions over 28 days was assessed by investigating the residual insulin content. Starting after 3 days of release, a continuous increase of desamidoinsulin in the remaining particles of up to 7.5% after 28 days was observed. An additional degradation product was detected by HPLC and HPLC-MS analysis and identified as a covalent insulin dimer by MALDI-ToF. The microparticles did not show a burst release and testing the insulin lipid microparticles in a fibrin gel chondrocyte culture revealed that the released insulin was bioactive and had a significant effect on chondrocyte extracellular matrix production.
authors.affiliation: Department of Pharmaceutical Technology, University of Regensburg, 93040 Regensburg, Germany.
authors.forename: Angelika
authors.initials: A
authors.lastname: Maschke
authors.forename: Christian
authors.initials: C
authors.lastname: Becker
authors.forename: Daniela
authors.initials: D
authors.lastname: Eyrich
authors.forename: Josef
authors.initials: J
authors.lastname: Kiermaier
authors.forename: Torsten
authors.initials: T
authors.lastname: Blunk
authors.forename: Achim
authors.initials: A
authors.lastname: Göpferich
mesh_terms: D002356:Cartilage / Q000187:drug effects / Q000254:growth & development; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects; D004339:Drug Compounding; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000737:chemistry*; D007328:Insulin / Q000008:administration & dosage* / Q000737:chemistry*; D008055:Lipids; D008863:Microspheres; D010316:Particle Size; D013696:Temperature; D014280:Triglycerides; D014783:Viscosity
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D008055:Lipids; D014280:Triglycerides; C005859:tripalmitin