title: Toward intradermal vaccination: preparation of powder formulations by collapse freeze-drying.
abstract: Intradermal powder immunization is an emerging technique in vaccine delivery. The purpose of this study was to generate powder particles for intradermal injection by freeze-drying and subsequent cryo-milling. Two different freeze-drying protocols were compared, a moderate freeze-drying cycle and an aggressive freeze-drying cycle, which induced a controlled collapse of the sugar matrix. Ovalbumin served as model antigen. The influence of collapse drying and cryo-milling on particle morphology and protein stability was investigated. Cryo-milling generated irregularly shaped particles of size 20-70 µm. The recovery of soluble monomer of ovalbumin was not changed during freeze-drying and after cryo-milling, or after 12 months of storage at 2-8 °C. A slight increase in higher molecular weight aggregates was found in formulations containing the polymer dextran after 12 months of storage at 50 °C. Light obscuration measurements showed an increase in cumulative particle counts after cryo-milling that did not further increase during storage at 2-8 °C for 12 months. The applicability of the cryo-milling process to other therapeutic proteins was shown using recombinant human granulocyte-colony stimulating factor. Collapse freeze-drying and subsequent cryo-milling allows the generation of particles suitable for intradermal powder injection.
authors: Department of Pharmacy, Pharmaceutical Technology and Biopharmaceutics, Ludwig-Maximilians-University , Munich , Germany.
authors: Elsa E
authors: EE
authors: Etzl
authors: Gerhard
authors: G
authors: Winter
authors: Julia
authors: J
authors: Engert
mesh_terms: D000287:Administration, Topical; D005612:Freeze Drying / Q000379:methods*; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage* / Q000737:chemistry; D006801:Humans; D010047:Ovalbumin / Q000008:administration & dosage* / Q000737:chemistry; D010316:Particle Size; D011208:Powders / Q000008:administration & dosage* / Q000737:chemistry; D055550:Protein Stability; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000737:chemistry; D014611:Vaccination / Q000379:methods
chemical_list: D011208:Powders; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D010047:Ovalbumin