Development of stable influenza vaccine powder formulations: Challenges and possibilities

J-P Amorij, A Huckriede, J Wilschut, H W Frijlink, W L J Hinrichs*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

150 Citations (Scopus)
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Influenza vaccination represents the cornerstone of influenza prevention. However, today all influenza vaccines are formulated as liquids that are unstable at ambient temperatures and have to be stored and distributed under refrigeration. In order to stabilize influenza vaccines, they can be brought into the dry state using suitable excipients, stabilizers and drying processes. The resulting stable influenza vaccine powder is independent of cold-chain facilities. This can be attractive for the integration of the vaccine logistics with general drug distribution in Western as well as developing countries. In addition, a stockpile of stable vaccine formulations of potential vaccines against pandemic viruses can provide an immediate availability and simple distribution of vaccine in a pandemic outbreak. Finally, in the development of new needle-free dosage forms, dry and stable influenza vaccine powder formulations can facilitate new or improved targeting strategies for the vaccine compound. This review represents the current status of dry stable inactivated influenza vaccine development. Attention is given to the different influenza vaccine types (i.e. whole inactivated virus, split, subunit or virosomal vaccine), the rationale and need for stabilized influenza vaccines, drying methods by which influenza vaccines can be stabilized (i.e. lyophilization, spray drying, spray-freeze drying, vacuum drying or supercritical fluid drying), the current status of dry influenza vaccine development and the challenges for ultimate market introduction of a stable and effective dry-powder influenza vaccine.

Original languageEnglish
Pages (from-to)1256-1273
Number of pages18
JournalPharmaceutical Research
Issue number6
Publication statusPublished - 1-Jun-2008


  • Analytical challenges
  • Influenza vaccine
  • Lyophilization
  • Needle-free dosage forms
  • Spray drying
  • Spray-freeze drying
  • Stability
  • Stock piling for pandemics
  • Virosomes
  • dextran
  • dipalmitoylphosphatidylcholine
  • excipient
  • hetastarch
  • inactivated virus vaccine
  • influenza vaccine
  • inulin
  • live vaccine
  • mannitol
  • subunit vaccine
  • trehalose
  • virosome vaccine
  • xylose
  • clinical trial
  • desiccation
  • drug dosage form comparison
  • drug fever
  • drug formulation
  • drug induced headache
  • drug stability
  • dry powder
  • freeze drying
  • human
  • immunogenicity
  • influenza
  • Influenza virus
  • injection site pain
  • injection site swelling
  • methodology
  • priority journal
  • review
  • spray drying
  • supercritical drying
  • supercritical fluid
  • vacuum drying

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