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Formulation of a dry powder influenza vaccine for nasal delivery

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Abstract

The purpose of this research was to prepare a dry powder vaccine formulation containing whole inactivated influenza virus (VIIV) and a mucoadhesive compound suitable for nasal delivery. Powders containing WIIV and either lactose or trehalose were produced by lyophilization. A micro-ball mill was used to reduce the lyophilized cake to sizes suitable for nasal delivery. Chitosan flakes were reduced in size using a cryo-milling technique. Milled powders were sieved between 45 and 125 μm aggregate sizes and characterized for particle size and distribution, morphology, and flow properties. Powders were blended in the micro-ball mill without the ball. Lyophilization followed by milling produced irregularly shaped, polydisperse particles with a median primary particle diameter of ≈21 μm and a yield of ≈37% of particles in the 45 to 125 μm particle size range. Flow properties of lactose and trehalose powders after lyophilization followed by milling and sieving were similar. Cryo-milling produced a small yield of particles in the desired size range (<10%). Lyophilization followed by milling and sieving produced particles suitable for nasal delivery with different physicochemical properties as a function of processing conditions and components of the formulation. Further optimization of particle size and morphology is required for these powders to be suitable for clinical evaluation.

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Author information

Author notes

  1. Timothy M. Crowder

    Present address: Oriel Therapeutics, Inc, 630 Davis Drive, 27713, Durham, NC

Authors and Affiliations

  1. School of Pharmacy, University of North Carolina at Chapel Hill, CB# 7360 Kerr Hall Room 1310, 27599, Chapel Hill, NC

    Robert J. Garmise & Anthony J. Hickey

  2. Becton Dickinson Technologies, 27709, Research Triangle Park, NC

    Kevin Mar, C. Robin Hwang, Matthew Ferriter, Juan Huang, John A. Mikszta & Vincent J. Sullivan

  3. Department of Biomedical Engineering and Mathematics, School of Medicine, University of North Carolina, 27599, Chapel Hill, NC

    Timothy M. Crowder & Anthony J. Hickey

Authors
  1. Robert J. Garmise
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  2. Kevin Mar
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  3. Timothy M. Crowder
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  4. C. Robin Hwang
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  5. Matthew Ferriter
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  6. Juan Huang
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  7. John A. Mikszta
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  8. Vincent J. Sullivan
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  9. Anthony J. Hickey
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Corresponding author

Correspondence to Anthony J. Hickey.

Additional information

Published: March 10, 2006

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Garmise, R.J., Mar, K., Crowder, T.M. et al. Formulation of a dry powder influenza vaccine for nasal delivery. AAPS PharmSciTech 7, 19 (2006). https://doi.org/10.1208/pt070119

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  • DOI: https://doi.org/10.1208/pt070119

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