title: Formulation of a dry powder influenza vaccine for nasal delivery.
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.
authors.affiliation: School of Pharmacy, University of North Carolina at Chapel Hill, CB# 7360 Kerr Hall Room 1310, 27599, Chapel Hill, NC.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Garmise
authors.affiliation: Becton Dickinson Technologies, 27709, Research Triangle Park, NC.
authors.forename: Kevin
authors.initials: K
authors.lastname: Mar
authors.affiliation: Department of Biomedical Engineering and Mathematics, School of Medicine, University of North Carolina, 27599, Chapel Hill, NC.
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Crowder
authors.affiliation: Becton Dickinson Technologies, 27709, Research Triangle Park, NC.
authors.forename: C Robin
authors.initials: CR
authors.lastname: Hwang
authors.affiliation: Becton Dickinson Technologies, 27709, Research Triangle Park, NC.
authors.forename: Matthew
authors.initials: M
authors.lastname: Ferriter
authors.affiliation: Becton Dickinson Technologies, 27709, Research Triangle Park, NC.
authors.forename: Juan
authors.initials: J
authors.lastname: Huang
authors.affiliation: Becton Dickinson Technologies, 27709, Research Triangle Park, NC.
authors.forename: John A
authors.initials: JA
authors.lastname: Mikszta
authors.affiliation: Becton Dickinson Technologies, 27709, Research Triangle Park, NC.
authors.forename: Vincent J
authors.initials: VJ
authors.lastname: Sullivan
authors.affiliation: School of Pharmacy, University of North Carolina at Chapel Hill, CB# 7360 Kerr Hall Room 1310, 27599, Chapel Hill, NC. ahickey@unc.edu.|Department of Biomedical Engineering and Mathematics, School of Medicine, University of North Carolina, 27599, Chapel Hill, NC. ahickey@unc.edu.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Hickey
keywords: Intranasal delivery; dry powder; influenza vaccine; lyophilization; mucoadhesive