Formulation of a dry powder influenza vaccine for nasal delivery.
The purpose of this research was to prepare a dry powder vaccine formulation containing whole inactivated influenza virus (WIIV) 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 microm 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 approximately 21 microm and a yield of approximately 37% of particles in the 45 to 125 microm 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.
School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Robert J
RJ
Garmise
Kevin
K
Mar
Timothy M
TM
Crowder
C Robin
CR
Hwang
Matthew
M
Ferriter
Juan
J
Huang
John A
JA
Mikszta
Vincent J
VJ
Sullivan
Anthony J
AJ
Hickey
D000281:Administration, Intranasal; D005612:Freeze Drying; D007252:Influenza Vaccines / Q000008:administration & dosage*; D010316:Particle Size; D011208:Powders; D014199:Trehalose / Q000008:administration & dosage
D007252:Influenza Vaccines; D011208:Powders; D014199:Trehalose