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.
Garmise
Robert J
RJ
School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Mar
Kevin
K
Crowder
Timothy M
TM
Hwang
C Robin
CR
Ferriter
Matthew
M
Huang
Juan
J
Mikszta
John A
JA
Sullivan
Vincent J
VJ
Hickey
Anthony J
AJ
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