Formulation of a dry powder influenza vaccine for nasal delivery

• Published in: AAPS PharmSciTech Vol. 7; no. 1; p. E19
• Main Authors: Garmise, Robert J, Mar, Kevin, Crowder, Timothy M, Hwang, C Robin, Ferriter, Matthew, Huang, Juan, Mikszta, John A, Sullivan, Vincent J, Hickey, Anthony J
• Format: Journal Article
• Language: English
• Published: United States 10.03.2006
• Subjects: Administration, Intranasal; Freeze Drying; Influenza Vaccines - administration & dosage; Particle Size; Powders; Trehalose - administration & dosage
• ISSN: 1530-9932
• DOI: 10.1208/pt070103

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.