Physical and immunogenic stability of spray freeze-dried influenza vaccine powder for pulmonary delivery: comparison of inulin, dextran, or a mixture of dextran and trehalose as protectants.
One of the advantages of dry influenza vaccines over conventional liquid influenza vaccines is that they can be used for alternative routes of administration. Previous studies showed that spray freeze-drying is an excellent technique to prepare vaccine containing powders for pulmonary delivery (J.P. Amorij, V. Saluja, A.H. Petersen, W.L.J. Hinrichs, A. Huckriede, H.W. Frijlink, Pulmonary delivery of an inulin-stabilized influenza subunit vaccine prepared by spray-freeze drying induces systemic, mucosal humoral as well as cell-mediated immune responses in BALB/c mice, Vaccine 25 (2007) 8707-8717; S.A. Audouy, G. van der Schaaf, W.L.J. Hinrichs, H.W. Frijlink, J. Wilschut, A. Huckriede. Development of a dried influenza whole inactivated virus vaccine for pulmonary immunization, Vaccine (2011)). The aim of this study was to investigate the physical and immunogenic stability of spray freeze-dried whole inactivated virus influenza vaccine prepared by using inulin, dextran, and a mixture of dextran and trehalose as protectants. Physical and biochemical characteristics of the vaccine powder were maintained at temperatures up to 30 °C for 3 months. In addition, in vivo data indicate that also, the immunogenic properties of the vaccine were maintained under these storage conditions. On the other hand, in vivo results also revealed that subtle changes in powder characteristics were induced during storage at 30 °C. However, laser diffraction measurements showed that problems associated with these subtle changes can be overcome by using dry powder inhalers with an efficient powder dispersing capacity.
Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Groningen, The Netherlands. Electronic address: s.murugappan@rug.nl.
Senthil
S
Murugappan
Harshad P
HP
Patil
Gaurav
G
Kanojia
Wouter
W
ter Veer
Tjarko
T
Meijerhof
Henderik W
HW
Frijlink
Anke
A
Huckriede
Wouter L J
WL
Hinrichs
D000818:Animals; D002626:Chemistry, Pharmaceutical; D003911:Dextrans / Q000737:chemistry*; D004339:Drug Compounding; D004355:Drug Stability; D004356:Drug Storage; D058995:Dry Powder Inhalers; D005079:Excipients / Q000737:chemistry; D005260:Female; D005612:Freeze Drying; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology; D007444:Inulin / Q000737:chemistry*; D051379:Mice; D008807:Mice, Inbred BALB C; D011208:Powders; D013696:Temperature; D014199:Trehalose / Q000737:chemistry*
D003911:Dextrans; D005079:Excipients; D007252:Influenza Vaccines; D011208:Powders; D007444:Inulin; D014199:Trehalose
Antigen stability; Dextran; Influenza vaccine; Inulin; Physical stability; Pulmonary powder; Trehalose