Influenza vaccine powder formulation development: spray-freeze-drying and stability evaluation
Influenza vaccine powder formulation development: spray-freeze-drying and stability evaluation
Published Online: 12 May 2004
Received: 13 January 2004; Revised: 20 February 2004; Accepted: 15 March 2004
Yuh-Fun Maa *, Mahmoud Ameri, Cassandra Shu, Lendon G. Payne, Dexiang Chen
Journal of Pharmaceutical Sciences
Volume 93, Issue 7 , Pages 1912 - 1923
Wiley InterScience
PowderJect Vaccines, Incorporated, 8551 Research Way Boulevard, Middleton, Wisconsin 53562 USA

email: Yuh-Fun Maa (ymaa@alzus.jnj.com)
*Correspondence to Yuh-Fun Maa, PowderJect Vaccines, Incorporated, 8551 Research Way Boulevard, Middleton, Wisconsin 53562 USA. Telephone: 650-564-2104; Fax: 650-564-2700
Keywords
freeze-drying ? vaccines ? formulation ? spray-freeze-drying
Abstract
The purpose of this study was to develop a spray-freeze-drying (SFD) process for preparing an influenza vaccine dry powder formulation suitable for epidermal powder immunization. After preformulation of two types of flu vaccines, their dry-powder formulations were prepared by SFD. Powder properties and physical stability were determined using particle size analysis, tap density measurement, scanning electron microscopy, optical microscopy, and moisture content analysis. Chemical and biochemical stability of vaccine antigens was determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, single radial immunodiffusion assay, and in vivo immunogenicity in a mouse model. We demonstrated that SFD could produce high-density particles - a critical parameter for effective skin penetration. From the stability perspective, the stress posed by SFD was mild because the antigen in the dry powder retained its stability, potency, and immunogenicity. Among several formulations screened, we noted that formulation composition has a significant role in the powder's long-term physical and biochemical stability. One formulation, in particular, containing sub-unit vaccine (45 g of antigen in 1 mg of powder) with a tertiary mixture of trehalose, mannitol, and dextran, exhibited excellent overall stability, including acceptable biochemical stability after being exposed to a highly humid environment. After all, we have not only demonstrated the suitability of SFD to prepare powders for epidermal powder immunization but also developed a systematic formulation development strategy that allowed the optimization of an influenza vaccine dry powder formulation. More important, this study led to the selection of a formulation system that had been successfully tested in a human clinical study. ? 2004 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 93:1912-1923, 2004
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