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Drying-Induced Variations in Physico-Chemical Properties of Amorphous Pharmaceuticals and Their Impact on Stability II: Stability of a Vaccine

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Abstract

Objectives

To investigate the impact of drying method on the storage stability of dried vaccine formulations.

Materials and Methods

A sucrose-based formulation of a live attenuated virus vaccine of a parainfluenza strain, with and without surfactant, was dried from by different methods; freeze drying, spray drying and foam drying. Dried powders were characterized by differential scanning calorimetry, specific surface area (SSA) analysis and by electron spectroscopy for chemical analysis (ESCA) to evaluate vaccine surface coverage in the dried formulations. Dried formulations were subjected to storage stability studies at 4, 25 and 37°C. The vaccine was assayed initially and at different time points to measure virus-cell infectivity, and the degradation rate constant of the vaccine in different dried preparations was determined.

Results

SSA was highest with the spray dried preparation without surfactant (∼ 2.8 m2/g) and lowest in the foam dried preparations (with or without surfactant) (∼ 0.1 m2/g). Vaccine surface coverage was estimated based on ESCA measurements of nitrogen content. It was predicted to be highest in the spray dried preparation without surfactant and lowest in the foam with surfactant. Stability studies conducted at 25°C and 37°C showed that the vaccine was most stable in the foam dried preparation with surfactant and least stable in spray dried preparations without surfactant and in all freeze dried preparations regardless of the presence of surfactant. Addition of surfactant did lower the SSA and vaccine surface coverage in freeze dried preparations but still did not improve storage stability.

Conclusions

In drying methods that did not involve a freezing step, good storage stability of Medi 534 vaccine in the dried form was found with low SSA and low vaccine surface accumulation, both of which integrate into low fraction of vaccine at the surface. Ice appears to be a major destabilizing influence.

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Acknowledgements

We would like to acknowledge MedImmune Vaccines for financial support for this project. We would also like to acknowledge Dr. Daniel Goberman from the Surface Sciences Laboratory in the Institute for Materials Sciences at the University of Connecticut for his assistance with use of the VG ESCALAB MK II series Spectrometer.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, University of Connecticut, Storrs, Connecticut, 06269, USA

    Ahmad M. Abdul-Fattah, Devendra S. Kalonia & Michael J. Pikal

  2. Formulation Development, MedImmune Vaccines, Mountain view, California, 94043, USA

    Vu Truong-Le, Luisa Yee, Emilie Pan & Yi Ao

  3. Drug Product & Device Development, AMGEN, Thousand Oaks, CA

    Ahmad M. Abdul-Fattah

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  1. Ahmad M. Abdul-Fattah
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  2. Vu Truong-Le
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  3. Luisa Yee
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Correspondence to Michael J. Pikal.

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Abdul-Fattah, A.M., Truong-Le, V., Yee, L. et al. Drying-Induced Variations in Physico-Chemical Properties of Amorphous Pharmaceuticals and Their Impact on Stability II: Stability of a Vaccine. Pharm Res 24, 715–727 (2007). https://doi.org/10.1007/s11095-006-9191-2

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  • DOI: https://doi.org/10.1007/s11095-006-9191-2

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