Preparation of influenza vaccine antigen powder that can withstand exposure to humid conditions

Shogo Nakamura¹, Mitsuhide Tanimoto¹, Kaori Shinoda², Kazuhiro Inoue¹, Shuichi Yada¹ & Shuichi Ando¹

¹Formulation Technology Research Laboratories, Daiichi Sankyo Co., Ltd., 1-2-58, Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan

²Vaccine Research Laboratories, Kitasato Daiichi Sankyo Vaccine Co., Ltd., 1-16-13, Kitakasai, Edogawa-ku, Tokyo 134-0081, Japan

Summary

It is important to develop a powder vaccine instead of a liquid formulation, because fine powders can be delivered to the target site of the nasal cavity by airflow. However, it is difficult to maintain the dry state of the powders during the manufacturing operation because of the hygroscopicity of stabilizers. We developed a stable powder nasal vaccine formulation that can withstand exposure to humid conditions. One of its key features is the improvement in the robustness of the antigen stabilizer’s glass structure by the addition of hydroxypropylcellulose (HPC). We confirmed that the glassy state of sucrose plays an important role in protecting the antigen from thermal stress during storage. The addition of HPC to amorphous sucrose preserved the glass structure during storage at 25ºC/30% relative humidity (RH) for 4 days, while crystallization occurred in amorphous sucrose without HPC. The antigen powder prepared with sucrose and HPC maintained antigen activity even after storage at 25ºC/30% RH for 4 days. These results indicate that adding HPC maintained antigen activity in the powder formulation even after storage under humid conditions by improving the robustness of the glass structure of sucrose. This finding is useful for the commercialization of the nasal powder vaccine product.