Optimization of formulation and device design for carrier-based nasal powder of influenza vaccine to maximize the delivery capability to the target site in the nasal cavity

Abstract

Previously, a nasal powder formulation of the influenza vaccine was proposed to ensure its stability over fifteen months at room temperature and to have sufficient moisture-resistant characteristics to enable handling without special humidity control. In this study, a carrier-based concept: a physical mixture of the antigen powder and the carrier powder, was adopted for this nasal powder formulation. The physical properties of both components were optimized to maximize the delivery capability to the target site located behind the nasal cavity using a human nasal cast model.

Preliminary evaluation with a prototype device (Device A) revealed that the physical properties of the antigen powder influenced the delivery efficiency mainly through their effect on the discharge rate from the device. Since it is obvious that the discharge rate from the device must be secured as a prerequisite for increasing the target site delivery, Device B with an improved discharge rate was developed, and the optimal powder properties were re-evaluated. The delivery rate of antigen powder to the target site was broken down into two elements: the discharge rate from the device and the delivery efficiency of emitted powder to the target site, and then the effect of the particle size of antigen powder and the carrier powder on each element was analyzed separately.

As a result, an optimal particle size region was identified for each element as a design space on a two-dimensional map described by the antigen particle size and the carrier particle size. Besides this analysis, the fine particle fraction (aerodynamic particle size less than 5 μm) was evaluated in a separate experiment considering the risk of invasion into the lung and a condition of particle size to minimize the fine particle fraction was identified. By integrating the results of the above analysis, an optimal space was determined on the two-dimensional map to maximize the delivery efficiency to the target site while minimizing unintended exposure to the lungs.

Materials

Sucrose was purchased from Merck Millipore (Darmstadt, Germany), Trehalose from Hayashibara Co. Ltd. (Tokyo, Japan), HPC-L (140,000 g/mol) and HPC-SSL (40,000 g/mol) from Nippon Soda Co. Ltd. (Tokyo, Japan), Acid Blue 9 from Tokyo Chemical Industries (Tokyo, Japan), Fluorescein sodium salt from Sigma-Aldrich Co., LLC. (Merck KgaA, Darmstadt, Germany), Respitose SV003 from DFE Pharma (Goch, Germany), Dilactose S from the Freund Corporation (Tokyo, Japan), Pearlitol 200SD from Roquette Frères.

Mieda Shiuhei, Kazuhiro Inoue, Atsutoshi Ito, Shuichi Yada, Makoto Miyajima, Toshiro Fukami, Optimization of formulation and device design for carrier-based nasal powder of influenza vaccine to maximize the delivery capability to the target site in the nasal cavity, Journal of Drug Delivery Science and Technology, 2024, 106454, ISSN 1773-2247, https://doi.org/10.1016/j.jddst.2024.106454.