- Yuhji Taquahashi (Division of Cellular and Molecular Toxicology, Center for Biological Safety and Research, National Institute of Health Sciences / email@example.com)
Division of Cellular and Molecular Toxicology, Center for Biological Safety and Research, National Institute of Health Sciences
Inhalation exposure systems for small experimental animals are necessary evaluation tools of efficacy, pharmacokinetics, and safety when developing inhaled drugs. However, the development of inhalants is characterized by high technical barriers and costs. This project aimed to develop an aerosol generator specialized for a pressurized metered-dose inhaler (pMDI) formulation of ciclesonide (CIC), a prodrug-type corticosteroid for asthma. Our results showed that the developed aerosol generator achieved approximately 160 mg/m3 in mass concentration, by using 60 bottles of the pMDI within a one-hour inhalation exposure study. The CIC used in the study was 672 mg in total. The mass median aerodynamic diameter (MMAD) was approximately 1 µm, with less than 2 in geometric standard deviation. Although the amount of test article used was less than 1 g, the aerosol generator achieved approximately 160 mg/m3 in mass concentration, and enough of the CIC was delivered to the rat lungs to allow the visualization of its spatial localization by desorption electrospray ionization–time-of-flight mass spectrometry imaging. We concluded that (i) the aerosol generator was able to drive pMDI accurately, and (ii) the CIC aerosol was delivered to the rodent under appropriate MMAD and concentration; the device’s performance as an excellent nonclinical inhalation exposure system was thus demonstrated. Furthermore, as the device is highly versatile, it would be possible to utilize it when conducting nonclinical inhalation studies at the optimal conditions for various pMDIs. In the future, aerosol generators could reduce costs and shorten the development period of inhaled drugs.