Excipient-free isoniazid aerosol administration in mice: Evaporation-nucleation particle generation, pulmonary delivery and body distribution

S. V. Valiulin, A. A. Onischuk, A. M. Baklanov, S. N. Dubtsov, S. V. An'kov, T. G. Tolstikova, M. E. Plokhotnichenko, G. G. Dultseva, P. S. Mazunina

Результат исследования: Научные публикации в периодических изданияхстатья

Аннотация

Excipient-free isoniazid aerosol formation and pulmonary delivery in mice are studied. An evaporation-nucleation route is used for the generation of isoniazid aerosol. Particle diameters and number concentrations are measured with an aerosol spectrometer consisting of a diffusion battery, condensation chamber, and photoelectric counter. The pulmonary delivery of isoniazid particles is studied in both nose-only (NO) and whole-body (WB) inhalation chambers for the particle mean diameter and number concentration to be 600 nm and 6 × 10 6 cm −3 , respectively. It is found that the rate of drug systemic absorption in the WB chamber is 27% higher than that for the NO one because of an additional consumption of drug orally from the fur in the WB chamber. The particle deposition efficiency ε in the mouse respiratory tract is measured as a function of mean diameter. The quantity ε is equal to 0.7 for the particle diameter d = 10 nm and decreases to 0.2 with the diameter increasing to 300 nm, and then, at d > 300 nm the deposition efficiency increases with diameter to 0.5 at d = 2000 nm. The bioavailability of the aerosol form of isoniazid (72 ± 10%) is very close to that for the per-oral form (61 ± 10%).

Язык оригиналаанглийский
Страницы (с-по)101-109
Число страниц9
ЖурналInternational Journal of Pharmaceutics
Том563
DOI
СостояниеОпубликовано - 30 мая 2019

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