TY - JOUR

T1 - Excipient-free isoniazid aerosol administration in mice: Evaporation-nucleation particle generation, pulmonary delivery and body distribution

AU - Valiulin, S. V.

AU - Onischuk, A. A.

AU - Baklanov, A. M.

AU - Dubtsov, S. N.

AU - An'kov, S. V.

AU - Tolstikova, T. G.

AU - Plokhotnichenko, M. E.

AU - Dultseva, G. G.

AU - Mazunina, P. S.

N1 - Publisher Copyright: © 2019 Elsevier B.V.

PY - 2019/5/30

Y1 - 2019/5/30

N2 - 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%).

AB - 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%).

KW - Aerosol

KW - Isoniazid

KW - Mice

KW - Pharmacokinetics

KW - Pulmonary administration

KW - Lung/metabolism

KW - Isoniazid/administration & dosage

KW - Administration, Inhalation

KW - Biological Availability

KW - Male

KW - Particle Size

KW - Tissue Distribution

KW - Animals

KW - Liver/metabolism

KW - Aerosols

KW - Antitubercular Agents/administration & dosage

KW - VIVO ANIMAL-MODELS

KW - DRUG-DELIVERY

KW - DEPOSITION

KW - TUBERCULOSIS

KW - DIFFUSION BATTERY

KW - THERAPY

KW - SIZE DISTRIBUTION

KW - INHALATION DELIVERY

KW - INFECTION MODEL

KW - PHARMACOKINETICS

UR - http://www.scopus.com/inward/record.url?scp=85063754525&partnerID=8YFLogxK

U2 - 10.1016/j.ijpharm.2019.03.050

DO - 10.1016/j.ijpharm.2019.03.050

M3 - Article

C2 - 30928214

AN - SCOPUS:85063754525

VL - 563

SP - 101

EP - 109

JO - International Journal of Pharmaceutics

JF - International Journal of Pharmaceutics

SN - 0378-5173

ER -