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Excipient-free isoniazid aerosol administration in mice: Evaporation-nucleation particle generation, pulmonary delivery and body distribution.
- Source :
-
International journal of pharmaceutics [Int J Pharm] 2019 May 30; Vol. 563, pp. 101-109. Date of Electronic Publication: 2019 Mar 27. - Publication Year :
- 2019
-
Abstract
- 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 <superscript>6</superscript> cm <superscript>-3</superscript> , 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%).<br /> (Copyright © 2019 Elsevier B.V. All rights reserved.)
- Subjects :
- Administration, Inhalation
Aerosols
Animals
Biological Availability
Liver metabolism
Lung metabolism
Male
Mice
Particle Size
Tissue Distribution
Antitubercular Agents administration & dosage
Antitubercular Agents chemistry
Antitubercular Agents pharmacokinetics
Isoniazid administration & dosage
Isoniazid chemistry
Isoniazid pharmacokinetics
Subjects
Details
- Language :
- English
- ISSN :
- 1873-3476
- Volume :
- 563
- Database :
- MEDLINE
- Journal :
- International journal of pharmaceutics
- Publication Type :
- Academic Journal
- Accession number :
- 30928214
- Full Text :
- https://doi.org/10.1016/j.ijpharm.2019.03.050