Modelling Drug Delivery to the Small Airways: Optimization Using Response Surface Methodology.

Publisher: Kluwer Academic/Plenum Publishers Country of Publication: United States NLM ID: 8406521 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1573-904X (Electronic) Linking ISSN: 07248741 NLM ISO Abbreviation: Pharm Res Subsets: MEDLINE

Publication: 1999- : New York, NY : Kluwer Academic/Plenum Publishers
Original Publication: Stuttgart ; New York : Thieme, c1984-

Particle Size* ; Pulmonary Disease, Chronic Obstructive*/drug therapy ; Pulmonary Disease, Chronic Obstructive*/metabolism ; Drug Delivery Systems*/methods ; Lung*/metabolism ; Computer Simulation* ; Tidal Volume*; Humans ; Administration, Inhalation ; Models, Biological ; Aerosols

Aim: The aim of this in silico study was to investigate the effect of particle size, flow rate, and tidal volume on drug targeting to small airways in patients with mild COPD.
Method: Design of Experiments (DoE) was used with an in silico whole lung particle deposition model for bolus administration to investigate whether controlling inhalation can improve drug delivery to the small conducting airways. The range of particle aerodynamic diameters studied was 0.4 - 10 µm for flow rates between 100 - 2000 mL/s (i.e., low to very high), and tidal volumes between 40 - 1500 mL.
Results: The model accurately predicted the relationship between independent variables and lung deposition, as confirmed by comparison with published experimental data. It was found that large particles (~ 5 µm) require very low flow rate (~ 100 mL/s) and very small tidal volume (~ 110 mL) to target small conducting airways, whereas fine particles (~ 2 µm) achieve drug targeting in the region at a relatively higher flow rate (~ 500 mL/s) and similar tidal volume (~ 110 mL).
Conclusion: The simulation results indicated that controlling tidal volume and flow rate can achieve targeted delivery to the small airways (i.e., > 50% of emitted dose was predicted to deposit in the small airways), and the optimal parameters depend on the particle size. It is hoped that this finding could provide a means of improving drug targeting to the small conducting airways and improve prognosis in COPD management.
(© 2024. The Author(s).)

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Keywords: design of experiment; particle deposition model; particle size; pulmonary drug delivery; small airway targeting

0 (Aerosols)

Date Created: 20240516 Date Completed: 20240624 Latest Revision: 20241102

20241102

PMC11525259

10.1007/s11095-024-03706-1

38755398