PlumX Metrics
Embed PlumX Metrics

Predicting Lung Deposition of Extrafine Inhaled Corticosteroid-Containing Fixed Combinations in Patients with Chronic Obstructive Pulmonary Disease Using Functional Respiratory Imaging: An in Silico Study

Journal of Aerosol Medicine and Pulmonary Drug Delivery, ISSN: 1941-2703, Vol: 34, Issue: 3, Page: 204-211
2021
  • 15
    Citations
  • 0
    Usage
  • 27
    Captures
  • 0
    Mentions
  • 0
    Social Media
Metric Options:   Counts1 Year3 Year

Metrics Details

Article Description

Background: Functional respiratory imaging (FRI) is a computational fluid dynamics-based technique using three-dimensional models of human lungs and formulation profiles to simulate aerosol deposition. Methods: FRI was used to evaluate lung deposition of extrafine beclomethasone dipropionate (BDP)/formoterol fumarate (FF)/glycopyrronium bromide (GB) and extrafine BDP/FF delivered through pressurized metered dose inhalers and to compare results with reference gamma scintigraphy data. FRI combined high-resolution computed tomography scans of 20 patients with moderate-to-severe chronic obstructive pulmonary disease (mean forced expiratory volume in 1 second 42% predicted) with in silico computational flow simulations, and incorporated drug delivery parameters to calculate aerosol airway deposition. Inhalation was simulated using profiles obtained from real-life measurements. Results: Total lung deposition (proportion deposited in intrathoracic region) was similarly high for both products, with mean ± standard deviation (SD) values of 31.0% ± 5.7% and 28.1% ± 5.2% (relative to nominal dose) for BDP/FF/GB and BDP/FF, respectively. Pairwise comparison of the deposition of BDP and FF gave a mean intrathoracic BDP/FF/GB:BDP/FF deposition ratio of 1.10 (p = 0.0405). Mean intrathoracic, central and peripheral deposition ratios for BDP were 1.09 (95% confidence interval [CI]: 1.05-1.14), 0.92 (95% CI: 0.89-0.96), and 1.20 (95% CI: 1.15-1.26), respectively, and for FF were 1.11 (95% CI: 1.07-1.15), 0.94 (95% CI: 0.91-0.98), and 1.21 (95% CI: 1.15-1.27), within the bioequivalence range (0.80-1.25) for intrathoracic and central regions, and slightly exceeding the upper boundary in the peripheral region. Mean ± SD central:peripheral deposition (C:P) was 0.48 ± 0.13 for BDP/FF/GB and 0.62 ± 0.17 for BDP/FF, indicating a higher proportion of drug deposition in the small airways than in the large airways. Conclusion: FRI demonstrated similar deposition patterns for extrafine BDP/FF/GB and BDP/FF, with both having a high lung deposition. Moreover, the deposition patterns of BDP and FF were similar in both products. Furthermore, the C:P ratios of both products indicated a high peripheral deposition, supporting small airway targeting and delivery of these two extrafine fixed combinations, with a small difference in ratios potentially due to mass median aerodynamic diameters.

Bibliographic Details

Usmani, Omar S; Mignot, Benjamin; Kendall, Irvin; Maria, Roberta De; Cocconi, Daniela; Georges, George; Scichilone, Nicola

Mary Ann Liebert Inc

Medicine; Pharmacology, Toxicology and Pharmaceutics

Provide Feedback

Have ideas for a new metric? Would you like to see something else here?Let us know