A known alternative to scintigraphy is FRI (functional respiratory imaging) deposition. The technology that combines HRCT scans and CFD (computational fluid dynamics) calculations, has been used ample times over the past twelve years in deposition studies. Very recently, these results have been collected, scrutinized and compared with scintigraphy data available in the literature for the same drugs/devices in similar populations. It is exciting to say: the results are consistently equivalent. The results of the initial investigation are presented in the table below indicating that for no matter which respiratory disease and, no matter which compound or device, FRI deposition shows the same.
Table 1: Lung deposition results (expressed as percentage of labelled dose (% LD) for FRI deposition and scintigraphy in different disease populations and for different compounds and devices.
|Product||FRI [%]||Scintigraphy [%]|
|Foster in COPD||28 3||31-34 1,2|
|Flutiform in Asthma||42 5||41 4|
|Symbicort in Asthma||23 5||22 6|
|QVAR in Asthma||54 †||53 7|
|iNeb nebulization||45 9||42 8|
|eFlow nebulization||18 9||17 10|
|LC Sprint nebulization||9 12||10-15 11|
|Akita nebulization||34 12||31 11,13|
The implications of these findings are profound. Given the low cost (an order of magnitude lower compared to scintigraphy studies) and short time-spans (counted in weeks), the respiratory industry gets the challenging opportunity to investigate an immense amount of deposition scenarios in a uniquely controlled way. It is due to the fact that its processes are structured that patient inclusion becomes obsolete. The benefits of FRI deposition go beyond the price and time. The technology allows three-dimensional, high resolution visualizations of the patient specific lungs and airways where regional deposition can be analysed (on a lobar or airway level) without the need of radiolabelling. Since the three-dimensional representation of deposition in actual patient airways is very intuitive, its applications easily extend to marketing and communication (e.g. towards the regulatory agencies) purposes.
Figure 3: One patient’s specific airways coupled to an MDI device showing the local deposition concentration of two different dosages of a compound.
The technology aims to fill the current knowledge gaps and to improve drug delivery in the best way possible. The knowledge that FRI deposition and scintigraphy are equivalent, is a promising aspect in the respiratory field. The findings will be submitted for publication soon. Having FRI as a cheap and reliable tool will allow drug developers to look at deposition from many more angles compared to the past. This will optimise lung deposition in the future and patients will feel the benefit of having maximum efficacy with a minimal amount of side effect. Nonetheless, development never stops and FLUIDDA will continue its research in this area with the goal to optimise respiratory drug development even further.
Movie 1: One patient’s specific airways coupled to an MDI device showing the transport of particles over time as well as the build-up of the local deposition concentration.
1. De Maria, R. et al. Foster®: A High-Efficiency Combination Metered Dose Inhaler with Consistent Particle Size Distribution at Alternative Flow Rates. Prod. Ther. 4, (2014).
2. De Backer, W. et al. Lung Deposition of BDP/Formoterol HFA pMDI in Healthy Volunteers, Asthmatic, and COPD Patients. Aerosol Med. Pulm. Drug Deliv. 23, 137–148 (2010).
3. Usmani, O. et al. Lung deposition of extrafine inhaled corticosteroid (ICS)-containing fixed combinations drug in COPD patients using Functional Respiratory Imaging. Respir. Soc. (2018).
4. Kappeler, D. et al. Lung deposition of fluticasone propionate/formoterol administered via a breath-triggered inhaler. Respir. J. 50, PA522 (2017).
5. Iwanaga, T. et al. Aerosol Deposition of Inhaled Corticosteroids/Long-Acting β2-Agonists in the Peripheral Airways of Patients with Asthma Using Functional Respiratory Imaging, a Novel Imaging Technology. Ther. 3, 219–231 (2017).
6. Hirst, P. H., Bacon, R. E., Pitcairn, G. R., Silvasti, M. & Newman, S. P. A comparison of the lung deposition of budesonide from Easyhaler, Turbuhaler and pMDI plus spacer in asthmatic patients. Med. 95, 720–727 (2001).
7. Leach, C. L., Kuehl, P. J., Chand, R. & McDonald, J. D. Respiratory Tract Deposition of HFA-Beclomethasone and HFA-Fluticasone in Asthmatic Patients. Aerosol Med. Pulm. Drug Deliv. 29, 127–133 (2016).
8. Nikander, K., Prince, I., Coughlin, S., Warren, S. & Taylor, G. Mode of Breathing—Tidal or Slow and Deep—through the I-neb Adaptive Aerosol Delivery (AAD) System Affects Lung Deposition of 99mTc-DTPA. Aerosol Med. Pulm. Drug Deliv. 23, S-37 (2010).
9. Hull, D., Black, A. & Vos, W. Use of computational fluid dynamics (CFD) to model aerosol deposition in the lungs of patients with cystic fibrosis. Cyst. Fibros. Soc. (2018).
10. Lenney, W., Edenborough, F., Kho, P. & Kovarik, J. M. Lung deposition of inhaled tobramycin with eFlow rapid/LC Plus jet nebuliser in healthy and cystic fibrosis subjects. Cyst. Fibros. 10, 9–14 (2011).
11. Fischer, A., Stegemann, J., Scheuch, G. & Siekmeier, R. Novel devices for individualized controlled inhalation can optimize aerosol therapy in efficacy, patient care and power of clinical trials. J. Med. Res. 14 Suppl 4, 71–77 (2009).
12. Munro, S., Main, M. & Vos, W. The application of computational deposition modelling, to study the impact of delivering a model standardised inhalation product using a variety of different delivery platforms to the lungs of IPF patients with varying disease severity. What is best for the patient? Drug Deliv. Lungs (2017).
13. Müllinger, B. et al. Intra-pulmonal deposition of two different tobramycin formulations. Cyst. Fibros. 4, S53 (2005).
†. Data on file