Devices for Improved Delivery of Nebulized Pharmaceutical Aerosols to the Lungs

Overview

Journal J Aerosol Med Pulm Drug Deliv

Specialties Pharmacology
Pulmonary Medicine

Date 2019 Jul 10

PMID 31287369

Citations 20

Authors

Worth Longest

Benjamin Spence

Michael Hindle

Affiliations

Soon will be listed here.

Abstract

Nebulizers have a number of advantages for the delivery of inhaled pharmaceutical aerosols, including the use of aqueous formulations and the ability to deliver process-sensitive proteins, peptides, and biological medications. A frequent disadvantage of nebulized aerosols is poor lung delivery efficiency, which wastes valuable medications, increases delivery times, and may increase side effects of the medication. A focus of previous development efforts and previous nebulizer reviews, has been an improvement of the underlying nebulization technology controlling the breakup of a liquid into droplets. However, for a given nebulization technology, a wide range of secondary devices and strategies can be implemented to significantly improve lung delivery efficiency of the aerosol. This review focuses on secondary devices and technologies that can be implemented to improve the lung delivery efficiency of nebulized aerosols and potentially target the region of drug delivery within the lungs. These secondary devices may (1) modify the aerosol size distribution, (2) synchronize aerosol delivery with inhalation, (3) reduce system depositional losses at connection points, (4) improve the patient interface, or (5) guide patient inhalation. The development of these devices and technologies is also discussed, which often includes the use of computational fluid dynamic simulations, three-dimensional printing and rapid prototype device and airway model construction, realistic experiments, and analysis. Of the devices reviewed, the implementation of streamlined components may be the most direct and lowest cost approach to enhance aerosol delivery efficiency within nonambulatory nebulizer systems. For applications involving high-dose medications or precise dose administration, the inclusion of active devices to control aerosol size, guide inhalation, and synchronize delivery with inhalation hold considerable promise.

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References

Finlay W, Martin A . Recent advances in predictive understanding of respiratory tract deposition. J Aerosol Med Pulm Drug Deliv. 2008; 21(2):189-206. DOI: 10.1089/jamp.2007.0645. View

Skaria S, Smaldone G . Omron NE U22: Comparison between vibrating mesh and jet nebulizer. J Aerosol Med Pulm Drug Deliv. 2010; 23(3):173-80. DOI: 10.1089/jamp.2010.0817. View

Longest P, Tian G, Hindle M . Improving the lung delivery of nasally administered aerosols during noninvasive ventilation-an application of enhanced condensational growth (ECG). J Aerosol Med Pulm Drug Deliv. 2011; 24(2):103-18. PMC: 3123840. DOI: 10.1089/jamp.2010.0849. View

Fink J . Aerosol delivery to ventilated infant and pediatric patients. Respir Care. 2004; 49(6):653-65. View

Wang Y, Li J, Leavey A, ONeil C, Babcock H, Biswas P . Comparative Study on the Size Distributions, Respiratory Deposition, and Transport of Particles Generated from Commonly Used Medical Nebulizers. J Aerosol Med Pulm Drug Deliv. 2016; 30(2):132-140. DOI: 10.1089/jamp.2016.1340. View

Naehrig S, Lang S, Schiffl H, Huber R, Fischer R . Lung function in adult patients with cystic fibrosis after using the eFlow rapid for one year. Eur J Med Res. 2011; 16(2):63-6. PMC: 3353423. DOI: 10.1186/2047-783x-16-2-63. View

DiBlasi R . Clinical Controversies in Aerosol Therapy for Infants and Children. Respir Care. 2015; 60(6):894-914. DOI: 10.4187/respcare.04137. View

Corcoran T . Imaging in Aerosol Medicine. Respir Care. 2015; 60(6):850-5. DOI: 10.4187/respcare.03537. View

Carvalho T, McConville J . The function and performance of aqueous aerosol devices for inhalation therapy. J Pharm Pharmacol. 2016; 68(5):556-78. DOI: 10.1111/jphp.12541. View

10.

Rubin B, FINK J . Aerosol therapy for children. Respir Care Clin N Am. 2001; 7(2):175-213, v. DOI: 10.1016/s1078-5337(05)70030-7. View

11.

Holbrook L, Hindle M, Longest P . In Vitro Assessment of Small Charged Pharmaceutical Aerosols in a Model of a Ventilated Neonate. J Aerosol Sci. 2017; 110:25-35. PMC: 5737757. DOI: 10.1016/j.jaerosci.2017.05.006. View

12.

Sands D, Sapiejka E, Gaszczyk G, Mazurek H . Comparison of two tobramycin nebuliser solutions: pharmacokinetic, efficacy and safety profiles of T100 and TNS. J Cyst Fibros. 2014; 13(6):653-60. DOI: 10.1016/j.jcf.2014.04.006. View

13.

Newman S, Brown J, Steed K, Reader S, Kladders H . Lung deposition of fenoterol and flunisolide delivered using a novel device for inhaled medicines: comparison of RESPIMAT with conventional metered-dose inhalers with and without spacer devices. Chest. 1998; 113(4):957-63. DOI: 10.1378/chest.113.4.957. View

14.

Boyd B, Noymer P, Liu K, Okikawa J, Hasegawa D, Warren S . Effect of gender and device mouthpiece shape on bolus insulin aerosol delivery using the AERx pulmonary delivery system. Pharm Res. 2004; 21(10):1776-82. DOI: 10.1023/b:pham.0000045228.32419.ba. View

15.

Scherer T, Geller D, Owyang L, Tservistas M, Keller M, Boden N . A technical feasibility study of dornase alfa delivery with eFlow® vibrating membrane nebulizers: aerosol characteristics and physicochemical stability. J Pharm Sci. 2010; 100(1):98-109. DOI: 10.1002/jps.22231. View

16.

Dalby R, Spallek M, Voshaar T . A review of the development of Respimat Soft Mist Inhaler. Int J Pharm. 2004; 283(1-2):1-9. DOI: 10.1016/j.ijpharm.2004.06.018. View

17.

Pleasants R, Hess D . Aerosol Delivery Devices for Obstructive Lung Diseases. Respir Care. 2018; 63(6):708-733. DOI: 10.4187/respcare.06290. View

18.

Lenney W, Edenborough F, Kho P, Kovarik J . Lung deposition of inhaled tobramycin with eFlow rapid/LC Plus jet nebuliser in healthy and cystic fibrosis subjects. J Cyst Fibros. 2010; 10(1):9-14. DOI: 10.1016/j.jcf.2010.08.019. View

19.

Gessler T, Ghofrani H, Held M, Klose H, Leuchte H, Olschewski H . The safety and pharmacokinetics of rapid iloprost aerosol delivery via the BREELIB nebulizer in pulmonary arterial hypertension. Pulm Circ. 2017; 7(2):505-513. PMC: 5467944. DOI: 10.1177/2045893217706691. View

20.

Hess D . The mask for noninvasive ventilation: principles of design and effects on aerosol delivery. J Aerosol Med. 2007; 20 Suppl 1:S85-98. DOI: 10.1089/jam.2007.0574. View