Generating Charged Pharmaceutical Aerosols Intended to Improve Targeted Drug Delivery in Ventilated Infants

Overview

Journal J Aerosol Sci

Date 2015 Aug 15

PMID 26273108

Citations 4

Authors

Landon Holbrook

Michael Hindle

P Worth Longest

Affiliations

Soon will be listed here.

Abstract

The delivery of pharmaceutical aerosols to infants receiving mechanical ventilation is extremely challenging due to small diameter flow passages, low tidal volumes, and frequent exhalation of the aerosol. The use of small charged particles is proposed as a novel method to prevent deposition in ventilator components and foster deposition in the lower infant airways. The objective of this study was to compare the performance of multiple new devices for generating small charged particles that are expected to maximize respiratory drug delivery in ventilated infants. Criteria used to select a leading device included production of a charged aerosol with a mass median aerodynamic diameter (MMAD) ≤ approximately 1.8 μm; low device depositional loss of the aerosol (<20%); particle charge in the range of the Rayleigh limit/100; and high drug output with low performance variability. Proposed new devices were a wick electrospray (WES) system with accelerated cross-flow air; a condensational vapor (CV) system with a charged solution and strong field gradient; and a low flow - induction charger (LF-IC) designed to operate with a modified commercial mesh nebulizer. Based on infant ventilation conditions, flow rates through the devices were in a range of 2-5 L/min and the devices were assessed in terms of depositional drug loss and emitted drug mass; droplet size distribution (DSD) using a Mini-MOUDI; and DSD and net charge with a modified ELPI. Considering the WES, primary limitations were (i) low and variable aerosol production rates and (ii) high device depositional losses. The CV device produced a high quality aerosol with a MMAD of 0.14 μm and a drug delivery rate of 25 μg/min. However, the device was excluded because it failed to produce a charged aerosol. In contrast, the LF-IC produced a 1.6 μm aerosol with high net charge, low device depositional loss (<15% based on recovery), and low variability. In the ELPI size fraction bin nearest the MMAD, the LF-IC produced >100 elementary charges per particle, which was an order of magnitude increase compared to the case of zero charging voltage. In conclusion, the LF-IC was selected as a leading system that is expected to improve aerosol delivery efficiency in ventilated infants through the use of small charged particles.

Citing Articles

In Vitro Determination of the Main Effects in the Design of High-Flow Nasal Therapy Systems with Respect to Aerosol Performance.

Bennett G, Joyce M, Sweeney L, MacLoughlin R Pulm Ther. 2020; 4(1):73-86.

PMID: 32026245 PMC: 6967237. DOI: 10.1007/s41030-018-0054-x.

Devices for Improved Delivery of Nebulized Pharmaceutical Aerosols to the Lungs.

Longest W, Spence B, Hindle M J Aerosol Med Pulm Drug Deliv. 2019; 32(5):317-339.

PMID: 31287369 PMC: 6781258. DOI: 10.1089/jamp.2018.1508.

Experimental Evaluation of Perfluorocarbon Aerosol Generation with Two Novel Nebulizer Prototypes.

Aramendia I, Fernandez-Gamiz U, Lopez-Arraiza A, Rey-Santano C, Mielgo V, Basterretxea F Pharmaceutics. 2019; 11(1).

PMID: 30621300 PMC: 6358822. DOI: 10.3390/pharmaceutics11010019.

In Vitro Assessment of Small Charged Pharmaceutical Aerosols in a Model of a Ventilated Neonate.

Holbrook L, Hindle M, Longest P J Aerosol Sci. 2017; 110:25-35.

PMID: 29276307 PMC: 5737757. DOI: 10.1016/j.jaerosci.2017.05.006.

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