In vitro characterization of the I-neb Adaptive Aerosol Delivery (AAD) system

Abstract

The in vitro characterization of device-related parameters such as the rate of aerosol output, total aerosol output, particle size, and fine particle fraction, is essential when assessing the potential performance of a nebulizer or making comparisons with other nebulizers as they are indicative of potential clinical performance. This article reviews a number of in vitro studies designed to characterize the I-neb Adaptive Aerosol Delivery (AAD) System in terms of drug delivery (particle size, residual, reproducibility, precise dose delivery, dose equivalence), in terms of drug-related performance (osmolality, surface tension, viscosity), and in terms of nebulizer orientation during operation. The results of the in vitro tests of drug delivery indicate that the I-neb AAD System is suitable for delivery of aqueous solutions by nebulization. The evaluation of equivalent doses between the I-neb AAD System (metered dose) and a conventional jet nebulizer (delivered dose), demonstrates that the amount of drug required to deliver the same dose is up to five times less with the I-neb AAD System due to the low residual and controlled drug delivery. The lack of change in osmolality during nebulization might be of importance as it presents an opportunity for delivery of drugs to patients with hyperreactive airways, or where a specific tonicity of the formulation is required. The physicochemical characteristics (surface tension, viscosity) of a number of drugs delivered with the I-neb AAD System highlights some of the demands created by existing and new drug formulations. Finally, the study of the impact of nebulizer orientation shows how important it is to also consider how the nebulizer will actually be physically used by the patient rather than solely under standard conditions used within the laboratory.

FIG. 1.

The I-neb Adaptive Aerosol Delivery (AAD) System. The main components of the device are the mouthpiece, the medication chamber assembly, and the body. The I-neb AAD System has been designed to deliver aerosol with two different breathing pattern algorithms, the Tidal Breathing Mode (TBM) and the Target Inhalation Mode (TIM). In TIM the inspiratory flow through the valve in the mouthpiece is limited to ∼20 L/min.

FIG. 2.

The medication chamber assemblies of the I-neb Adaptive Aerosol Delivery (AAD) System. The metering chamber with the dosing segment is shown to the left, and the nonmetering chamber to the right.

FIG. 3.

Reproducibility of the metered dose of albuterol from fifty 0.3 mL I-neb Adaptive Aerosol Delivery (AAD) System chambers.

FIG. 4.

The relationship between the nebulizer fill volumes for the I-neb Adaptive Aerosol Delivery (AAD) System and an LC Plus jet nebulizer required to achieve equivalent predicted lung doses.

FIG. 5.

Change in osmolality during nebulization shown for the I-neb Adaptive Aerosol Delivery (AAD) System (♦) and an LC Plus jet nebulizer (▪).

FIG. 6.

Surface tensions and viscosities of a number of formulations including small molecules (♦), proteins (▴), suspensions (▪) and liposomes (•).

FIG. 7.

Impact of nebulizer orientation on aerosol delivery shown for the I-neb Adaptive Aerosol Delivery (AAD) System (▪), the Aeroneb Go (○), the eFlow rapid (▴), and the Micro Air NE-U22 (•) nebulizers.