Advances in metered dose inhaler technology: hardware development

Abstract

Pressurized metered dose inhalers (MDIs) were first introduced in the 1950s and they are currently widely prescribed as portable systems to treat pulmonary conditions. MDIs consist of a formulation containing dissolved or suspended drug and hardware needed to contain the formulation and enable efficient and consistent dose delivery to the patient. The device hardware includes a canister that is appropriately sized to contain sufficient formulation for the required number of doses, a metering valve capable of delivering a consistent amount of drug with each dose delivered, an actuator mouthpiece that atomizes the formulation and serves as a conduit to deliver the aerosol to the patient, and often an indicating mechanism that provides information to the patient on the number of doses remaining. This review focuses on the current state-of-the-art of MDI hardware and includes discussion of enhancements made to the device's core subsystems. In addition, technologies that aid the correct use of MDIs will be discussed. These include spacers, valved holding chambers, and breath-actuated devices. Many of the improvements discussed in this article increase the ability of MDI systems to meet regulatory specifications. Innovations that enhance the functionality of MDIs continue to be balanced by the fact that a key advantage of MDI systems is their low cost per dose. The expansion of the health care market in developing countries and the increased focus on health care costs in many developed countries will ensure that MDIs remain a cost-effective crucial delivery system for treating pulmonary conditions for many years to come.

Fig. 1

Schematic of the Spraymiser™ valve

Fig. 2

a Formulation delivery for a CFC albuterol MDI. b Formulation delivery for a HFA albuterol MDI. Adapted from Ross and Gabrio, 1999 (5)

Fig. 3

The Easifill™ valve, which fills via open channels in its stem. Drawing courtesy of Bespak plc

Fig. 4

A schematic of the 3M Face Seal Valve™ utilizing a virtual metering chamber. The drawing on the left shows the valve in the “at rest” position; the drawing on the right shows the valve in the “during actuation” position. Drawing courtesy of 3M Healthcare Ltd.

Fig. 5

Schematic of an MDI press-and-breathe actuator. Drawing courtesy of 3M Healthcare Ltd.

Fig. 6

The influence of valve size and nozzle orifice diameter on the fine particle fraction delivered using HFA 134a solution formulation of 0.167% (w/w) beclomethasone dipropionate and 8% (w/w) ethanol

Fig. 7

Schematic of the 3M Autohaler™ breath-actuated inhaler. During priming, a spring is compressed and pushes on the canister, but the canister is prevented from moving by the rocker (in pink) which is held in place by the catch (in blue). During inhalation, the patient airflow moves a vane (in yellow) which releases the catch and allows for the rocker to rotate. At this point, the energy stored in the spring during priming depresses the canister relative to the valve and the dose is discharged to the patient. Drawing courtesy of 3M Healthcare Ltd.

Fig. 8

Schematic of the K-Valve™ breath-actuation system. The image to the left shows the plastic tube at rest (the valve tip would be inserted at the top of the open tube). The middle image shows the plastic tube in the “kinked” position which occurs after the patient depresses the canister to retain the metered dose. A breath-actuated triggering system is then used to un-kink the tube to release the dose as shown in the image on the right. Drawing courtesy of Clinical Designs Ltd.

Fig. 9

An exploded view of the four components of a Trudell Medical International top mount actuation indicator. Drawing courtesy of Trudell Medical International