Metered-dose inhaler product contain therapeutically active ingredients dissolved or suspended in a propellant, a mixture of propellant, or a mixture of solvents, propellants, and/or other excipients in compact pressurized aerosol dispensers. An MDI product may discharge up to several hundred metered doses of one or more drug substances. Depending on the product, each actuation may contain from a few microorganisms (mcg) up to milligrams (mg) of the active ingredients delivered in a volume typically between 25 and 100 microliters.
Although similar in many features to other drug products, MDIs have unique differences with respect to formulation, container, closure, manufacturing, in-process and final controls, and stability. These differences need to be considered during the development program because they can affect the ability of the product to deliver reproducible doses to patients over the life of the product to deliver reproducible doses to patients over the life of the product as well as the product’s efficacy. Some of the unique features of MDIs are listed below:
Current designs of DPI include pre-metered and device-metered DPIs, both of which can be driven by patient inspiration alone or with power-assistance of some type. Pre-metered DPIs contain previously measured doses or dose fractions in some type of units (e.g., single or multiple presentations in blister, capsules, or other cavities) that are subsequently inserted into the device during manufacture or by the patient before use. The dose may be inhaled directly from the pre-metered unit or it may be transferred to a chamber before being inhaled directly from the pre-metered unit or it may be transferred to a chamber before being inhaled by the patient. Device-metered DPIs have an internal reservoir containing sufficient formulation for multiple doses that are metered by the device itself during actuation by the patient. The wide array of DPI designs, many with characteristics unique to the design, will present challenges in developing information in support application. Regardless of the DPI design, the most crucial attributes are the reproducibility of the dose and particle size distribution.