Aerosol in this context is a dosage form consisting of a liquid or solid preparation packaged under pressure and intended for administration as a fine mist. The descriptive term aerosol also refers to the fine mist of small droplets or solid particles that are emitted from the product. Inhalation aerosols, also known as MDIs, are preparations characterized by dispersion of the active pharmaceutical ingredient into the airways during oral inspiration for either local or systemic effect, and nasal aerosols, also known as nasal MDIs, are characterized by deposition in the nasal cavity for either local or systemic effect.

An aerosol formulation typically contains drug substance(s) dissolved or suspended in a propellant(s) or a mixture of propellant(s) and co-solvent(s) and possibly other suitable excipients. An inhalation aerosol drug product, commonly known as a metered-dose inhaler, delivers a specified amount and quality of therapeutically active ingredient(s) upon activation of an accurately metered valve system. General quality tests for inhalation aerosol drug products should include the following (see section IV later in this chapter for more detailed discussions of each test):

Inhalation solution drug products typically are water-based and are sterile preparations. They are intended for delivery to the lungs by nebulization with a specified external nebulizer. Such drug preparations typically are packaged in single-dose semipermeable containers and also include protective packaging to minimize ingress of volatile foreign contaminants, loss of solvent, and exposure to oxygen and light. Nebulization involves continuous generation and delivery to the patient of a fine mist of aqueous droplets containing a drug solution by means of ultrasonic energy, Venturi effect, or other appropriate mechanical/electrical means. General quality tests for inhalation solutions should include the following (see section IV later in this chapter for more detailed discussions of each test):

Inhalation suspension drug products typically are water-based and are sterile preparations. They are intended for delivery to the lungs by nebulization with a specified external nebulizer. Such drug preparations typically are packaged in single-dose semipermeable containers and also include protective packaging to minimize ingress of volatile foreign contaminants, loss of solvent, and exposure to oxygen and light. Nebulization involves continuous generation and delivery to the patient of a fine mist of aqueous droplets containing the formulation components by means of ultrasonic energy, Venturi effect, or other appropriate mechanical means. General quality tests for inhalation suspensions should include the following (see section IV later in this chapter for more detailed discussions of each test):

Solution for inhalation drug products typically are water-based and are sterile preparations. Upon dilution, in accordance with labeling, including identity and amount of dilution vehicle, they are intended for delivery to the lungs by nebulization using an external nebulizer. Such drug preparations typically are packaged in single-dose semipermeable containers and also include a protective packaging to minimize ingress of volatile foreign contaminants, loss of solvent, and exposure to oxygen and light. Nebulization involves continuous generation and delivery to the patient of a fine mist of aqueous droplets containing the formulation components by means of ultrasonic energy, Venturi effect, or other appropriate mechanical/electrical means. General quality tests for solutions for inhalation should include the following (see section IV later in this chapter for more detailed discussions of each test):

Drug for Inhalation Solution is a (specified color) drug powder formulation that upon the addition of a suitable vehicle, in accordance with labeling, including identity and amount of dilution vehicle, yields a solution conforming in all respects to the Inhalation Solution requirements. General quality tests for drug for inhalation solutions should include the following (see section IV later in this chapter for more detailed discussions of each test):

Inhalation spray drug products typically are water-based liquid formulations packaged in a compact container–closure system containing an integral spray pump unit that upon activation delivers an accurately metered amount of fine mist of droplets of the formulation. The droplets can be generated by various means such as mechanical action, power assistance, or energy from the patient’s inspiration. The mechanisms by which they generate droplets distinguish the various types of inhalation sprays. These drug products may be unit-dose or multidose presentations. Inhalation spray drug products may be designed as premetered or device-metered presentations. A premetered unit contains a previously measured amount of liquid formulation in an individual container (e.g., a blister) that is inserted in the device by the patient before use. A device-metered product contains sufficient amount of liquid formulation for a prescribed number of doses in a reservoir, and each dose is delivered as an accurately metered spray by the device throughout the unit’s life. General quality tests for inhalation sprays should include the following (see section IV later in this chapter for more detailed discussions of each test):

Inhalation powder drug products, commonly known as dry powder inhalers (DPIs), dispense powders for inhalation with the use of a device that aerosolizes and delivers an accurately metered amount of active ingredient(s) with consistent physical characteristics alone or with a suitable excipient(s). Current designs include premetered and device-metered DPIs, all of which rely on various energy sources to create and disperse the aerosol during patient inspiration.

Premetered DPIs contain previously measured amounts of formulation in individual containers (e.g., capsules or blisters) that are inserted into the device before use. Premetered DPIs also may contain premetered dose units as ordered multidose assemblies in the delivery system. Device-metered DPIs have an internal reservoir that contains a sufficient quantity of formulation for multiple doses that are metered by the device itself during actuation by the patient. General quality tests for inhalation powders should include the following (see section IV later in this chapter for more detailed discussions of each test):

Nasal spray drug products typically are water-based liquid formulations applied to the nasal cavity for local and/or systemic effects. They contain therapeutically active ingredient(s) dissolved or suspended in solution or mixtures of excipients in a nonpressurized compact container–closure system. The container–closure system includes an integral spray pump unit that upon activation delivers a spray containing an accurately metered amount of fine mist of droplets of the formulation. Dispersion of the formulation as a spray typically is accomplished by forcing the formulation through the nasal actuator and its orifice. Often, such drug products are multidose device-metered (see Inhalation Spray) presentations in which the dose is metered by the spray pump. Nasal spray drug products also may be designed as premetered presentations. General quality tests for nasal sprays should include the following (see section IV later in this chapter for more detailed discussions of each test):

Nasal solutions are drug products that typically are water-based liquid formulations applied to the nasal cavity for local effect. They may contain drug substance(s) dissolved in solution or mixtures of excipients in a nonpressurized compact container–closure system. The container–closure system includes a delivery system that administers nonmetered amounts of drops or a fine mist of droplets of the formulation. Typically, such drug products are multidose presentations. General quality tests for nasal solution drug products should include the following (see section IV later in this chapter for more detailed discussions of each test):

See chapter 905.

To control the tonicity of the formulation of dosage forms where indicated in General Quality Tests for Inhalation Drug Products, the product should be tested for osmolality with appropriate specifications as described in Osmolality and Osmolarity 785.