A metered-dose inhaler (MDI) is a device that delivers a specific amount of medication to the

lung The lungs are the primary Organ (biology), organs of the respiratory system in many animals, including humans. In mammals and most other tetrapods, two lungs are located near the Vertebral column, backbone on either side of the heart. Their ...

s in the form of a short burst of aerosolized medicine that is usually self-administered by the patient via inhalation. It is the most commonly used delivery system for treating

asthma Asthma is a common long-term inflammatory disease of the airways of the lungs. It is characterized by variable and recurring symptoms, reversible airflow obstruction, and easily triggered bronchospasms. Symptoms include episodes of wh ...

chronic obstructive pulmonary disease Chronic obstructive pulmonary disease (COPD) is a type of progressive lung disease characterized by chronic respiratory symptoms and airflow limitation. GOLD defines COPD as a heterogeneous lung condition characterized by chronic respiratory s ...

(COPD) and other respiratory diseases. The medication in a metered dose inhaler is most commonly a

bronchodilator A bronchodilator or broncholytic (although the latter occasionally includes secretory inhibition as well) is a substance that dilates the bronchi and bronchioles, decreasing resistance in the respiratory airway and increasing airflow to the lun ...

corticosteroid Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones. Two main classes of corticosteroids, glucocorticoids and mineralocorticoids, are invo ...

or a combination of both for treating asthma and COPD. Other medications less commonly used but also administered by MDI are mast cell stabilizers, such as

cromoglicate Cromoglicic acid (INN)—also referred to as cromolyn (USAN), cromoglycate (former BAN), or cromoglicate—is traditionally described as a mast cell stabilizer, and is commonly marketed as the sodium salt sodium cromoglicate or cromolyn sodium. ...

nedocromil Nedocromil sodium is a medication considered a mast cell stabilizer which acts to prevent wheezing, shortness of breath, and other breathing problems caused by asthma. It is administered by an inhaler under the brand name Tilade, and as an eye dr ...

Description

A metered-dose inhaler consists of three major components: the canister, which is produced in aluminum or stainless steel by means of

deep drawing Deep drawing is a sheet metal forming process in which a sheet metal blank is radially drawn into a forming die by the mechanical action of a punch. It is thus a shape transformation process with material retention. The process is considered "dee ...

, where the formulation resides; the metering valve, which allows a metered quantity of the formulation to be dispensed with each actuation; and an actuator (or mouthpiece) which enables the patient to operate the device and directs the aerosol into the patient's lungs. The formulation comprises the drug, a liquefied gas propellant and, in many cases, stabilizing

excipients An excipient is a substance formulated alongside the active ingredient of a medication. They may be used to enhance the active ingredient’s therapeutic properties; to facilitate drug absorption; to reduce viscosity; to enhance solubility; to i ...

. The actuator contains the mating discharge nozzle and generally includes a dust cap to prevent contamination. To use the inhaler, the patient presses down on the top of the canister, with their thumb supporting the lower portion of the actuator. Actuation of the device releases a single metered dose of the formulation, which contains the medication either dissolved or suspended in the propellant. Breakup of the volatile propellant into droplets, followed by rapid evaporation of these droplets, results in the generation of an aerosol consisting of micrometer-sized medication particles that are then inhaled.

Uses

Metered-dose inhalers are only one type of

inhaler An inhaler (puffer, asthma pump or allergy spray) is a medical device used for delivering medicines into the lungs through the work of a person's breathing. This allows medicines to be delivered to and absorbed in the lungs, which provides the ...

, but they are the most commonly used type. The replacement of

chlorofluorocarbons Chlorofluorocarbons (CFCs) and hydrochlorofluorocarbons (HCFCs) are fully or partly halogenated hydrocarbons that contain carbon (C), hydrogen (H), chlorine (Cl), and fluorine (F). They are produced as volatile derivatives of methane, ethane, ...

propellants with

hydrofluoroalkanes Organofluorine chemistry describes the chemistry of organofluorine compounds, organic compounds that contain a carbon–fluorine bond. Organofluorine compounds find diverse applications ranging from oil and water repellents to pharmaceuticals, ...

(HFA) resulted in the redesign of metered-dose inhalers in the 1990s. For one variety of beclomethasone inhalers, this redesign resulted in considerably smaller aerosol particles being produced and increased in potency by a factor of 2.6. * Asthma inhalers contain a

medication Medication (also called medicament, medicine, pharmaceutical drug, medicinal product, medicinal drug or simply drug) is a drug used to medical diagnosis, diagnose, cure, treat, or preventive medicine, prevent disease. Drug therapy (pharmaco ...

that treats the symptoms of asthma. * Nicotine inhalers allow

cigarette A cigarette is a narrow cylinder containing a combustible material, typically tobacco, that is rolled into Rolling paper, thin paper for smoking. The cigarette is ignited at one end, causing it to smolder; the resulting smoke is orally inhale ...

smokers to get

nicotine Nicotine is a natural product, naturally produced alkaloid in the nightshade family of plants (most predominantly in tobacco and ''Duboisia hopwoodii'') and is widely used recreational drug use, recreationally as a stimulant and anxiolytic. As ...

without using

tobacco Tobacco is the common name of several plants in the genus '' Nicotiana'' of the family Solanaceae, and the general term for any product prepared from the cured leaves of these plants. More than 70 species of tobacco are known, but the ...

, much like nicotine gum or a nicotine patch. The US

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respo ...

(FDA) has approved some nicotine inhaler products for

smoking cessation Smoking cessation, usually called quitting smoking or stopping smoking, is the process of discontinuing tobacco smoking. Tobacco smoke contains nicotine, which is Addiction, addictive and can cause Substance dependence, dependence. As a resu ...

. Nicotine inhalers that are marketed as

nicotine replacement therapy Nicotine replacement therapy (NRT) is a medically approved way to treat people with tobacco use disorder by taking nicotine through means other than tobacco. It is used to help with quitting smoking or stopping chewing tobacco. It increases th ...

should not be confused with

electronic cigarette An electronic cigarette (e-cigarette), or vape, is a device that simulates smoking. It consists of an atomizer, a power source such as a battery, and a container such as a cartridge or tank. Instead of smoke, the user inhales vapor. As such ...

s, which produce an aerosol, usually from a tobacco extract, using a heating coil, while nicotine inhalers produce a noncombusted nicotine aerosol. A study found that "levels of carcinogens and toxins in e-cigarettes typically exceeded those measured in an FDA-approved nicotine inhaler." Nicotine inhalers are also known by their nickname of "the puffer." These devices are made of thin plastic, sometimes resembling a cigarette or a cylinder shape. They contain a porous nicotine-filled plug located at the base of the product. When you puff on the inhaler, nicotine aerosol is inhaled and absorbed in the mouth's lining. Every inhaler delivers almost four hundred puffs of this nicotine vapor. The nicotine inhaler is also temperature-sensitive. In cooler weather, less nicotine is delivered. The nicotine inhaler is considered more straightforward to use than the electronic cigarette as it is usually disposable and contains fewer parts than the electronic cigarette. ** Nicotine inhalers also exist as non-MDIs; for example, the format for the Nicorette Inhalator is an "inhalation vapour solution." * ''

Dry powder inhaler A dry-powder inhaler (DPI) is a device that delivers medication to the lungs in the form of a dry powder. DPIs are commonly used to treat respiratory diseases such as asthma, bronchitis, emphysema and Chronic obstructive pulmonary disease, COPD ...

s'' involve micronized powder, often packaged in single-dose quantities in

blisters A blister is a small pocket of body fluid (lymph, Serum (blood), serum, Plasma (blood), plasma, blood, or pus) within the Epidermis, upper layers of the skin, usually caused by forceful rubbing (friction), burning, freezing, chemical exposure o ...

or gel capsules containing the powdered medication to be drawn into the

s by the user's breath. These systems tend to be more expensive than the MDI, and patients with severely compromised lung function, such as those that occur during an asthma attack, may find it difficult to generate enough airflow to get good function from them. * Metered-dose inhalers can be used to treat COPD, both in a stable state and during lung attacks.

History

Before the invention of the MDI, asthma medication was delivered using a fragile and unreliable squeeze bulb

nebulizer In medicine, a nebulizer (American English) or nebuliser (English language, English) is a drug delivery device used to administer medication in the form of a mist inhaled into the lungs. Nebulizers are commonly used for the treatment of asthma, c ...

. The relatively crude nature of these devices also meant that the particles that they generated were relatively large, too large for effective drug delivery to the lungs. Nonetheless, these nebulizers paved the way for inhalation drug delivery, inspiring the MDI. MDIs were first developed in 1955 by Riker Laboratories, now a subsidiary of 3M Healthcare. At that time, MDIs represented a convergence of two relatively new technologies, the CFC propellant and the Meshburg metering valve, originally designed for dispensing perfume. The initial design by Riker used a glass canister coated with vinyl plastic to improve its resilience. By 1956, Riker had developed two MDI-based products, the Medihaler-Ept containing

epinephrine Adrenaline, also known as epinephrine, is a hormone and medication which is involved in regulating visceral functions (e.g., respiration). It appears as a white microcrystalline granule. Adrenaline is normally produced by the adrenal glands a ...

and the Medihaler-Iso containing

Isoprenaline Isoprenaline, also known as isoproterenol and sold under the brand name Isuprel among others, is a sympathomimetic medication which is used in the treatment of acute bradycardia (slow heart rate), heart block, and rarely for asthma, among other ...

. Both products are

agonist An agonist is a chemical that activates a Receptor (biochemistry), receptor to produce a biological response. Receptors are Cell (biology), cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an R ...

s that provide short-term relief from asthma symptoms and have now largely been replaced in asthma treatment by

salbutamol Salbutamol, also known as albuterol and sold under the brand name Ventolin among others, is a medication that opens up the medium and large airways in the lungs. It is a short-acting β2 adrenergic receptor agonist that causes relaxation of ...

, which is more selective.

Spacers

Metered-dose inhalers are sometimes used with add-on devices referred to as holding chambers or spacers, tubes attached to the inhaler that act as a reservoir or holding chamber and reduce the speed at which the aerosol enters the mouth. They serve to hold the medication that is sprayed by the inhaler. This makes it easier to use the inhaler and helps ensure that more of the medication gets into the lungs instead of just into the mouth or the air. Proper use of a spacer can make an inhaler more effective in delivering medicine. Spacers can be especially helpful to adults and children who find a regular metered dose inhaler hard to use. People who use corticosteroid inhalers should use a spacer to prevent getting the medicine in their mouth, where oral yeast infections and

dysphonia A hoarse voice, also known as dysphonia or hoarseness, is when the voice involuntarily sounds breathy, raspy, or strained, or is softer in volume or lower in pitch. A hoarse voice can be associated with a feeling of unease or scratchiness in the ...

can occur.

Lifespan and replacement

The deposition of the content of drug formulation on the canister surface can result in a shorter shelf life of an MDI

. Applying a suitable surface coating to the components helps to extend this shelf life. Over the years, various coating processes have been developed that can be applied to both the canister and valve to protect the contents from deposition and degradation. Gas plasma processing is an industrial technique carried out in a vacuum to coat the entire MDI

. It involves constant or pulsed gas excitation by radio frequency (RF) or the microwave field to produce an energetic plasma. This coating ensures that the drug formulation does not stick to the interior wall of the MD

and results in the patient receiving the prescribed dose of medication, extending the product's shelf-life. A metered dose inhaler contains enough medication for a certain number of actuations (or "puffs") printed on the canister. Even though the inhaler may continue to work beyond that number of uses, the amount of medication delivered may not be correct. It is important to keep track of the number of times an inhaler is used so that it can be replaced after its recommended number of uses. For this reason, several regulatory authorities have requested that manufacturers add a dose counter or dose indicator to the actuator. Several inhalation products are now sold with a dose counter-actuator. Depending on the manufacturer and the product, inhalers are sold as a complete unit or the individual canister as a refill prescription.

Inhaler technique and use

While MDIs are commonly used in the treatment of lung-based disorders, their use requires dexterity to complete the required sequential steps to achieve the application of these devices. Incorrect completion of one or more steps in using an MDI can substantially reduce the delivery of the administered medication and, consequently, its effectiveness and safety. Numerous studies have demonstrated that between 50-100% of patients do not use their inhaler devices correctly, with patients often unaware that they are using their inhaled medication incorrectly. Incorrect inhaler technique has been associated with poorer outcomes. Incorrect maintenance and cleaning of metered dose inhalers is also an issue identified by many users, highlighting the need for clear guidance for patients prescribed MDIs.

Propellants

One of the most crucial components of an MDI is its propellant. The propellant provides the force to generate the aerosol cloud and is also the medium where the active component must be suspended or dissolved. Propellants in MDIs typically make up more than 99% of the delivered dose, so the properties of the propellant dominate more than any other individual factor. This is often overlooked in literature and in industry because so few propellants are used, and their contribution is often taken for granted. Suitable propellants must pass a stringent set of criteria, and they must: * have a boiling point in the range of -100 to +30 °C * have a density of approximately 1.2 to 1.5 g cm⁻³ (approximately that of the drug to be suspended or dissolved) * have a

vapour pressure Vapor pressure or equilibrium vapor pressure is the pressure exerted by a vapor in thermodynamic equilibrium with its condensed phases (solid or liquid) at a given temperature in a closed system. The equilibrium vapor pressure is an indicat ...

of 40 to 80 psig * have no toxicity to the patient * be non-flammable * be able to dissolve common additives (active ingredients should be either fully soluble or fully insoluble)

Chlorofluorocarbons (CFCs)

In the early days of MDIs, the most commonly used propellants were the

CFC-11 Trichlorofluoromethane, also called freon-11, CFC-11, or R-11, is a chlorofluorocarbon (CFC). It is a colorless, faintly ethereal, and sweetish-smelling liquid that boils around room temperature. CFC-11 is a Class 1 ozone-depleting substance w ...

CFC-12 Dichlorodifluoromethane (R-12) is a colorless gas popularly known by the genericized brand name Freon (as Freon-12). It is a chlorofluorocarbon halomethane (CFC) used as a refrigerant and aerosol spray propellant. In compliance with the Montreal ...

and CFC-114. In 2008, the

announced that inhalers using

chlorofluorocarbon Chlorofluorocarbons (CFCs) and hydrochlorofluorocarbons (HCFCs) are fully or partly Halogenation, halogenated hydrocarbons that contain carbon (C), hydrogen (H), chlorine (Cl), and fluorine (F). They are produced as volatility (chemistry), volat ...

s as a propellant, such as

Primatene Mist Epinephrine, also known as adrenaline, is a medication and hormone. As a medication, it is used to treat several conditions, including anaphylaxis, cardiac arrest, asthma, and superficial bleeding. Inhaled epinephrine may be used to improv ...

, could no longer be manufactured or sold as of 2012. This followed from U.S. decision to agree to the 1987

Montreal Protocol The Montreal Protocol on Substances That Deplete the Ozone Layer is an international treaty designed to protect the ozone layer by phasing out the production of numerous substances that are responsible for ozone depletion. It was agreed on 16 ...

on Substances that deplete the ozone layer.

Hydrofluorocarbons

Hydrofluorocarbon Hydrofluorocarbons (HFCs) are synthetic organic compounds that contain fluorine and hydrogen atoms, and are the most common type of organofluorine compounds. Most are gases at room temperature and pressure. They are frequently used in air condit ...

propellants have replaced CFC propellants. Concerns about the use of

hydrofluorocarbon Hydrofluorocarbons (HFCs) are synthetic organic compounds that contain fluorine and hydrogen atoms, and are the most common type of organofluorine compounds. Most are gases at room temperature and pressure. They are frequently used in air condit ...

propellants have, however, since arisen since these compounds are potent

greenhouse gas Greenhouse gases (GHGs) are the gases in the atmosphere that raise the surface temperature of planets such as the Earth. Unlike other gases, greenhouse gases absorb the radiations that a planet emits, resulting in the greenhouse effect. T ...

es; propellants released during the use of a single inhaler result in a greenhouse footprint equivalent to greenhouse gases released during a 180-mile car journey.

Surfactant lipids

Phospholipids Phospholipids are a class of lipids whose molecule has a hydrophilic "head" containing a phosphate group and two hydrophobic "tails" derived from fatty acids, joined by an alcohol residue (usually a glycerol molecule). Marine phospholipids typi ...

are important natural

surfactant Surfactants are chemical compounds that decrease the surface tension or interfacial tension between two liquids, a liquid and a gas, or a liquid and a solid. The word ''surfactant'' is a Blend word, blend of "surface-active agent", coined in ...

lipids. used to enhance penetration and bioavailability. Phospholipids reduce the high

surface tension Surface tension is the tendency of liquid surfaces at rest to shrink into the minimum surface area possible. Surface tension (physics), tension is what allows objects with a higher density than water such as razor blades and insects (e.g. Ge ...

forces at the air-water interface within the

alveoli Alveolus (; pl. alveoli, adj. alveolar) is a general anatomical term for a concave cavity or pit. Uses in anatomy and zoology * Pulmonary alveolus, an air sac in the lungs ** Alveolar cell or pneumocyte ** Alveolar duct ** Alveolar macrophage * M ...

, thereby reducing the pressure needed to expand the lungs. Thus, commercially available formulations of phospholipids have been designed to spread rapidly over an air-aqueous interface, thereby reducing what is otherwise a very high surface tension of water.

Colours

For ease of identification, many MDI's are colour-coded

References

External links

UpToDate Patient Information: Metered dose inhaler techniques in adults

Using a metered-dose inhaler with a spacer: techniques for children, illustrated

Using a metered-dose inhaler without a spacer: techniques for children, illustrated
* {{DEFAULTSORT:Metered-Dose Inhaler Asthma Drug delivery devices Smoking cessation Dosage forms