Metered-dose inhaler

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Metered-dose Inhaler Metered-dose Inhaler.JPG
Metered-dose Inhaler

A metered-dose inhaler (MDI) is a device that delivers a specific amount of medication to the lungs 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, chronic obstructive pulmonary disease (COPD) and other respiratory diseases. The medication in a metered dose inhaler is most commonly a bronchodilator, corticosteroid 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 or nedocromil.

Contents

Description

MDI canister and actuator components from H&T Presspart MDI components.jpg
MDI canister and actuator components from H&T Presspart

A metered-dose inhaler consists of three major components: the canister, which is produced in aluminum or stainless steel by means of deep drawing, 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. [1] , [2] The formulation comprises the drug, a liquefied gas propellant and, in many cases, stabilizing excipients. 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. [3]

Uses

Nicorette Inhalator is a vapour inhalator. Nicorette Inhalator.jpg
Nicorette Inhalator is a vapour inhalator.

Metered-dose inhalers are only one type of inhaler, but they are the most commonly used type. The replacement of chlorofluorocarbons propellants with hydrofluoroalkanes (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. [4]

History

Before the invention of the MDI, asthma medication was delivered using a fragile and unreliable squeeze bulb nebulizer. [7] 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. [2] 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. [7] 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. [8] The initial design by Riker used a glass canister coated with vinyl plastic to improve its resilience. [7] By 1956, Riker had developed two MDI-based products, the Medihaler-Ept containing epinephrine and the Medihaler-Iso containing Isoprenaline. [2] Both products are agonists that provide short-term relief from asthma symptoms and have now largely been replaced in asthma treatment by salbutamol, 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. [9]

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 can occur. [10]

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 inhaler. 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 inhaler. 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 inhaler 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. [11] [12] Incorrect inhaler technique has been associated with poorer outcomes. [12] [13] 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. [14] [15]

Propellants

CFC-free Asthalin HFA inhaler Cipla inhaler.jpg
CFC-free Asthalin HFA inhaler

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, [16] 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:

Chlorofluorocarbons (CFCs)

In the early days of MDIs, the most commonly used propellants were the chlorofluorocarbons CFC-11, CFC-12 and CFC-114.

In 2008, the Food and Drug Administration announced that inhalers using chlorofluorocarbons as a propellant, such as Primatene Mist, could no longer be manufactured or sold as of 2012. [19] This followed from U.S. decision to agree to the 1987 Montreal Protocol on Substances that deplete the ozone layer. [20]

Hydrofluorocarbons

Hydrofluorocarbon propellants have replaced CFC propellants. [21] Concerns about the use of hydrofluorocarbon propellants have, however, since arisen since these compounds are potent greenhouse gases; 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. [22]

Surfactant lipids

Phospholipids are important natural surfactant lipids [23] used to enhance penetration and bioavailability. [24] Phospholipids reduce the high surface tension forces at the air-water interface within the alveoli, 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

NameUseUnited KingdomNew ZealandUnited States
SalbutamolRelieverLight BlueLight Blue (Ventolin, Respigen) Gray (Salair)Bright Red (generics) Light Blue (brand name)
BeclometasoneSteroidBrownBrownLight Green
Seretide (Advair in US)CombinationPurplePurplePurple
FostairCombinationPink

Epinephrine in the United States is brown and beclometasone is light green.

See also

Related Research Articles

<span class="mw-page-title-main">Inhaler spacer</span>

A spacer is a device used to increase the ease of administering aerosolized medication from a metered-dose inhaler (MDI). It adds space in the form of a tube or "chamber" between the mouth and canister of medication. Most spacers have a one-way valve that allows the person to inhale the medication while inhaling and exhaling normally; these are often referred to as valved holding chambers (VHC).

<span class="mw-page-title-main">Salbutamol</span> Medication

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 airway smooth muscle. It is used to treat asthma, including asthma attacks and exercise-induced bronchoconstriction, as well as chronic obstructive pulmonary disease (COPD). It may also be used to treat high blood potassium levels. Salbutamol is usually used with an inhaler or nebulizer, but it is also available in a pill, liquid, and intravenous solution. Onset of action of the inhaled version is typically within 15 minutes and lasts for two to six hours.

<span class="mw-page-title-main">Nebulizer</span> Drug delivery device

In medicine, a nebulizer or nebuliser 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, cystic fibrosis, COPD and other respiratory diseases or disorders. They use oxygen, compressed air or ultrasonic power to break up solutions and suspensions into small aerosol droplets that are inhaled from the mouthpiece of the device. An aerosol is a mixture of gas and solid or liquid particles.

<span class="mw-page-title-main">Ipratropium bromide</span> Type of anticholinergic

Ipratropium bromide, sold under the trade name Atrovent among others, is a type of anticholinergic medication which is applied by different routes: inhaler, nebulizer, or nasal spray, for different reasons.

<span class="mw-page-title-main">Salmeterol</span> Chemical compound

Salmeterol is a long-acting β2 adrenergic receptor agonist (LABA) used in the maintenance and prevention of asthma symptoms and maintenance of chronic obstructive pulmonary disease (COPD) symptoms. Symptoms of bronchospasm include shortness of breath, wheezing, coughing and chest tightness. It is also used to prevent breathing difficulties during exercise.

<span class="mw-page-title-main">Budesonide/formoterol</span> Medication for asthma & chronic obstructive pulmonary disease

Budesonide/formoterol, sold under the brand name Symbicort among others, is a fixed-dose combination medication used in the management of asthma or chronic obstructive pulmonary disease (COPD). It contains budesonide, a steroid and formoterol, a long-acting β2-agonist (LABA). The product monograph does not support its use for sudden worsening or treatment of active bronchospasm. However, a 2020 review of the literature does support such use. It is used by breathing in the medication.

<span class="mw-page-title-main">Formoterol</span> Chemical compound

Formoterol, also known as eformoterol, is a long-acting β2 agonist (LABA) used as a bronchodilator in the management of asthma and chronic obstructive pulmonary disease (COPD). Formoterol has an extended duration of action compared to short-acting β2 agonists such as salbutamol (albuterol), which are effective for 4 h to 6 h. Formoterol has a relatively rapid onset of action compared to other LABAs, and is effective within 2-3 minutes. The 2022 Global Initiative for Asthma report recommends a combination formoterol/inhaled corticosteroid inhaler as both a preventer and reliever treatment for asthma in adults. In children, a short-acting β2 adrenergic agonist is still recommended.

<span class="mw-page-title-main">Inhaler</span> Medical device used to deliver medicines into lungs

An inhaler 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 ability for targeted medical treatment to this specific region of the body, as well as a reduction in the side effects of oral medications. There are a wide variety of inhalers, and they are commonly used to treat numerous medical conditions with asthma and chronic obstructive pulmonary disease (COPD) being among the most notable.

Beta<sub>2</sub>-adrenergic agonist Compounds that bind to and activate adrenergic beta-2 receptors

Beta2-adrenergic agonists, also known as adrenergic β2 receptor agonists, are a class of drugs that act on the β2 adrenergic receptor. Like other β adrenergic agonists, they cause smooth muscle relaxation. β2 adrenergic agonists' effects on smooth muscle cause dilation of bronchial passages, vasodilation in muscle and liver, relaxation of uterine muscle, and release of insulin. They are primarily used to treat asthma and other pulmonary disorders. Bronchodilators are considered an important treatment regime for chronic obstructive pulmonary disease (COPD) and are usually used in combination with short acting medications and long acting medications in a combined inhaler.

<span class="mw-page-title-main">Fluticasone propionate</span> Medication

Fluticasone propionate, sold under the brand names Flovent and Flonase among others, is a steroid medication. When inhaled it is used for the long term management of asthma and COPD. In the nose it is used for hay fever and nasal polyps. It can also be used for mouth ulcers. It works by decreasing inflammation.

Ipratropium bromide/salbutamol, sold under the brand name Combivent among others, is a combination medication used to treat chronic obstructive pulmonary disease (COPD). It contains ipratropium and salbutamol.

<span class="mw-page-title-main">Nedocromil</span> Chemical compound

Nedocromil sodium is a medication considered as 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 drop under the brand name Alocril. The effects of nedocromil versus asthma are gradual rather than fast-acting and it is not indicated for acute respiratory distress compared to fast acting bronchodilators like albuterol or other well-known inhaler medications. Liquid preparations of nedocromil are available in the UK under the name Rapitil for use for allergic eye reactions. Nedocromil sodium has been shown to be effective in alleviating symptoms of allergic conjunctivitis.

<span class="mw-page-title-main">Levosalbutamol</span> Chemical compound

Levosalbutamol, also known as levalbuterol, is a short-acting β2 adrenergic receptor agonist used in the treatment of asthma and chronic obstructive pulmonary disease (COPD). Evidence is inconclusive regarding the efficacy of levosalbutamol versus salbutamol or salbutamol-levosalbutamol combinations, though levosalbutamol is believed to have a better safety profile due to its more selective binding to β2 receptors versus β1.

<span class="mw-page-title-main">Dry-powder inhaler</span> Device that delivers medication to the lungs in the form of a dry powder

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 COPD although DPIs have also been used in the treatment of diabetes mellitus.

<span class="mw-page-title-main">Pirbuterol</span> Chemical compound

Pirbuterol is a short-acting β2 adrenoreceptor agonist with bronchodilating action used in the treatment of asthma, available as a breath-activated metered-dose inhaler.

<span class="mw-page-title-main">Indacaterol</span> Chemical compound

Indacaterol is an ultra-long-acting beta-adrenoceptor agonist developed by Novartis. It needs to be taken only once a day, unlike the related drugs formoterol and salmeterol. It is licensed only for the treatment of chronic obstructive pulmonary disease (COPD). It is delivered as an aerosol formulation through a dry powder inhaler.

Ciclosporin is a cyclic polypeptide that has been used widely as an orally-available immunosuppressant. It was originally used to prevent transplant rejection of solid organs but has also found use as an orally administered agent to treat psoriasis, rheumatoid arthritis, dry eye and other auto-immune related conditions. A variety of pre-clinical and clinical studies have been and are investigating its use to treat lung-related disorders via inhalation.

<span class="mw-page-title-main">Tiotropium bromide</span> Long-acting bronchodilator in the maintenance of COPD and asthma

Tiotropium bromide, sold under the brand name Spiriva among others, is a long-acting bronchodilator used in the management of chronic obstructive pulmonary disease (COPD) and asthma. Specifically it is used during periods of breathing difficulty to prevent them from getting worse, rather than to prevent them from happening. It is used by inhalation through the mouth. Onset typically begins within half an hour and lasts for 24 hours.

Fluticasone furoate/umeclidinium bromide/vilanterol, sold under the brand name Trelegy Ellipta among others, is a fixed-dose combination inhaled medication that is used for the maintenance treatment of chronic obstructive pulmonary disease (COPD). The medications work in different ways: fluticasone furoate is an inhaled corticosteroid (ICS), umeclidinium is a long-acting muscarinic antagonist (LAMA), and vilanterol is a long-acting beta-agonist (LABA).

<span class="mw-page-title-main">Pulmonary drug delivery</span>

Pulmonary drug delivery is a route of administration in which patients use an inhaler to inhale their medications and drugs are absorbed into the bloodstream via the lung mucous membrane. This technique is most commonly used in the treatment of lung diseases, for example, asthma and chronic obstructive pulmonary disease (COPD). Different types of inhalers include metered-dose inhalers (MDI), dry powder inhalers (DPI), soft mist inhalers (SMI) and nebulizers. The rate and efficacy of pulmonary drug delivery are affected by drug particle properties, breathing patterns and respiratory tract geometry.

References

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  2. 1 2 3 Swarbrick, James (2007). Encyclopedia of Pharmaceutical Technology (3rd Illustrated ed.). Informa Health Care. p. 1170. ISBN   978-0-8493-9394-5.
  3. ↑ Finlay, W. H., The Mechanics of Inhaled Pharmaceutical Aerosols: An Introduction, Academic Press, 2001.
  4. ↑ Busse W, Colice G, Hannon S (1998). "CFC-BDP require 2.6 times the dose to achieve equivalent improvement in FEV1 as HFA-BDP". Am J Respir Crit Med. 157: A405.
  5. 1 2 3 Drummond, MB; Upson, D (February 2014). "Electronic cigarettes. Potential harms and benefits". Annals of the American Thoracic Society. 11 (2): 236–42. doi:10.1513/annalsats.201311-391fr. PMC   5469426 . PMID   24575993.
  6. ↑ van Geffen, Wouter H; Douma, W R; Slebos, Dirk Jan; Kerstjens, Huib AM (2016-08-29). "Bronchodilators delivered by nebuliser versus pMDI with spacer or DPI for exacerbations of COPD" (PDF). Cochrane Database of Systematic Reviews. 2016 (8): CD011826. doi:10.1002/14651858.cd011826.pub2. PMC   8487315 . PMID   27569680.
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  8. ↑ Clark, A. R (1995). "Medical Aerosol Inhalers: Past, Present, and Future". Aerosol Science and Technology. 22 (4): 374–391. Bibcode:1995AerST..22..374C. doi: 10.1080/02786829408959755 .
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  11. ↑ Vanderman, Adam J.; Moss, Jason M.; Bailey, Janine C.; Melnyk, S. Dee; Brown, Jamie N. (February 2015). "Inhaler misuse in an older adult population". The Consultant Pharmacist. 30 (2): 92–100. doi:10.4140/TCP.n.2015.92. ISSN   0888-5109. PMID   25695415.
  12. 1 2 Gregoriano, Claudia; Dieterle, Thomas; Breitenstein, Anna-Lisa; Dürr, Selina; Baum, Amanda; Maier, Sabrina; Arnet, Isabelle; Hersberger, Kurt E.; Leuppi, Jörg D. (2018-12-03). "Use and inhalation technique of inhaled medication in patients with asthma and COPD: data from a randomized controlled trial". Respiratory Research. 19 (1): 237. doi: 10.1186/s12931-018-0936-3 . ISSN   1465-993X. PMC   6276152 . PMID   30509268.
  13. ↑ Maricoto, Tiago; Monteiro, Luís; Gama, Jorge M. R.; Correia-de-Sousa, Jaime; Taborda-Barata, Luís (2018-10-06). "Inhaler Technique Education and Exacerbation Risk in Older Adults with Asthma or Chronic Obstructive Pulmonary Disease: A Meta-Analysis". Journal of the American Geriatrics Society. 67 (1): 57–66. doi: 10.1111/jgs.15602 . hdl: 10400.6/9162 . ISSN   1532-5415. PMID   30291745.
  14. ↑ Tay, Ee Tein; Needleman, Joshua P.; Avner, Jeffrey R. (March 2009). "Nebulizer and spacer device maintenance in children with asthma". The Journal of Asthma. 46 (2): 153–155. doi:10.1080/02770900802538244. ISSN   1532-4303. PMID   19253121. S2CID   22194306.
  15. ↑ Caufield, Madeleine (8 November 2019). "How Properly To Clean Your Blue Asthma Inhaler". e-Surgery. Retrieved 2019-12-21.
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  19. ↑ Saundra Young (September 22, 2011). "No more Primatene Mist in the U.S. after this year". The Chart (blog). CNN. Archived from the original on 2011-09-22. Retrieved 2011-09-22.
  20. ↑ "The Montreal Protocol on Substances that Deplete the Ozone Layer" (PDF). United Nations Environment Programme. Archived from the original (PDF) on 2009-02-27.
  21. ↑ "Metered Dose Inhalers (MDIs)". Fluorocarbons. Retrieved 2019-04-09.
  22. ↑ Bodkin, Henry (2019-04-08). "Asthma inhalers as bad for the environment as 180-mile car journey, health chiefs say". The Telegraph. ISSN   0307-1235 . Retrieved 2019-04-09.
  23. ↑ Anti-asthmatic combinations comprising surface active phospholipids
  24. ↑ PHOSPHOLIPID-BASED INHALATION SYSTEM
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