Inhaler
Inhalers are medical devices ( applicators ) used to generate aerosols or vapors that can be inhaled by patients . In addition to nebulizers, the European Pharmacopoeia divides inhalers into pressurized metered dose inhalers, normal pressure metered dose inhalers and powder inhalers , each of which is used to produce an aerosol. Inhalers are used in particular in the treatment of obstructive airways diseases such as asthma or COPD .
application
With inhalers, patients can absorb active substances into the lungs , which have localized effects there or which quickly enter the bloodstream via the alveoli and have a systemic effect . With local therapy, side effects in the rest of the organism can be reduced and a lower dose is required, since a larger proportion of the dose reaches the site of action than with peroral application. But even if the active ingredient is to get into the bloodstream to have a systemic effect, a lower dose is usually necessary, since the first-pass effect in the liver is bypassed. Due to the large resorption area of the lungs (approx. 70-100 square meters) and the thin epithelial layer , active ingredients get into the body faster and can take effect earlier than with oral administration.
A large number of inhalers are marketed for the local therapy of respiratory diseases . In 2006 Pfizer published Exubera , an insulin inhaler for the systemic therapy of insulin-dependent diabetes , but shortly thereafter withdrew it from the market due to a lack of interest. Since 2014 in the United States with AFREZZA a new Insulininhalator available from man-child.
Types
Pressurized metered dose inhalers
Compressed gas metered dose inhalers (also known as metered dose aerosols ) are applicators in which the drug is in liquid form as a solution , suspension or emulsion . The pharmaceutical form reservoir is under pressure due to propellant gases that are usually liquefied under pressure, such as fluorinated hydrocarbons. When actuated, a defined amount of active ingredient is released as an aerosol through a dosing chamber and a suitable valve. Depending on the size of the droplets, the resulting particles reach the lungs at different depths. Usually a particle size with a mean aerodynamic diameter (MMAD) of 1 to 5 µm is aimed for. Larger particles would be deposited on the throat through impaction. Smaller particles between 0.1 and 1 µm sediment too slowly and are exhaled again. Even smaller particles (<0.1 µm) are well separated by diffusion, but are much more difficult to manufacture. The desired particle size can not only be set through the valve size, the surface tension of the formulation can also influence the droplet size.
Coordinated breathing and operation of the inhaler is a prerequisite for successful inhalation. Patients should inhale deeply but slowly in order to achieve high lung excretion. A spacer helps children and patients who have problems with coordinated inhalation - this is an inhalation aid in the form of a plastic chamber that is connected upstream of the metered dose inhaler. Modern pressurized gas metered dose inhalers, such as the Autohaler or Easi-Breathe , apply the dose automatically as soon as the patient inhales, thereby increasing the success of the therapy.
Storage and disposal
Metered dose aerosols contain problematic ingredients such as highly flammable, explosive and health-endangering gases. The containers pose a risk of explosion at high temperatures. For this reason, the sprays must not be stored above 30 degrees Celsius and must be protected from heat, direct sunlight and frost. These storage conditions for propellant cans are regulated in Section 6 of the Ordinance on Hazardous Substances (GefStoffV).
Due to the limited shelf life, most metered dose inhalers are not completely emptied. Small amounts of the gas or the active ingredient thus remain in the pressurized gas container. Until the propellant gas and active substance have been safely and properly removed, the metered aerosols are classified as hazardous waste and must be classified according to waste code 150110 * (packaging containing residues of hazardous substances or contaminated by hazardous substances) or AS 160504 * (gases in pressure containers containing hazardous substances (including halons)). Proper disposal must therefore not take place via the residual waste bin or the yellow sack, as this is hazardous waste that must be disposed of as hazardous goods by a certified disposal company. Therefore metered dose inhalers should be dispensed in the pharmacy or at a hazardous substance mobile.
Normal pressure metered dose inhalers
In normal pressure metered dose inhalers, the preparation is not under pressure, but is atomized by mechanical energy and nozzles or ultrasound.
Powder inhalers
There is a large number of powder inhalers on the market, which differ in their construction and in their application. The powder to be inhaled is either pre-dosed in single-dose containers, such as capsules, or is measured by a suitable dosing mechanism for each application. In contrast to compressed gas metered dose inhalers, the preparation is not actively nebulized by the applicator, but finely distributed and absorbed by the patient's breathing. This makes these inhalers unsuitable for patients who cannot breathe in forcefully.
Nebulizer
Nebulizers separate fine droplets of liquid from a liquid drug reservoir. This creates an aerosol that the patient can inhale through mouthpieces. There are three known functional principles according to which the nebulizers are classified. With nozzle nebulizers, a strong air flow creates a negative pressure at a nozzle and thus pulls droplets out of a capillary system. Since the droplets are of different sizes, a baffle will hold back droplets that are too large. With ultrasonic nebulizers, ultrasound is generated by means of a vibrating piezo crystal, which is responsible for the creation of the droplets. The higher the frequency chosen, the finer the droplets will be (usually 1–3 MHz). Membrane nebulizers are characterized by a very thin membrane consisting of thousands of microbores that vibrates in the kHz range. Due to these vibrations, each microbore acts as a small pump and produces the finest droplets with a defined MMAD.
The time required for inhalative therapy with nebulizers is greater than with powder or compressed gas metered dose inhalers. However, no special breathing coordination is necessary, so this therapy is particularly popular with children.
Individual evidence
- ↑ a b N. R. Labiris, MB Dolovich: Pulmonary drug delivery. Part II: The role of inhalant delivery devices and drug formulations in therapeutic effectiveness of aerosolized medications . In: British Journal of Clinical Pharmacology . tape 56 , no. 6 , December 1, 2003, ISSN 1365-2125 , p. 600-612 , doi : 10.1046 / j.1365-2125.2003.01893.x , PMID 14616419 , PMC 1884297 (free full text) - ( wiley.com [accessed December 21, 2016]).
- ↑ European Directorate for the Quality of Medicines & HealthCare (Ed.): European Pharmacopoeia 8th Edition . Supplemet 4, 2014.
- ^ Gerhard Scheuch, Martin J. Kohlhaeufl, Peter Brand, Ruediger Siekmeier: Clinical perspectives on pulmonary systemic and macromolecular delivery . In: Advanced Drug Delivery Reviews (= Challenges and Innovations in Effective Pulmonary Systemic and Macromolecular Drug Delivery ). tape 58 , no. 9-10 , October 31, 2006, pp. 996–1008 , doi : 10.1016 / j.addr.2006.07.009 ( sciencedirect.com [accessed December 21, 2016]).
- ↑ NR Labiris, MB Dolovich: Pulmonary drug delivery. Part I: Physiological factors affecting therapeutic effectiveness of aerosolized medications . In: British Journal of Clinical Pharmacology . tape 56 , no. 6 , December 1, 2003, ISSN 1365-2125 , p. 588-599 , doi : 10.1046 / j.1365-2125.2003.01892.x , PMID 14616418 , PMC 1884307 (free full text) - ( wiley.com [accessed December 21, 2016]).
- ↑ GefStoffV - unofficial table of contents. Retrieved March 25, 2019 .
- ↑ Disposal of asthma sprays. In: www.abfallmanager-medizin.de/. Retrieved on March 25, 2019 (German).
- ↑ Publications / communications - Federal / State Working Group on Waste (LAGA). Retrieved March 25, 2019 .
- ↑ Disposal of asthma sprays. In: www.abfallmanager-medizin.de/. Retrieved on March 25, 2019 (German).
