Nebulizer
`Nebulizers use a variety of techniques to convert a liquid solution of the drug into a
`fine mist, which again contains a wide range of particle sizes.
`
`From: Nunn's Applied Respiratory Physiology (Eighth Edition), 2017
`
`Related terms:
`
`Inorganic Ions, Dry Powder Inhaler, Chronic Obstructive Pulmonary Disease, Salbu-
`tamol, Sodium Chloride
`
`View all Topics
`
`Treatment Delivery Systems
`Bruce K. Rubin, James B. Fink, in Clinical Asthma, 2008
`
`Jet Nebulizer Maintenance
`
`JNs should be rinsed and air dried between treatments and routinely washed.
`Nebulizers should not be stored between treatments still containing medication,
`as this can be a reservoir for bacteria or fungus. The nebulizer should be routinely
`checked for leaks and cracks. Nebulizer performance tends to degrade over time;
`however the newer ones seem to perform more consistently.
`
`Medication should be placed in the nebulizer cup either in unit doses or kept in the
`refrigerator and discarded once the expiration date is reached. Nebulizers should be
`inhaled generally from an upright position as tilting the nebulizer cups can cause
`spillage, loss of medication, and ineffective nebulization. Nebulization should stop
`once the cup begins to sputter. The fill volume of the cup is particularly important
`for nebulizers that have a large residual volume.
`
`> Read full chapter
`
`Pulmonary Drug Delivery
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`Mohammed Ali, in Handbook of Non-Invasive Drug Delivery Systems, 2010
`
`9.3.3 Nebulizers
`
`Nebulizers have been available since the beginning of the twentieth century. Neb-
`ulization from a drug solution is a common method of medical aerosol generation.
`To deliver a drug by nebulization, the drug must first be dispersed in a liquid (usually
`aqueous) medium. After application of a dispersing force (either a jet of gas or
`ultrasonic waves), the drug particles are contained within the aerosol droplets, which
`are then inhaled. At present all commercially available nebulizers can be categorized
`into two types: (i) jet (or pneumatic) small-volume nebulizers and (ii) ultrasonic
`nebulizers. Jet nebulizers are based on the venturi principle, whereas ultrasonic
`nebulizers use the converse piezoelectric effect to convert alternating current to
`high-frequency acoustic energy (Rau, 2002). The major features of both types of
`nebulizer are duration of treatment at each time of use, particle size distributions
`produced, and aerosol drug output.
`
`The formulation of drug solution is usually designed to optimize drug solubility
`and stability; small changes in formulation may also affect inhaled mass, particle
`size distribution, and treatment time. The differences between nebulizer brands
`probably has a greater impact than differences in formulation (O'Riordan, 2002).
`There are several advantages to jet nebulization, including the fact that effective
`use requires only simple, tidal breathing, and that dose modification and dose
`compounding are possible. Disadvantages include the duration of treatment time
`and equipment size. Design modifications to the constant-output nebulizer have
`resulted in breath-enhanced, open-vent nebulizers such as the Pari LC Plus and the
`dosimetric AeroEclipse. Figure 9.8 shows the design of the primary functional parts
`of a jet nebulizer.
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`Figure 9.8. Design of primary functional parts of a classic jet nebulizer.Courtesy of
`PARI Respiratory Equipment Inc., Midlothian, VA, USA.
`
`The second type, ultrasonic nebulizers, usually generates a higher output rate than
`jet nebulizers; however, the average particle size is larger (Rau, 2002). Ultrasonic
`nebulizers can substantially increase reservoir solution temperature, which is the
`opposite of jet nebulizer cooling. Drug concentration in the reservoir does not
`increase with ultrasonic nebulization as it does with jet nebulization. Although
`ultrasonic nebulizers have the same advantages as jet nebulizers, the former is more
`expensive and fragile than the latter type; in addition, the ultrasonic nebulizer may
`cause drug degradation and may not nebulize suspensions well. It has been shown
`that neither type of nebulizer meets the criteria of an ideal inhaler, which would
`generate efficient and quick dose delivery with reproducibility, cost-effectiveness,
`and no ambient contamination by escaped aerosols during administration (Rau,
`2002). However, the electrostatic charge per mass of the nebulized aerosols is
`negligible, which extensively reduces OPL deposition of drug particles and enhanced
`deposition into the deeper lung (Ali et al., 2008a). Another study showed that
`nebulized terbutaline aerosol, 1.8, 4.6, and 10.3 μm particles, deposited 80%, 60%,
`and 44% of drug respectively in the lung (Clay and Clarke, 1987).
`
`> Read full chapter
`
`Asthma and chronic obstructive pul-
`monary disease
`Derek G. Waller BSc (HONS), DM, MBBS (HONS), FRCP, Anthony P. Sampson MA,
`PhD, FHEA, FBPhS, in Medical Pharmacology and Therapeutics (Fifth Edition), 2018
`
`Nebulisers
`
`Nebulisers are devices used with a facemask or mouthpiece to deliver the drug from
`a reservoir solution. There are two types:
`
`▪
`
`▪
`
`Jet nebulisers use compressed air or oxygen passing through a narrow orifice at
`6–8L/minute to suck drug solution from a reservoir into a feed tube. There are
`fine ligaments in this tube, and the impact of the solution on these ligaments
`generates droplets (Venturi principle). Baffles trap the larger droplets.
`Ultrasonic nebulisers use a piezoelectric crystal vibrating at high frequency to
`create the aerosol, and do not require gas flow. The vibrations are transmitted
`through a buffer to the drug solution and form a fountain of liquid in the
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`nebulisation chamber. Ultrasonic nebulisers produce a more uniform particle
`size than jet nebulisers, but are less widely used due to cost.
`
`Up to 10 times the amount of drug is required in a nebuliser to produce the same
`degree of bronchodilation achieved by a metered-dose inhaler. Drug delivery is more
`efficient via a mouthpiece than via a mask from which drug can be deposited in
`the nasal passages.
`
`> Read full chapter
`
`Therapeutic nanostructures for pul-
`monary drug delivery
`Yousef Javadzadeh, Shadi Yaqoubi, in Nanostructures for Drug Delivery, 2017
`
`6.1 Nebulizer
`
`Nebulizers are classic pulmonary drug delivery devices. Glass nebulizers were
`an innovation of the late 19th century as the first inhaler devices (Labiris and
`Dolovich, 2003). These types of pulmonary drug delivery devices require liquid
`formulations to produce polydispersed particles in the range of an inhalable size.
`There are two main types of nebulizers available: the first and most common type
`is jet nebulizer that works based on changes in air pressure. The liquid formulation
`containing drug particles along with the compressed air within the inhaler chamber
`pass through a very narrow tube and enter a wide area; the increase in the volume
`of compressed air leads to reduction of its pressure and atomizes the liquid into
`micron size droplets. In order to catch large and noninhalable particles there is a
`baffle within the inhaler. Finally, small inhalable particles of drug will be sucked into
`the respiratory track to reach the site of action or the site of systemic absorption.
`
`The other type of nebulizer utilizes ultrasonic power in order to produce mi-
`cron-scaled inhalable particles; ultrasonic nebulizers break down the drug solution
`into small droplets via piezoelectric vibration. There is a baffle within the inhaler, as
`well as jet nebulizers, to remove large droplets and return them to the main chamber
`of device.
`
`> Read full chapter
`
`Humidification and Filtration
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`Benjamin M. Hyers, ... James B. Eisenkraft, in Anesthesia Equipment (Third Edition),
`2021
`
`Nebulizers
`
`Nebulizers work by creating a mist of droplets that are suspended in a gas which can
`be useful for airway hydration and medication delivery. Different types exist such
`as jet, spinning disc, and ultrasonic nebulizers. Jet nebulizers take high pressure
`gas and use a venturi to cause a pressure differential, which draws liquid from the
`reservoir to the gas. This causes the liquid to be broken apart into a spray. Spinning
`disc nebulizers use centrifugal forces to produce microdroplets by drawing water
`onto a rotating disc. Ultrasonic nebulizers use high-frequency vibrations to create a
`mist. The size of the droplets that are created dictate where in the respiratory system
`they will reach. For example, greater than 5-μm droplets are likely to be deposited
`in the main airways, which can increase resistance to flow. Sterile water must always
`be used because these droplets are ideal carriers for microbes.42,43
`
`> Read full chapter
`
`Aerosols and Aerosol Drug Delivery Sys-
`tems
`Beth L. Laube, Myrna B. Dolovich, in Middleton's Allergy (Eighth Edition), 2014
`
`Ultrasonic Nebulizers
`
`Ultrasonic nebulizers incorporate a piezoelectric crystal, which is vibrated at a high
`frequency with sufficient intensity to create standing waves on the surface of the
`liquid overlying the crystal. Droplets are formed that remain within the nebulizer
`until they are swept out by a fan or the patient's inspiratory breath.
`
`Most current ultrasonic nebulizers operate at frequencies above 1MHz, produc-
`ing aerosols with MMADs between 2 and 12µm, with an output that is two to
`three times higher than with most jet nebulizers.41 Heat is produced along with
`the aerosol, however, because the ultrasonic nebulizer solution is sonicated, and
`the temperature can rise 10° to 15°C over a 10-minute treatment period, which
`may adversely affect heat-sensitive components of formulations, such as proteins.
`Ultrasonic nebulizers also are not suitable for nebulizing suspensions.
`
`> Read full chapter
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`Pulmonary Administration of
`Biodegradable Drug Nanocarriers for
`More Efficacious Treatment of Fungal
`Infections in Lungs: Insights Based on
`Recent Findings
`Biswajit Mukherjee, ... Soma Sengupta, in Multifunctional Systems for Combined
`Delivery, Biosensing and Diagnostics, 2017
`
`8.1 Nebulizer
`
`Nebulizers have been used to treat respiratory diseases for many years. The working
`principle of jet nebulizer is based on Bernoulli principle by which compressed gas
`(air or oxygen) is passed through a narrow orifice, creating a low-pressure area
`at the adjacent liquid feed tube (Fig. 14.3). This evacuates the solution, with the
`drug being drawn up from the fluid reservoir and shattered in the gas stream
`through fine droplets. In an ultrasonic nebulizer, a piezoelectric crystal is used with
`a high vibrating frequency (usually 1–3 MHz) to generate a fountain of liquid in the
`mobilizing chamber.
`
`Figure 14.3. Nebulizer and its components.
`
`The physical properties of pulmonary drug formulations may have an outcome based
`on particle size and nebulization rates. The viscosity, osmolarity, ionic strength, pH,
`and surface tension may also affect the nebulization of some formulations.
`
`Constant output jet nebulizer can aerosolize most of the drug solution, and provides
`a large dose with very little patient coordination skill. Treatment by using a nebulizer
`can be time consuming, and also less effective, where there is 50% loss with a
`continuously operated nebulizer. On average, only 10% of the total dose loaded in
`a nebulizer is in reality deposited in the lungs (Giraud and Roche, 2002).
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`Recently, technically advanced novel nebulizers have been developed to reduce drug
`wastage and improve delivery efficacy. In a nebulizer, the aerosol output is
`increased by directing auxiliary air entrained at the time of inspiration by enhanced
`delivery designs. Adaptive aerosol delivery monitors a patient’s breathing pattern in
`the first three breaths, and then targets the aerosol delivery into the first 50% of
`inhalation of each time. This commits that the aerosol is delivered to the patient
`during inspiration only, thereby eliminating loss during expiration that occurs with
`a continuous output nebulizer (Ashurst et al., 2000; Borgstrom et al., 1996).
`
`> Read full chapter
`
`Drug Administration by Inhalation in
`Children
`Angela Mary Fonceca PhD, ... Sunalene Devadason PhD, in Kendig's Disorders of the
`Respiratory Tract in Children (Ninth Edition), 2019
`
`Nebulizers
`
`Nebulizers can be used to deliver a wide range of drugs, in both solution and
`suspension formulation (i.e., a single nebulizer unit can be used to deliver multiple
`drugs). Metered dose inhalers (pressurized and dry powder), on the other hand, are
`specific for a drug-device combination and involve a high cost during the R&D phase
`and, in the postdevelopment phase, testing is required to obtain regulatory approval.
`Hence, aerosolized drugs for diseases such as cystic fibrosis are most often delivered
`via nebulizer.
`
`However, it is now recognized that because of the large variability in delivery from
`different nebulizer types, safety and efficacy testing (particularly of new drugs)
`needs to take into account the specific drug-nebulizer combination being used. For
`example, the product literature for Pulmozyme (dornase alpha) includes a list of
`recommended nebulizers, and specifies the compressors to be used with each of
`the recommended jet nebulizers.
`
`Nebulizers may not be ideal devices to generate a therapeutically effective aerosol
`from a novel drug formulation. This could lead to overdosing or underdosing of
`the lung as nebulizer performance can vary widely when used to aerosolize a drug
`either not intended to be delivered in an aerosolized form, or designed to be used
`in a different nebulizer. Off-label use of drug and/or delivery devices with a failure
`to match the drug to the delivery device can lead to problems.
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`Drugs such as antibiotics (tobramycin) used in the treatment of Pseudomonas spp.
`lung infections have comparatively high MICs and the large volumes required to
`achieve a therapeutic concentration at the site of action preclude their use as a pMDI
`formulation. More potent drugs such as those used in the treatment of asthma
`require far less total dose; hence the widespread use of pMDI formulations for
`asthma. Thus nebulizers generating a “wet” aerosol are the device of choice for many
`drugs.76
`
`Jet nebulizers have been used for many years for the treatment of respiratory disease
`(Fig. 16.6). Drug formulations for jet nebulizers are generally aqueous solutions,
`although some drugs are dispensed in the form of suspensions (corticosteroids) or
`viscous solutions (antibiotics). The simplest of the nebulizer designs is the T-piece jet
`nebulizer (Fig. 16.7). An aerosol is generated by passing air flow through a Venturi in
`the nebulizer bowl. This forms a low-pressure zone that pulls up droplets through a
`feed tube from a solution or suspension of drug in the nebulizer bowl, and in turn
`this creates a stream of atomized droplets, which flow to the mouthpiece. Higher
`air flows lead to a decrease in particle size and an increase in output. A baffle in
`the nebulizer bowl is impacted by larger particles, retaining them and returning
`them to the solution in the nebulizer bowl to be reatomized. There is considerable
`variation in the performance of nebulizers.77 In addition, nebulizers require a source
`of compressed air, which make them bulkier and more inconvenient to use than
`other inhalation systems.
`
`Another solution to increase total drug delivery and improve deposition was the
`storage of aerosol generated during expiration in a holding chamber.73,78,79 These
`solutions proved inconvenient for widespread use, increasing nebulization times
`and making the delivery systems even more bulky and cumbersome.
`
`Entrainment of air through the nebulizer bowl as the patient inhales has been shown
`to increase aerosol output during inspiration.80 The development of nebulizers
`utilizing this principle (entrainment or breath-enhanced nebulizers) (Fig. 16.8) have
`been shown to result in increased deposition.81 These “entrainment” jet nebulizers
`are now commonly used for long-term delivery of aerosol medications for diseases
`such as cystic fibrosis (see Fig. 16.6). Fig. 16.9 shows the increase in colistin delivery
`resulting from the use of an entrainment nebulizer compared with a standard
`T-piece jet nebulizer.
`
`The duration of nebulization ranges from 5 to 20 minutes, depending on the type of
`nebulizer and the volume of drug formulation in the nebulizer bowl.82 Generation of
`an aerosol with a smaller particle size distribution is desirable, but using a nebulizer
`designed to do this can result in an increased nebulization time. Tapping the
`nebulizer bowl during nebulization results in increased total drug output as larger
`droplets deposited on the walls of the bowl are shaken back into the main volume of
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`drug solution, but this also increases the nebulization times.83 The “dead volume”
`of jet nebulizers containing the residual drug solution that cannot be nebulized also
`results in wastage of drug. Any evaporation of the solution in the nebulizer bowl
`during nebulization means that the concentration of drug in the dead volume is
`higher than that in the aerosol generated.83 If saline is used to dilute the nebulization
`solution, drug wastage can be reduced at the expense of increased nebulization
`times.
`
`Children usually inhale the aerosols generated by these nebulizers using tidal
`breathing, although some reports suggest that deep inspirations, either with or
`without breath holding, would give better results.84–86 Administration via a face mask
`that allows nasal inhalation, or a nasal mask, has been shown to greatly reduce lung
`deposition,87 since the nose is much more efficient than the mouth in filtering out
`any particles with a diameter greater than 1µm.
`
`A further development in nebulizer technology is the vibrating mesh nebulizer, also
`now commonly used for long-term nebulizer therapy. These were developed in the
`early 2000s. In these devices the vibration of a piezoelectric crystal is not used directly
`to generate the aerosol, but rather used to vibrate a thin metal plate perforated by
`several thousand laser-drilled holes (Fig. 16.10). One side of the plate is in contact
`with the liquid to be aerosolized, and the vibration forces this liquid through the
`holes, generating a mist of tiny droplets. By altering the pore size of the mesh, the
`device can be tailored for use with drug solutions of different viscosities, and the
`output rate changed. Mesh nebulizers are powered either by mains electricity or by
`battery, are more portable than jet nebulizers, and they are silent in operation, in
`contrast to the rather noisy compressors used to drive jet nebulizers. Output rate is
`higher than that attained by a jet nebulizer, and a higher dose can be attained in a
`short time.88
`
`Nebulizers can also be used to provide feedback to the patient to indicate when
`correct use has been achieved and to reinforce optimal inhalation technique. The
`I-neb (Respironics) operating in targeted inhalation mode provides audible and
`tactile feedback that informs the patient when the dose has been correctly delivered,
`thereby improving adherence.89
`
`Refinements of standard jet and vibrating mesh nebulizers are aimed at both
`increasing lung deposition rates of drug, and reducing waste of the drug during ex-
`piration, as conventionally, the aerosol is continuously generated. This is important
`when treating children, as compliance with instructions on how to breathe can be
`reinforced by active feedback from the device being used. Breath activated nebulizers
`detect the patient's inspiratory flow and only release aerosol when the flow is suf-
`ficient to open a valve (AeroEclipse, Trudell Medical International, Ontario, Canada).
`Breath-controlled nebulizer compressors, such as the Akita (Activaero, Gemunden,
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`Germany), monitor the child's breathing pattern and only generate aerosol during
`the phase of the respiratory cycle when inspiratory flows are conducive to drawing
`the aerosol into the lungs (Fig. 16.11). The duration of the inspiratory flow on
`triggering can be set, to encourage slow and deep breathing by feedback from the
`device.90 A refinement of this is adaptive aerosol delivery, where the device such as
`the I-neb (Respironics) “learns” the child's breathing pattern and tailors the release
`of the dose to match the individual breathing pattern.91 These enhancements of
`the aerosol delivery process decrease the wastage of drug, which is increasingly
`important with expensive new peptide and recombinant protein drugs, as well as
`improving targeting of the inhaled drug to the site of action, by only introducing
`aerosol into the inhaled air flow when the flow rate is optimal to target the desired
`region of the lung region with the particle size being generated.
`
`Ultrasonic nebulizers generate aerosols using the vibration of a piezoelectric crystal,
`which is transferred to the drug solution. The solution breaks up into droplets at the
`surface, and the resulting aerosol drawn out of the device by the patient's inhalation,
`or pushed out by an air flow through the device generated by a small compressor.92
`Ultrasonic nebulizers are not suitable for suspensions (corticosteroids) or viscous
`solutions (antibiotics) since very little drug is carried in the aerosolized particles,80
`and hence they have a more limited application than mesh nebulizers. Droplet sizes
`tend to be larger with ultrasonic nebulizers than with jet nebulizers.
`
`Small volume liquid inhalers such as the Respimat (Boehringer Ingelheim, Ingel-
`heim, Germany) are devices that use a spring to provide the energy to nebulize
`a small-metered volume of liquid, analogous to the metered dose produced by
`actuation of a pMDI. The energy in the spring is used to push a small volume of drug
`solution through a Venturi, generating a soft wet aerosol plume of about one second
`duration. The slow generation decreases the requirement for accurate coordination
`of actuation and inhalation, making it easier to use than a pMDI. Efficiency of drug
`delivery to the lungs is high, up to 40% of the nominal dose. However, the volume
`of liquid nebulized is only 15µl, making it only suitable for drugs with high potency
`and low dosage mass.93
`
`> Read full chapter
`
`Preparation of the Patient for Awake In-
`tubation
`Carlos A. Artime, Antonio Sanchez, in Benumof and Hagberg's Airway Management,
`2013
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`2 Nebulizers
`
`Nebulizers may be used to apply local anesthetic to the airway. The advantages of this
`technique include ease of application and safety. A standard mouthpiece-type nebu-
`lizer (Fig. 11-4) can topicalize the oropharynx and trachea. If nasal cavity anesthesia is
`needed, a facemask-type nebulizer (Fig. 11-5) can be used; the patient is instructed
`to breathe in through the nose. This approach is especially advantageous for pa-
`tients with increased intracranial pressure (ICP), open eye injury, or severe coronary
`artery disease.118 Foster and Hurewitz compared the administration of lidocaine
`using two different modalities (nebulizer-atomizer combination and atomizer alone)
`in patients undergoing bronchoscopy.119 They found that the nebulizer-atomizer
`combination was more efficacious, resulting in a reduction of the dose required to
`anesthetize the upper airway. A typical dose of lidocaine used in a standard nebulizer
`is 4 mL of 4% lidocaine. This results in a total dose of 160 mg of lidocaine, which is
`well within the safe dosage range. Studies using 6 mg/kg of 10% lidocaine showed
`that peak plasma concentrations are much lower than would be expected if all the
`lidocaine had been absorbed—evidence that some of the local anesthetic is lost
`during exhalation.105
`
`> Read full chapter
`
`Pulmonary Delivery of Peptides and
`Proteins
`Philip Chi Lip Kwok, Hak-Kim Chan, in Peptide and Protein Delivery, 2011
`
`2.4.1 Nebulizers and the AERx® Pulmonary Delivery System
`
`Nebulizers produce droplets from a bulk liquid using either compressed air (jet
`nebulizers) or ultrasonic waves (ultrasonic nebulizers). They generate continuous
`aerosol streams over a period of minutes, thus their aerosol output is much higher
`than those from dry powder inhalers and metered dose inhalers (see below). In
`jet nebulizers, compressed air is forced through a small hole or series of holes on
`the tip of a tube protruding upwards from the liquid reservoir [49]. This creates
`a low pressure zone at the tip of the tube. Consequently, liquid is drawn up the
`tube by the Venturi effect, and is then rapidly dispersed as droplets by the air jet
`[49]. Large droplets impact on a baffle inside the nebulizer and flow back into the
`reservoir. Smaller droplets exit through the mouthpiece for inhalation. The droplet
`size depends on the nebulizer construction and air pressure but generally ranges
`from 2–5 μm. The liquid cools and concentrates during operation due to evaporation
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`in the air jet. Some examples of commercial jet nebulizers are shown in Figure
`2.1. Ultrasonic nebulizers have a piezoelectric crystal below the liquid reservoir. The
`crystal vibrates rapidly to generate ultrasonic waves through the liquid to produce
`droplets for inhalation [50]. The piezoelectric energy input increases the liquid
`temperature during use and may affect the stability of the protein [51].
`
`Figure 2.1. Commercial jet nebulizers: (A) Pari IS-2®; (B) Pari LC® Plus and (C)
`Sidestream®. Pari LC® Plus is recommended for the administration of Pulmozyme®.
`
`Protein nebulizer formulations are mainly aqueous solutions and are relatively
`easy to develop. The factors that may affect their stability are similar to those
`for general protein liquid formulations, such as ionic strength, pH and the type
`and concentration of other dissolved compounds [52]. However, there are some
`potential problems that are unique to nebulizers. Atomizing air pressure, shear,
`recirculation and progressive reduction of solution volume in jet nebulizers may
`lead to protein degradation [53]. Formulations without suitable protein stabilizers
`may also be subject to molecular adsorption to plastic surfaces [53]. The degradation
`rate of nebulized lactate dehydrogenase was found to increase with air pressure,
`nebulization time and low starting solution volumes [54]. The aggregation rate of
`rhG-CSF also increased with nebulization time. However, these adverse effects were
`significantly reduced by the addition of polyethylene glycol (PEG) 1000 in the
`formulation [54]. In another study, the stability of nebulized aviscumine, a dimeric
`protein, was improved by adding various surfactants, cryoprotectants and buffer salts
`to the reconstitution medium [55–57].
`
`High energy vibrations and heat generated in ultrasonic nebulizers may denature
`proteins, as was observed on rhDNase [51]. Therefore, the only jet nebulizers so
`far approved are for the administration of Pulmozyme® [58]. The formulation of
`Pulmozyme® is very simple, with only sodium chloride, calcium chloride dihydrate
`and water for injection as excipients [58,59], illustrating that not all protein nebu-
`lizer formulations require complex additives for stabilization. Thus the stability of
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`

`the protein of interest should be assessed on a case-by-case basis and excipients
`employed where appropriate.
`
`The AERx® pulmonary delivery system devised by Aradigm (California, USA) gen-
`erates aerosols by mechanically extruding the liquid from a unit-dose reservoir
`through micron-sized orifices [60]. Precise delivery control is achieved by internal
`mechanical components that trigger the extrusion mechanism upon inhalation by
`the patient. This device has been successfully used for the delivery of a number of
`proteins, including rhDNase [61], insulin [62,63] and interleukin-4 receptor [64].
`
`> Read full chapter
`
`ScienceDirect is Elsevier’s leading information solution for researchers.
`Copyright © 2018 Elsevier B.V. or its licensors or contributors. ScienceDirect ® is a registered trademark of Elsevier B.V. Terms and conditions apply.
`
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