Metered-dose inhaler with spacer devices

S. P. Newman, J. Brown, K. P. Steed, S. J. Reader, and H. Kladders, Lung deposition of fenoterol and flunisolide delivered using a novel device for inhaled medicines Comparison of RESPIMAT with conventional metered-dose inhalers with and without spacer devices, Chest 113 951 (1998). 

How to use a metered dose inhaler with the aid of a spacer device... 

Baroody FM. Anatomy and physiology. In Naclerio RM, Durham SR, Mygind N, eds. Rhinitis Mechanisms and Management. New York Marcel Dekker, 1999 1-22. Berg E. In vitro properties of pressurised metered dose inhalers with and without spacer devices. J Aerosol Med 1995 8 S3-S11. 

The Synchroner is a standard metered-dose inhaler with a convenient integral open-tube spacer that adds little to the size of the MDI. When not in use, the spacer is folded against the main body of the canister holder and is held in place by the dust cap. When the inhaler is used, the dust cap is removed and the spacer with mouthpiece is moved until it is at right angles to the inhaler. The device provides a 10-cm gap between the aerosol canister and the patient s mouth, which slows the aerosol down after it comes out of the MDI. 

Berg E. In vitro properties of pressurized metered dose inhalers with and without spacer devices. J Aerosol Med 1995 8(suppl 3) 3—11. 

The most common adverse effects from inhaled corticosteroids include oropharyngeal candidiasis and hoarse voice. These can be minimized by rinsing the mouth after use and by using a spacer device with metered-dose inhalers. Increased bruising and decreased bone density have also been reported the clinical importance of these effects remains uncertain.1,2,19... 

Newman, S.P., Clark, A.R., Talaee, N., and Clarke, S.W., Pressurized aerosol deposition in the human lung with and without an open spacer device. Thorax, 44 706-710 (1989). Newman, S.P., Clark, A.R., Talaee, N., and Clarke, S.W., Lung deposition of 5 mg Intal from a pressurized metered dose inhaler assessed by radiotracer technique, Int. J. Pharm., 74 203-208 (1991). 

Patients who have difficulty in coordination with inhalers can use a spacer device. These remove the need for coordination between actuation of a pressurised metered dose inhaler and inhalation. The spacer device reduces the velocity of the aerosol and subsequent impaction on the oropharynx. In addition, the device allows more time for evaporation of the propellant so that a larger proportion of the particles can be inhaled and deposited in the lungs. The size of the spacer is important, the larger spacers with a one-way valve (Nebuhaler, Volumatic) being most effective. Spacer devices are particularly useful for patients with poor inhalation technique, for children, for patients requiring higher doses, for nocturnal asthma, and for patients who have poor coordination. 

Asmus, M. J., Liang, J., Coowanitwong, I., and Hochhaus, G. (2004), In vitro performance characteristics of valved holding chamber and spacer devices with a fluticasone metered-dose inhaler, Pharmacotherapy, 24,159-166. 

Metered dose inhaler has been the most popular aerosol delivery device for the treatment of respiratory diseases, which is attributable to its portability and simple operation. Although seemingly easy to use, the MDI is a sophisticated device in design. The drug(s) are suspended or dissolved in a liquefied propellant system, which may also contain excipients such as cosolvents or surfactants. The formulation is kept pressurized in a small canister, sealed with a metering valve. Upon actuation through an actuator, the valve opens and the metered dose is dispensed as an aerosol spray from the expansion and vaporization of the propellant under ambient pressure. The inhalers may be used alone or with spacer devices, the electrostatic issues of which are considered in a later section. The present discussion focuses on the inherent charging of particles produced from MDIs. 

There have been three randomized, double-blind studies in adult asthmatics of the efficacy and safety of a beclomethasone dipropionate-hydrofluoroalkane 134a formulation, equivalent in dose per actuation to the currently marketed beclomethasone dipropionate chlorofluorocarbon products (19-21). Daily doses of beclomethasone dipropionate hydrofluoroalkane 134a 1000 pg over 12 weeks given by metered-dose inhaler (19) or a spacer jet device (20) were equivalent in terms of safety and efficacy compared with beclomethasone dipropionate chlorofluorocarbon 1000 pg. The same was true for doses of 400 pg (21). 

Figure 9.5 A metered dose inhaler attached to a spacer device with a mask.

Different types of spacer device are available for use with metered dose inhalers but all work in basically the same manner. The spacer usually consists of two parts that slot together with a mouthpiece at one end and an opening for an inhaler at the other. There is a one-way valve which ensures that when a dose of the inhaler is expressed into the spacer the drug is stored in what is basically a holding device. This makes it easier to use a metered dose inhaler successfully as the two actions (pressing down on the metered dose inhaler and inhaling the medication) can be separated into two separate events. 

In particular, the propellant-driven metered-dose inhalers release the aerosol cloud at the very high velocity caused by the pressure of the propellant. The open-mouth technique of inhalation [79] helps to slow down the droplets (and to evaporate the volatile excipients). An even more effective solution is to use spacer devices [4,79-87], in which the aerosol cloud can slowed down, the volatile constituents can evaporate, and any large particles will sediment out. Moreover, the patient can then inhale the remaining aerosol under optimal conditions for pulmonary delivery [4,8,56,79], that is, with a slow inspiratory flow rate. 

Metered-dose inhaler (MDI) Canister held inverted Formulation (CFC, HFA, solution, suspension) Actuator cleanliness Addition of a spacer device Inspiratory flow (slow, deep) Breath-holding Coordinating actuation with inhalation Priming and shaking the device... 

Mandelberg A, Chen E, Noviski N, Priel IE. Nebulized wet aerosol treatment in emergency department Is it essential Comparison with large spacer device for metered-dose inhaler. Chest 1997 112 1501-1505. 

Many drugs have been formnlated for use with pressurized metered-dose inhalers (pMDIs) (Table 1). The main market for these devices is in the treatment of asthma, allergic diseases, and chronic obstructive pulmonary disease (COPD), for which approximately 500 million pMDIs are produced each year. Their major selling points are that they are cheap and portable. Despite their huge sales, there is increasing concern that the dose of drug patients with asthma receive will vary considerably due to their inhalational technique and to a lesser extent to the variabihty of dose delivery from the pMDI. It is likely, however, that the popularity of pMDIs will continue due to various modifications and additions that are aimed to help with inhalational technique and improve drug delivery. Examples of these include breath-actuated devices, discussed in this chapter, and spacer devices discussed in a subsequent chapter. 

Konig P. Spacer devices used with metered-dose inhalers— breakthrough or gimmick Chest 1985 88 276-284. 

---