Drug delivery devices metered dose inhalers

Wilkes W, Fink J, Dhand R. Selecting an accessory device with a metered-dose inhaler variable influence of accessory devices on fine particle dose, throat deposition, and drug delivery with asynchronous actuation from a metered-dose inhaler. J Aerosol Med 2001 14(3)251-360. 

Pulmonary deposition efficiency depends on physicochemical characteristics, such as density of the aerosol or dry powder particles [33-35], Generally, particle diameters less than than 5 pm are required for efficient pulmonary delivery [36, 37], Pulmonary deposition also depends on the nature of the delivery device and differs between metered dose inhalers (MDIs). For example, pulmonary deposition expressed as the ratio of pulmonary versus total (pulmonary + oral) absorbed drug, ranged from 15-55% for a number of salbutamol devices and from 66-85% for drugs with lower oral bioavailabilities such as budesonide. 

Delivery devices play a major role in the efficiency of pulmonary delivery, and major advances have been made in the development of new devices in recent years. The most commonly used devices for pulmonary drug delivery include nebulizers, metered-dose inhalers (MDIs) and dry-powder inhalers (DPIs). These de-... 

Most inhalation devices deliver approximately 10% of the administered dose to the lower respiratory tract. A number of devices have been developed to increase lung delivery, and delivery of up to 21% has been reported with a pressurized metered-dose inhaler. Despite these advances, drug delivery via the lung is still inefficient. 

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. 

Peart, J. Magyar, C. Byron, P.R. Aerosol electrostatics— metered dose inhalers (MDIs) reformulation and device design issues. In Respiratory Drug Delivery VT, Dalby, R.N., Byron, P.R., Farr, S.J., Eds. Interpharm Press Buffalo Grove, IL, 1998 227-233. 

Pulmonary delivery of drugs is the administration route of choice in respiratory diseases such as chronic obstructive pulmonary disease and asthma. Different devices are available, including metered-dose inhalers, dry powder inhalers, and nebulizers, and nearly 80% of asthmatic patients worldwide use metered dose inhalers (1). Chlorofluorocarbons have been used as an aerosol propellant in metered-dose inhalers however, they deplete the ozone layer and are being replaced by more environment-friendly propellants, even though the contribution of aerosols of this type to the total global burden of chlorofluorocarbons is less than 0.5%. The first chloro-fluorocarbon-free metered-dose inhaler for asthma treatment was approved by the FDA in 1996 (2) and the European Union has set 2005 as a target date for the withdrawal of all chlorofluorocarbon-based inhalers (1). In the USA, prescriptions for chlorofluorocarbon-free medications rose from 16.4 million in 1996 to 33.8 million in 2000 (2). Most of the chlorofluorocarbon-free medications were steroids for nasal use (27.2 million). However, chlorofluorocarbon-containing medications stiU represented two-thirds of all prescriptions and increased from 63.0 to 67.6 million dispensed (2). 

As with the metered-dose inhalers, some old drugs have been repackaged in new devices. For dry powder inhalers these are not true generics but have a similar impact on the marketplace. Most notable of these in the Clickhaler (Innovata Biomed), which is marketed in Europe, for the delivery of albuterol (salbutamol) and beclomethasone. 

Unlike most other drug delivery systems, those in the respiratory area can have a major influence on physician/patient acceptance. A wide range of devices are available in the three main categories of dry powder inhalers (DPIs) and metered dose inhalers (MDIs), i.e., pressurised aerosols and nebulisers. The preferred type of inhaler varies considerably between countries (e.g., DPIs in Scandinavia and MDIs in the United States), and between patient groups (e.g., nebulisers for paediatrics). 

A spacer, a device that attaches directly to the metered-dose inhaler, should be used because a spacer increases the delivery of the drug to the lungs and decreases deposition of the drug on the oropharyngeal mucosa. 

The most important development in antiasthma drug delivery was the advent of the metered-dose inhaler in 1956, which resulted in a huge increase in the use of antiasthma therapy. Sales of pressurized metered-dose inhalers now run at approximately 500 million per year. However, the introduction of this device was not without problems. This section of the chapter covers the early use of propellants in atomization, the origin of the metered-dose inhaler, and the epidemic of asthma deaths. 

In the United States, federal regulation of aerosol doses varies with devices. The metered-dose inhaler (MDI) utilizes a metering valve that is highly regulated and functionally precise. Nebulizers as drug delivery systems are essentially unregulated. 

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. 

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