Metered-dose inhaler design

In the United States, use of CEC propeUants, designated as PropeUants 11, 12, and 114, is strictly limited to specialized medicinal aerosol products such as metered-dose inhalers. The physical properties and chemical names of these propeUents are given in Table 2. 

Data adequacy The key study was well designed and conducted and documented a lack of effects on heart and lung parameters as well as clinical chemistry. Pharmacokinetic data were also collected. The compound was without adverse effects when tested as a component of metered-dose inhalers on patients with COPD. Animal studies covered acute, subchronic, and chronic exposure durations and addressed systemic toxicity as well as neurotoxicity, reproductive and developmental effects, cardiac sensitization, genotoxicity, and carcinogenicity. The values are supported by a study with rats in which no effects were observed during a 4-h exposure to 81,000 ppm. Adjustment of the 81,000 ppm concentration by an interspecies and intraspecies uncertainty factors of 3 each, for a total of 10, results in essentially the same value (8,100 ppm) as that from the human study. ... 

The systemic availability of inhaled budesonide has been measured in 15 healthy volunteers, using an open crossover design. Each subject was given three treatments, intravenous budesonide 0.5 mg, inhaled budesonide (from a metered-dose inhaler with a Nebuhaler) 1 mg (200 micrograms x 5) plus oral charcoal, and inhaled budesonide 1 mg without oral charcoal. The treatment order was randomized. The mean systemic availability of inhaled budesonide compared with intravenous budesonide was 36% with charcoal and 35% without charcoal, indicating that the absorption of budesonide from the gastrointestinal tract did not contribute to its systemic availability. Pulmonary deposition was 36% with charcoal and 34% without. When the inhaler was used incorrectly, that is, the canister was shaken only before the first of the five inhalations, systemic availability fell by 50%. This shows that the performance of each inhaler is very dependent on proper use (16). 

Berry, J., Heimbecher, S., Hart, J. L., and Sequeira, J. (2003), Influence of the metering chamber volume and actuator design on the aerodynamic particle size of a metered dose inhaler, Drug. Dev. Ind. Pharm., 29, 865-876. 

Smyth, H., Brace, G, Barbour, T., Gallion, J., Grove, J., and Hickey, A. J. (2006), Spray pattern analysis for metered dose inhalers Effect of actuator design, Pharm. Res., 23, 1591-1596. 

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. 

Metered dose inhalers (MDIs) are pharmaceutical delivery systems designed for oral or nasal use, which deliver discrete doses of aerosolized medicament to the respiratory tract. The MDI contains the active substance, dissolved or suspended in a liquefied propellant system held in a pressurized container that is sealed with a metering valve. Actuation of the valve discharges a metered dose of medicament as an aerosol spray through an actuator during oral or nasal inhalation. 

Atkins, P.J. Barker, N.P. Mathisen, D. The design and development of inhalation drug delivery systems. In Pharmaceutical Inhalation Pressurised Metered-Dose Inhaler Technology, Hickey, A.J., Ed. Marcel Dekker, Inc. New York, 1992. 

Ganderton D, Lewis D, Davies R, Meakin B, BrambiUa G, Church T. Modulite a means of designing the aerosols generated by pressurized metered dose inhalers. Respir Med 2002 96(Suppl D) S3-8. 

INHALATION DRUG DELIVERY SYSTEM DESIGN—METERED-DOSE INHALERS Introduction... 

A metered-dose inhaler (MDI) is a complex system designed to provide a fine mist of medicament, generally with an aerodynamic particle size of less than 5 microns, for inhalation directly to the airways for the treatment of respiratory diseases such as asthma and COPD. 

Most aerosol delivery systems have surfaces that are designed to collect or disperse particles. Jet nebulizers have spheres, as shown in Fig. 4, or plates placed immediately in front of the jet to collector break up large droplets. Metered-dose inhalers do not traditionally have baffles however, the surface of the actuator collects aerosol particles as they pass through the mouthpiece. Dry powder... 

Riker Laboratories, now 3M Healthcare, invented the pressurised metered dose inhaler (MDI) in 1955 when they combined the atomising power of CFCs and a metering valve design. The great majority of valves still use this basic retention valve principle, and hence pressurised MDIs (pMDIs) are all similar in appearance and operation when used with a standard actuator in the normal press and breathe manner. 

The pressurized metered dose inhaler (pMDI) is a pocket sized, hand-held drug delivery system designed to deliver consistent small doses of medicines directly to the patient s lungs. The essential constituents are the medicine, the propellant, and a storage canister, a metering valve, and an actuator. This chapter is concerned with the propellants. It addresses... 

Basically four different types of commercially available aerosol generation devices exist dry powder inhalers (DPIs), metered-dose inhalers (MDIs), classic jet and ultrasonic nebulisers and a new class of high-performance liquid inhalers. Each of these categories has many different variations of the same basic design and working principle... 

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