Pressurized metered-dose inhaler

Do not puncture metered dose inhalers or store them near heat or open flame the contents of such inhalers are under pressure Never throw the container into a fire or incinerator. If an unusual smell or taste is noted with use of the inhaler, discontinue use and contact the primary care provider. 

Donnell, D., L.I.Harrison, S.Ward, N.M.Klinger, B.P.Ekholm, K.M.Cooper, I. Porietis, and J.McEwen. 1995. Acute safety of the CFC-free propellant HFA134a from a pressurized metered dose inhaler. Eur. J. Clin. Pharmacol. 48 473— 477. ... 

Metered-dose inhalation aerosols Delivered dose per actuation, number of metered doses, color, particle-size distribution, loss of propellant, pressure, valve corrosion, spray pattern, and absence of pathogenic microorganisms... 

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). 

Zainudin, B.M.Z., Biddiscombe. M., Tolfree, S.E.J., Short, M., and Spiro, S.G., Comparison of bronchodilator responses and deposition patterns of salbutamol inhaled from a pressurized metered dose inhaler, as a dry powder, and as a nebulized solution, Thorax, 45 469-473 (1990). 

As described in Section 3.3 in more detah, particles in the aerosol cloud should preferably have an aerodynamic diameter between 0.5 and 7.5 pm. Currently three different types of devices are used to generate aerosol clouds for inhalation nebulizers (jet or ultrasonic), (pressurized) metered dose inhalers (pMDIs) and dry powder inhalers (DPIs). The basic function of these three completely different devices is to generate a drug-containing aerosol cloud that contains the highest possible fraction of particles in the desired size range. 

Pressurized metered dose inhalers are still the most frequently used systems and they have proven their value in therapy. However, their application in early phases of biopharmaceuti-cal research and further development of dosage forms seems less convenient, since they require special components including propellants, special containers, metering valves, and controlled filling conditions (pressure-filling or cold-filling). 

Aerosolized medications are available as pressurized or breath-actuated metered-dose inhalers (MDIs), dry powder inhalers (DPIs), and nebulized or wet aerosols. Most inhaled medications currently used are available as metered-dose inhalers (Table 3). For the patient who has difficulty to coordinate activation of a MDI, a spacer improves delivery. Spacers reduce deposition of the drug in the... 

N. Butz, C. Porte, H. Courrier, M.P. Krafft, T.F. Vandamme, Reverse water-in-fluorocarbon emulsions for use in pressurized metered-dose inhalers containing hydrofluor-oalkane propellants, Int. J. Pharm. 238 (2002) 257-269. 

Aerosols can be generated by three main drug delivery systems nebulizers, pressurized metered dose inhaler (pMDI), and dry powder inhaler (DPI). 

Figure 1 Schematic example of a pressurized metered dose inhaler.

Excipients Used in Pressurized Metered Dose Inhalers... 

Gupta A, Stein SW, Myrdal PB. Balancing ethanol cosolvent concentration with product performance in 134a-based pressurized metered dose inhalers. J Aerosol Med 2003 16(2) 167-174. 

Williams RO III, Hu C. Investigation of moisture scavengers in pressurized metered-dose inhalers. STP Pharma Sci 2000 10(3) 243-250. 

Williams RO III, Hu C. Moisture uptake and its influence on pressurized metered-dose inhaler. Pharma Dev Technol 2000 5(2) 153 162. 

Baeckstroem K, Nilsson PG. Measurements of droplet size distributions from metered dose inhalers with different vapor pressures and contents of surfactant. J Aerosol Sci 1988 19(7) 1097-1100. 

Tzou TZ. Density, excess molar volume, and vapor pressure of propellant mixtures in metered-dose inhalers deviation from ideal mixtures. Respir Drug Delivery YI, Int Symp 1998 439-443. 

Smyth HDC, Mejia-Millan EA, Hickey AJ. The effect of ethanol on solvency vapor pressure, and emitted droplet size of solution metered dose inhalers containing HFA 134a. Respir Drug Delivery VIII 2002 2 735-738. 

Williams RO III, Repka M, Liu J. Influence of propellant composition on drug delivery from a pressurized metered-dose inhaler. Drug Dev Ind Phann 1998 24(8) 763-770. 

Williams RO III, Brown J, Liu J. Influence of micronization method on the performance of a suspension triamcinolone acetonide pressurized metered-dose inhaler formulation. Pharm Dev Technol 1999 4(2) 167-179. 

Pressurized metered-dose inhaler (pMDI) propellants... 

Thorsson L, Edsbacker S. Lung deposition of budesonide from a pressurized metered-dose inhaler attached to a spacer. Eur Respir J 1998 12(6) 1340-5. 

Goldberg S, Einot T, Algur N, Schwartz S, Greenberg AC, Picard E, Virgihs D, Kerem E. Adrenal suppression in asthmatic children receiving low-dose inhaled budesonide comparison between dry powder inhaler and pressurized metered-dose inhaler attached to a spacer. Ann Allergy Asthma Immunol 2002 89(6) 566-71. 

Inhalation aerosols have been used for the delivery of drugs to the respiratory system since the mid-1950s. The most common dosage form for inhalation is the metered-dose inhaler (MDI), by which the drug is delivered from a pressurized container using a liquefied gas propellant. Medication delivered via this dosage form has allowed for a quick therapeutic response to the symptoms of asthma, emphysema, and chronic obstructive pulmonary disease (COPD), and has resulted in an improvement in the quality of life for millions of asthma sufferers. 

Figure 4 Schematic production sequence for the manufacture of metered-dose inhalers by pressure filling (1) suspension mixing vessel (2) can cleaner (3) can crimper and filler (4) check weigher (5) can coder and heat tester (6) priming and spray testing (7) labeler (8) feeds for tested cans and actuators. (Courtesy of Ellis Horwood Publishers, Ref. 10.)...

Hallworth, G. W. The formation and evaluation of pressurized metered-dose inhalers. In I. Gandeston, I. Jones, eds. Drug Delivery to the Respiratory Tract. Chichester, UK Ellis Horwood, pp. 87-118 (1987). 

Miller, N. C., Schultz, R. K., Schachtner, W. J. Through-life dose uniformity in pressurized metered dose inhalers. Pharm Res 7(9, suppl.) S-88 (1990). 

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