Metered-dose inhaler sprays

Pharmaceutical powder aerosols have more stringent requirements placed upon the formulation regarding moisture, particle size, and the valve. For metered-dose inhalers, the dispensed product must be deflvered as a spray having a relatively small (3—6 -lm) particle size so that the particles can be deposited at the proper site in the respiratory system. On the other hand, topical powders must be formulated to minimize the number of particles in the 3—6-p.m range because of the adverse effects on the body if these materials are accidently inhaled. 

Fomulationis) nasal spray 25 mg/metered dose inhaler with 0.25 mg/spray... 

Ipratropium is the most commonly used anticholinergic for treating bronchoconstriction in asthma. It is available as an MDI and solution for nebulization. Ipratropium has an onset of action of approximately 30 minutes and a duration of action of 4 to 8 hours. Care should be taken not to spray the metered-dose inhaler into or allow the nebulized solution to get in the patient s eyes, as it can cause mydriasis and blurred vision. 

Liquid instillation and nebulised aerosols are the most common methods for pulmonary administration to experimental animals [22, 54, 109, 134], The use of pressurised metered dose inhaler (pMDIs) and dry powder inhaler (DPIs) in preclinical studies is limited by the need for formulation development, which often cannot be performed in early drug discovery due to short supply of test materials. A number of alternative techniques for intra-tracheal administration of coarse sprays and powder formulations have been described [9, 15, 21, 36, 71, 80, 99, 138],... 

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... 

Other delivery systems are transdermal patches, metered dose inhalers, nasal sprays, implantable devices, and needle-free injections. A description of needleless injection is given in Exhibit 5.16. 

Aerosol 17 (freon-free), 18 mcg/puff in 200 metered-dose inhaler 0.02% (500 mcg/vial) for nebulization Nasal spray 21, 42 mcg/spray Tiotropium (Spiriva)... 

Inhalation drug products include inhalation aerosols (metered dose inhalers) inhalation solutions, suspensions, and sprays (administered via nebulizers) inhalation powders (dry powder inhalers) and nasal sprays. The CMC and preclinical considerations for inhalation drug products are unique in that these drug products are intended for respiratory tract-compromised patients. This is reflected in the level of concern given to the nature of the packaging components that may come in contact with the dosage form or the patient. 

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.)...

Cyr, T. D., Graham, S. J. Low first-spray drug content in albuterol metered-dose inhalers. Pharm Res 8 658-660 (1991). 

As a nasal spray, flunisolide is effective in allergic rhinitis in clinical use [32-34], and their protective effects in patients with bronchial asthma have also been studied. The efficacy and safety of a new metered-dose inhaler of flunisolide has recently been reported [35]. 

Since the introduction of metered-dose inhalers, nasal solutions have increasingly been formulated as nasal sprays. Initially, aerosol-based systems containing chloro-fluorocarbons were employed however, the Montreal Protocol put an end to this. Thereafter, mechanical pumps or actuators were employed to deliver nasal formulations as sprays. These devices, using actuators, can precisely deliver as little as 25 pL and as much as 200 pL of a formulation. However, various factors must be considered in formulating the spray these include viscosity, particle size, and surface tension, all of which may affect the accuracy of the dose administered. 

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. 

Hochrainer, D., Holz, H., Kreher, C., Scaffidi, L., Spallek, M., and Wachtel, H. (2005), Comparison of the aerosol velocity and spray duration of respimat soft mist inhaler and pressurized metered dose inhalers, /. Aerosol Med., 18,273-282. 

A 62-year-old man requiring a metered-dose inhaler (for the first time) was told to spray the medicine to the throat. He was foimd to have been conscientiously aiming and firing the aerosol to his anterior neck around the thyroid cartilage, four times a day for two weeks (Chiang A A, Lee J C 1994 New England Journal of Medicine 330 1690). 

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. 

Inhalation drug products, also referred to as orally inhaled and nasal drug products (OINDPs including inhalation aerosols and solutions, nasal aerosols and sprays), have a high likelihood of packaging component-dosage form interaction,and therefore have individual USFDA guidance documents. As an example, consider the metered dose inhaler (MDI), shown... 

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. 

Tansey, I.P. The challenges in the development of metered dose inhalation aerosols using ozone-friendly propellants. Spray Technol. Mark. 1994, 7, 26-29. 

Metered Dose Inhaler (MDI) Sprays a fixed dose of medication each time the device s button is pressed... 

Nine percent of the medication sprayed reaches the bronchioles. Using a spacer increases the delivery of medication to the bronchioles to 21%. The spacer is a funnel-like device that attaches to the mouthpiece of the meter dose inhaler. When administering medication using an inhaler ... 

Treatment of Migraine. Many years ago, ergotamine via metered dose inhaler was used successfully to treat migraine headache. I was made aware of this when I first became interested in medical aerosols by a senior professor of medicine who testified to its efficacy. More recently, sumatriptan nasal spray has been shown to provide significant relief of headaches [132]. 

Aerosols, Nasal Sprays, Metered-Dose Inhalers, and Dry Powder Inhalers Monograph. USP 29-NF 24 The United States Pharmacopoeia and The National Formulary The Official Compendia of Standards. Rockville, MD The United States Pharmacopeial Convention, Inc, 2006 2617-2636. 

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