Metered-dose inhaler manufacture

Some physicians recommend epinephrine metered-dose inhalers as an alternative to epinephrine autoinjectors. While a few inhalations might relieve mild or moderate respiratory symptoms, for relief of life-threatening airway obstruction or shock, adults need to inhale 20-30 puffs and children need to inhale 10-20 puffs, which is hard to do [35]. Epinephrine metered-dose inhalers contain chlorofluorocarbon propellants. For environmental reasons, they might not be manufactured in the future. 

Draft Guidance for Industry-Metered Dose Inhaler (MDI) and Dry Powder Inhaler (DPI) Drug Products Chemistry, Manufacturing, and Controls Documentation, Nov. 13, 1998. 

Part IE Specific requirements for manufacture of metered-dose inhalers (MDIs)... 

FDA. Metered dose inhaler (MDI) and dry powder inhaler (DPI) drug products chemistry, manufacturing, and controls documentation. CDER/FDA, 1998. 

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.)...

Changes to manufacturing processes of propellant-based metered-dose inhalers (pMDIs) due to the transition to hydrofluoroalkane- (HFA-) based formu lations from chlorofluorocarbon- (CFC-) based systems are under way. These changes are proceeding concurrently with reformulation efforts of the pMDI systems themselves. In some cases, this may result in changes to the formulation [1],... 

The most significant developments in metered-dose inhaler technology to occur since the early 1990s have been the introduction of hydrofluoroalkane (HFA) systems as alternatives to chlorofluorocarbon (CFC) systems [174]. This has largely been caused by the link between the use of CFC systems and ozone depletion in the upper atmosphere [152,175]. Albuterol and beclomethasone have been reformulated in HFA products, but as yet the CFC products are still subject to an annually renewable medical exemption. The Food and Drug Administration has recently published its position on alternative propellant formulations, which should initiate the phase-out of CFCs [176]. In the meantime, a number of generic CFC products of albuterol have been manufactured. The opportunity for reformulation of products as they come of patent is likely to increase research and development in this area in the near future. New formulation opportunities will also arise from these developments, including solutions [177], micellar [178,179], and microemulsion [180]. 

Annex 10 Manufacture of Pressurised Metered Dose Aerosol Preparations for Inhalation Annex 11 Computerised Systems... 

Manufacture of pressurized metered dose aerosol preparations for inhalation... 

Manufacture of immunological veterinary medical products Manufacture of medicinal gases Manufacture of herbal medicinal products Sampling of starting and packaging materials Manufacture of liquids, creams, and ointments Manufacture of pressurized metered-dose aerosol preparations for inhalation... 

AN3 MANUFACTURE OF PRESSURISED METERED DOSE AEROSOL PREPARATIONS FOR INHALATION... 

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