Propellants Montreal Protocol

In 1976 the United States banned the use of CFCs as aerosol propellants. No further steps were taken until 1987 when the United States and some 50 other countries adopted the Montreal Protocol, specifing a 50% reduction of fully halogenated CFCs by 1999. In 1990, an agreement was reached among 93 nations to accelerate the discontinuation of CFCs and completely eliminate production by the year 2000. The 1990 Clean Air Act Amendments contain a phaseout schedule for CFCs, halons, carbon tetrachloride, and methylchloroform. Such steps should stop the iacrease of CFCs ia the atmosphere but, because of the long lifetimes, CFCs will remain ia the atmosphere for centuries. 

The currently marketed MDIs may look similar to the devices that were first developed by Riker in 1950. However, due to the replacement of the ozone-depleting chlorofluorocarbon (CFC) propellants with HFA propellants, virtually all of the components of the MDI have been altered. In 1987, the Montreal Protocol was drawn up, leading to the eventual phase-out of CFC propellants. MDIs contain-... 

In 1974, Rowland and Molina published their hypothesis that CFCs could lead to the depletion of stratospheric ozone. With confirmation of this theory through subsequent studies, an international agreement, The Montreal Protocol on Substances that Deplete the Ozone Layer, ° was drawn up and set in motion a timetable for the phase-out of both the manufacture and use of CFCs. Although the consumption of CFCs in inhalation products is probably insignificant in ozone depletion, representing approximately 0.4% of the worldwide CFC consumption in 1986, the pharmaceutical industry has been working since 1987 to find alternative propellants with which to replace the CFCs used in MDIs. The establishment... 

Under the terms of the Montreal Protocol, aimed at reducing damage to the ozone layer, the use of chlorofluorocarbons has been prohibited since January 1996. Since difluoroethane does not contain chlorine, there are no environmental controls on the use of this material as a propellant, since it does not deplete the ozone layer and is not a greenhouse gas. 

Raoult s law is important because it allows the calculation of vapour pressure from a knowledge of the composition of the solution. The requirement of the Montreal Protocol in 1989 for the replacement of chlorofluorocarbon (CFG) propellants in pressurised metered-dose inhalers with hydrofluoroalkanes (HFAs), because of the ozone-depleting... 

Concern about the diminishment of stratospheric ozone began more than two decades ago. Molina and Rowland (1974) proposed that the release of CFCs through human activity played a major role in 03 depletion. In 1978, the United States banned the use of CFCs as propellants in aerosol sprays. In 1987, the Montreal Protocol on Substances that Deplete the Ozone Layer was established to halt the production by industrialized countries of most 03-destroying CFCs by 2000. The Montreal Protocol was subsequently amended to change the date to 1996 (Ham, 1993). 

Due to the environmental ramifications of CFG use, the Montreal Protocol was devised, and then ratified in 1989, initiating the phase-out of CFG propellants, including those used in MDIs (Figures la-c). As of 2002, the Montreal Protocol has been ratified by 183 countries (UN Environmental Program, 1996). However, because pharmaceutical inhalers are considered life saving for many asthmatic and COPD patients, they were exempted from the protocol pending availability of suitable alternatives (FDA, 21CFR(2), 2002). 

The Montreal Protocol, mandating the discontinuation of GFG propellants, gave the pharmaceutical industry a chance to reevaluate technical attributes of the MDI system. Due to the different physical characteristics of the propellants, excipients previously used in GFG based systems do not behave the same in HFA propellants and therefore also needed to be reinvestigated. 

The 1987 Montreal protocol (4) initially limited the use of CFC propellants and then banned them by 2009 in the United States (51). In addition, degradation kinetics of therapeutic biomolecules is slower in the solid state than in the liquid state. Combined with bypassing the first-pass effect of hepatic metabolism and drug degradation in the gastrointestinal tract, the lungs have been an attractive route of administration of sensitive biomacromolecules in the solid state. The forces of interaction between particles present barriers to their flow and dispersion. The major forces of interaction are van der Waals, electrostatic, and capillary forces (52). 

Because CFC had many essential functions in all aspects of our daily life (for example refrigerants, foaming agents, or propellants for aerosol cans), subsequent to the Montreal Protocol an intensive search for potential replacements was initiated. CFC replacements so far include hydrofluorocarbons (HFC for example CF3CFH2, marketed as HFC-134a), hydrochlorofluorocarbons (HCFC), and partially fluori-nated ethers (for example CH3OCF3). These substances are much less stable to attack by radicals in the lower atmosphere and thus cannot reach the stratosphere where they would deplete the ozone layer [30]. 

Until the mid-1980s, the MDI was the dominant inhalation dosage form, but the Montreal Protocol lead to greatly increased activity in device development, for both existing drugs and new chemical entities. The propellants for the existing MDIs were chlorofluorocarbons... 

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