Kontny M J, Destefano G, Jager P D, McNamara D P, Turi J S, Van Campen L
Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT 06877.
J Aerosol Med. 1991 Fall;4(3):181-7. doi: 10.1089/jam.1991.4.181.
Reformulation of metered-dose inhalers (MDIs) without the use of chlorofluorocarbon (CFC) propellants presents numerous obstacles because there are no alternative propellants that can serve as immediate replacements for pharmaceutical use. Hydrofluorocarbons (HFCs), hydrochlorofluorocarbons (HCFCs) and hydrocarbons (HCs) are all under consideration as possible alternatives for CFC propellants. However, no single propellant or combination of propellants has been identified with all of the physical-chemical properties of CFCs. Based on their zero ozone depletion potentials, relatively low global warming potentials, non-flammabilities, densities, and vapor pressures, HFA-134a and HFA-227 are the most attractive replacement propellants identified to date. Yet, their use in MDIs will still require: (1) identification of a metering valve with propellant and formulation-compatible gaskets, (2) use of current suspending agents at levels much lower than in present MDIs or identification (and characterization) of new suspending agents, and (3) modification of existing manufacturing technologies. Demonstration of acceptable final product stability, safety and efficacy will be necessary prior to submission to worldwide registration authorities.
在不使用氯氟烃（CFC）推进剂的情况下重新配制定量吸入器（MDI）存在诸多障碍，因为没有可作为药物用途直接替代品的替代推进剂。氢氟烃（HFC）、含氢氯氟烃（HCFC）和碳氢化合物（HC）都在被考虑作为CFC推进剂的可能替代品。然而，尚未确定哪种单一推进剂或推进剂组合具有CFC的所有物理化学性质。基于其零臭氧消耗潜能值、相对较低的全球变暖潜能值、不可燃性、密度和蒸气压，HFA - 134a和HFA - 227是迄今为止确定的最具吸引力的替代推进剂。然而，它们在MDI中的使用仍将需要：（1）识别一种带有与推进剂和配方兼容垫圈的计量阀，（2）以远低于当前MDI中的用量使用现有悬浮剂，或者识别（并表征）新的悬浮剂，以及（3）修改现有制造技术。在提交给全球注册机构之前，必须证明最终产品具有可接受的稳定性、安全性和有效性。
