Name: Tetrafluoroethane (HFC)
CAS No: 1,1,1,2-Tetrafluoroethane [811-97-2]
None adopted.
Dymel 134a/P; fluorocarbon 134a; Frigen 134a; Genetron 134a; HFA 134a; HFC 134a; Isceon 134a; Klea 134a; propellant 134a; refrigerant 134a; Solkane 134a; Suva 134a; Zephex 134a.
1,1,1,2-Tetrafluoroethane [811-97-2]
C2H2F4 102.0
Tetrafluoroethane is a hydrofluorocarbon (HFC) or hydrofluoroalkane (HFA) aerosol propellant (contains hydrogen, fluorine, and carbon) as contrasted to a CFC (chlorine, fluorine, and carbon). The lack of chlorine in the molecule and the presence of hydrogen reduce the ozone depletion activity to practically zero. Hence tetrafluoroethane is an alternative to CFCs in the formulation of metereddose inhalers (MDIs).(1–9) It has replaced CFC-12 as a refrigerant and propellant since it has essentially the same vapor pressure. Its very low Kauri-butanol value and solubility parameter indicate that it is not a good solvent for the commonly used surfactants for MDIs. Sorbitan trioleate, sorbitan sesquioleate, oleic acid, and soya lecithin show limited solubility in tetrafluoroethane and the amount of surfactant that actually dissolves may not be sufficient to keep a drug readily dispersed. Up to 10% ethanol may be used to increase its solubility. When tetrafluoroethane (P-134a) is used for pharmaceutical aerosols and MDIs, the pharmaceutical grade must be specified. Industrial grades may not be satisfactory due to their impurity profiles.
Tetrafluoroethane is a liquefied gas and exists as a liquid at room temperature when contained under its own vapor pressure, or as a gas when exposed to room temperature and atmospheric pressure. The liquid is practically odorless and colorless. The gas in high concentrations has a slight etherlike odor. Tetrafluoroethane is noncorrosive, nonirritating, and nonflammable.
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Boiling point 26.58C Density 1.21 g/cm3 for liquid at 258C Flammability Nonflammable Freezing point 1088C Kauri-butanol value 8 Solubility Soluble in ethanol (95%), ether, and 1 in 1294 parts of water at 208C. Specific gravity 1.208 at 258C Vapor density (absolute) 4.466 g/cm3 at standard temperature and pressure. Vapor density (relative) 3.6 (air = 1) at 258C Vapor pressure 662 kPa (96 psia) at 258C Viscosity (dynamic) 0.222 mPa s (0.222 cP) for liquid at 208C; 0.210 mPa s (0.210 cP) for liquid at 258C.
Tetrafluoroethane is a nonreactive and stable material. The liquified gas is stable when used as a propellant and should be stored in a metal cylinder in a cool dry place.
The major incompatibility of tetrafluoroethane is its lack of miscibility with water. Since it has a very low Kauri-butanol value, tetrafluoroethane is considered to be a very poor solvent for most drugs used in MDI formulations. It also shows a low solubility for some of the commonly used MDI surfactants.
Tetrafluoroethane can be prepared by several different routes; however, the following routes of preparation illustrate the methods used: Isomerization/hydrofluorination of 1,1,2-trichloro-1,2,2-trifluoroethane (CFC-113) to 1,1-dichloro-1,2,2,2-tetrafluoroethane (CFC-114a), followed by hydrodechlorination of the latter. Hydrofluorination of trichloroethylene, via 1-chloro-1,1,1- trifluoroethane (HCFC-133a).
Tetrafluoroethane is used as a refrigerant and as a non-CFC propellant in various aerosols including topical pharmaceuticals and MDIs. Tetrafluoroethane is regarded as nontoxic and nonirritating when used as directed. No acute or chronic hazard is present when exposures to the vapor are below the acceptable exposure limit (AEL) of 1000 ppm, 8-hour and 12-hour time weighed average (TWA).(10) In this regard it has the same value as the threshold limit value (TLV) for CFC-12. Inhaling a high concentration of tetrafluoroethane vapors can be harmful and is similar to inhaling vapors of CFC-12. Intentional inhalation of vapors of tetrafluoroethane can be dangerous and may cause death. The same labeling required on CFC aerosols would be required for those containing tetrafluoroethane as a propellant (except for the EPA requirement). See Chlorofluorocarbons, Section 14.
Tetrafluoroethane is usually encountered as a liquefied gas and appropriate precautions for handling should be taken. Eye protection, gloves, and protective clothing are recommended. Tetrafluoroethane should be handled in a well-ventilated environment. The vapors are heavier than air and do not support life; therefore, when cleaning large tanks that have contained the propellant, adequate provisions for oxygen supply in the tanks must be made in order to protect workers cleaning the tanks. Although nonflammable, when heated to decomposition tetrafluoroethane emits toxic fumes. In the UK, the long-term workplace exposure limit (8-hour TWA) for tetrafluoroethane is 4240 mg/m3 (1000 ppm).(11)
Included in the FDA Inactive Ingredients Database (aerosol formulations for inhalation and nasal applications). Included in nonparenteral medicines licensed in the UK.
Difluoroethane; heptafluoropropane.
The use of tetrafluoroethane as a propellant for MDIs has been the subject of numerous patents throughout the world. These patents cover the formulation of MDIs and use of specific surfactants, cosolvents, etc. A US patent claims a self-propelling aerosol formulation that may be free of CFCs and which comprises a medicament, 1,1,1,2-tetrafluoroethane, a surface-active agent, and at least one compound having a higher polarity than 1,1,1,2- tetrafluoroethane.(12) Another patent has been issued by the European Patent Office and has 14 claims, among them a claim that includes tetrafluoroethane, an alcohol (such as ethanol), surfactant, and medicament.(13) The formulator is referred to the patent literature prior to formulating a MDI with tetrafluoroethane as the propellant. The formulation of MDI with this non-CFC propellant is complicated since tetrafluoroethane serves as a replacement for dichlorodifluoromethane or dichlorotetrafluoroethane. The use of an HFC as the propellant also requires a change in manufacturing procedure, which necessitates a redesign of the filling and packaging machinery for a MDI.(14) Currently, there are no pharmacopeial specifications for tetrafluoroethane. However, typical specifications are shown in Table I.
