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Acute safety of the CFC-free propellant HFA-134a from a pressurized metered dose inhaler
D Donnell1, L I Harrison, S Ward
1Medical Department, 3 M Health Care Ltd., Loughborough, UK.
Abstract:
The acute safety of the alternative chlorofluorocarbon-free (CFC-free) propellant HFA-134a from a pressurized metered-dose inhaler (MDI) was assessed in 12 healthy male subjects according to a double-blind, randomized, crossover design. On each of three consecutive days, cumulative doses of 1,2,4,8 and 16 inhalations were administered 30 min apart from one of three MDIs. The three MDIs contained either the HFA-134a CFC-free system without drug (HFA-Placebo), the CFC-free system with salbutamol sulphate (HFA-Salbutamol), or a conventional CFC propellant mixture without drug (CFC-Placebo). Pulmonary function (FEV1, FEF25-75%), cardiovascular performance (heart rate and blood pressure), objective tremor measurements and serum potassium were measured after each incremental dose. Similar responses for pulmonary function, cardiovascular performance, tremor and serum potassium were observed between the HFA-Placebo and CFC-Placebo groups. No statistically significant difference was seen in change from baseline of any parameter between the two propellant systems. The administration of HFA-Salbutamol produced statistically significant dose-related increases in heart rate, systolic blood pressure and tremor and a significant dose-related decrease in serum potassium; these responses were expected based on cumulative doses of active drug. Blood samples for HFA-134a analysis were collected to measure systemic absorption of this propellant. Levels of HFA-134a between 200 and 700 ng.ml-1 were detected in all subjects given the CFC-free system. This study shows that acute inhalation of HFA-134a in a CFC-free system is as safe as a CFC propellant system. Salbutamol sulphate in the CFC-free system can be delivered in a dose-linear fashion, without any noticeable change in the safety profile of active drug.
Insights
The new hydrofluoroalkane-134a (HFA-134a) propellant in metered-dose inhalers (MDIs) is as safe as traditional chlorofluorocarbon (CFC) propellants. This CFC-free MDI system effectively delivers salbutamol without altering the drug's safety profile.
Area of Science:
- Pharmacology
- Respiratory Medicine
- Environmental Health
Background:
- Metered-dose inhalers (MDIs) traditionally use chlorofluorocarbons (CFCs) as propellants.
- CFCs are being phased out due to environmental concerns.
- Hydrofluoroalkane-134a (HFA-134a) is a leading CFC-free alternative propellant.
Purpose of the Study:
- To assess the acute safety of HFA-134a as a propellant in MDIs.
- To compare the safety profile of HFA-134a with CFC propellants.
- To evaluate the delivery and safety of salbutamol sulphate using the HFA-134a propellant system.
Main Methods:
- A double-blind, randomized, crossover study involving 12 healthy male subjects.
- Administration of incremental doses (1, 2, 4, 8, 16 inhalations) of HFA-Placebo, HFA-Salbutamol, or CFC-Placebo MDIs.
- Monitoring of pulmonary function (FEV1, FEF25-75%), cardiovascular parameters, tremor, and serum potassium levels.
Main Results:
- No significant differences in pulmonary function, cardiovascular response, tremor, or serum potassium were observed between HFA-Placebo and CFC-Placebo groups.
- HFA-Salbutamol showed expected dose-related increases in heart rate, blood pressure, and tremor, and a decrease in serum potassium.
- HFA-134a propellant levels were detected in subjects using the CFC-free system, indicating systemic absorption.
Conclusions:
- HFA-134a propellant in MDIs demonstrates acute safety comparable to CFC propellant systems.
- The HFA-134a system allows for dose-linear delivery of salbutamol sulphate.
- The safety profile of salbutamol sulphate remains unchanged when delivered via the HFA-134a CFC-free MDI system.