Hydrofluoroalkane in inhalers

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Hydrofluoroalkane Propellants in Inhalers: Safety, Efficacy, and Environmental Impact

Transition from Chlorofluorocarbon (CFC) to Hydrofluoroalkane (HFA) Propellants

Hydrofluoroalkanes (HFAs) were introduced as propellants in pressurized metered-dose inhalers (pMDIs) to replace chlorofluorocarbons (CFCs), which were phased out due to their harmful effects on the ozone layer 12456. HFAs, such as HFA-134a and HFA-227ea, have become the standard in inhaler formulations for asthma and chronic obstructive pulmonary disease (COPD) 34. The transition required significant redevelopment to ensure that HFA-based inhalers matched the safety, quality, and efficacy of their CFC-based predecessors .

Efficacy and Pulmonary Deposition of HFA Inhalers

Clinical studies have shown that HFA-propelled inhalers are effective in delivering bronchodilators and inhaled corticosteroids, with pulmonary deposition rates typically ranging from 50% to 60% 12. HFA formulations, such as QVAR (HFA-beclomethasone dipropionate), produce smaller aerosol particles compared to CFC formulations, leading to better lung deposition, especially in the small airways, and allowing for lower effective doses . Similar findings were observed with fluticasone and budesonide HFA inhalers, which demonstrated equivalent or improved lung deposition and clinical efficacy compared to their CFC counterparts 679.

Safety Profile of HFA Inhalers

Multiple studies confirm that HFA inhalers are as safe as CFC inhalers. There were no significant differences in hospital admissions or adverse events between patients using HFA and CFC inhalers 1278. Systemic exposure and side effects, such as adrenal suppression, were comparable or even lower with HFA inhalers, supporting their safety for long-term use in adults 579. However, data on the use of HFA inhalers in children and adolescents remain limited, highlighting the need for further research in these age groups 12.

Environmental Considerations and New Developments

While HFAs do not harm the ozone layer, they still contribute to global warming. This has led to the development of new low global warming potential (LGWP) propellants, such as HFA-152a, which offer similar aerodynamic performance and clinical efficacy as current HFA propellants but with a reduced environmental impact . Innovative drug development approaches, including in silico modeling and advanced in vitro testing, have validated the equivalence of these new propellants in delivering medication effectively .

Pharmaceutical Innovations and Drug Delivery

HFA propellants have enabled the development of advanced drug delivery systems, such as reverse water-in-fluorocarbon emulsions, which can efficiently deliver drugs to the lungs using CFC-free pMDIs . These innovations further improve the targeting and effectiveness of inhaled therapies for respiratory diseases.

Conclusion

Hydrofluoroalkane propellants have successfully replaced CFCs in inhalers, providing safe, effective, and environmentally friendlier options for asthma and COPD treatment. HFA inhalers offer improved lung deposition and comparable safety profiles to CFC inhalers, with ongoing advancements aimed at reducing their environmental impact even further. Continued research, especially in pediatric populations and with new LGWP propellants, will ensure that inhaler therapies remain both effective and sustainable 12345678+2 MORE.

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Most relevant research papers on this topic

[Hydrofluoroalkane as a propellant for pressurized metered-dose inhalers: history, pulmonary deposition, pharmacokinetics, efficacy and safety].

Hydrofluoralkane is a safe and effective propellant for pressurized metered-dose inhalers containing anti-asthma drugs, with better pulmonary deposition than chlorofluorcarbon, but more research is needed on its use in children and adolescents.

Systematic Review

2004·

7citations

·C. Ibiapina et al.

Hidrofluoralcano como propelente dos aerossóis pressurizados de dose medida: histórico, deposição pulmonar, farmacocinética, eficácia e segurança

Hydrofluoralkane is a safe and effective propellant for pressurized metered-dose inhalers containing anti-asthma drugs, with better pulmonary deposition and lower annual cost compared to clorofluorcarbon.

Systematic Review

2004·

8citations

·C. Ibiapina et al.

Innovative Drug Development Approach to Address the Transition to Low Global Warming Potential Propellant Using Hydrofluoroalkane-152a, for Triple Combination Pressurized Metered-Dose Inhaler Products Targeting Small Airways.

This study demonstrates that pressurized metered-dose inhalers using low global warming potential HFA-152a can achieve equivalent performance to those using HFA-134a, proving the hypothesis that greener inhalers can be equally effective.

2025·

0citations

·A. Matturro et al.

Transition to CFC-free metered dose inhalers--into the new millennium.

The transition to CFC-free metered dose inhalers is underway, with hydrofluoroalkanes as suitable alternatives for propellants, despite their contribution to global warming.

Highly Cited

2000·

104citations

·K. Mcdonald et al.

Efficacy and safety overview of a new inhaled corticosteroid, QVAR (hydrofluoroalkane-beclomethasone extrafine inhalation aerosol), in asthma.

QVAR is a new inhaled corticosteroid that provides effective asthma control with half the dose needed for CFC-BDP, with low side effects and no more adrenal suppression than CFC-BDP.

Non-RCTHighly Cited

2000·

154citations

·Jennifer A. Vanden Burgt et al.

Fluticasone propionate hydrofluoroalkane inhalation aerosol in patients receiving inhaled corticosteroids.

Fluticasone propionate hydrofluoroalkane inhalation aerosol is an effective and well-tolerated alternative to chlorofluorocarbon-containing inhaled corticosteroids for asthma patients.

RCT

2006·

10citations

·W. Lumry et al.

Pharmacokinetic and pharmacodynamic comparison of hydrofluoroalkane and chlorofluorocarbon formulations of budesonide.

Hydrofluoroalkane and chlorofluorocarbon formulations of budesonide are therapeutically equivalent in terms of lung bioavailability, airway efficacy, and systemic effects.

RCTRigorous Journal

2011·

27citations

·K. Clearie et al.

Postmarketing surveillance study of a non-chlorofluorocarbon inhaler according to the safety assessment of marketed medicines guidelines

The hydrofluoroalkane inhaler is as safe as the chlorofluorocarbon inhaler, but more patients withdrew due to adverse events.

1998·

18citations

·J. Ayres et al.

From hydrofluoroalkane pressurized metered dose inhalers (pMDIs) and comparability with chlorofluorocarbon pMDIs.

Fluticasone propionate HFA 134a pMDIs are an acceptable alternative to current CFC pMDIs, producing similar lung deposition and no increase in systemic exposure at microgram equivalent doses.

RCT

2000·

31citations

·R. Kunka et al.

Reverse water-in-fluorocarbon emulsions for use in pressurized metered-dose inhalers containing hydrofluoroalkane propellants.

Reverse water-in-fluorocarbon emulsions can effectively deliver drugs like cafeine through pulmonary administration using pressurized metered-dose inhalers, with best results achieved with emulsion/propellant ratios between 2/3 and 3/2.

2002·

45citations

·N. Butz et al.

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