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Review

Metered dose inhalers in the transition to low GWP propellants: what we know and what is missing to make it happen

ORCID Icon, ORCID Icon, ORCID Icon &
Pages 1131-1143 | Received 07 Jul 2023, Accepted 25 Sep 2023, Published online: 09 Oct 2023

References

  • Stein SW, Thiel CG. The history of therapeutic aerosols: a chronological review. J Aerosol Med Pulm Drug Deliv. 2017;30(1):20–41. doi: 10.1089/jamp.2016.1297
  • Myrdal PB, Sheth P, Stein SW. Advances in metered dose inhaler technology: formulation development. AAPS Pharm Sci Tech. 2014 Apr;15(2):434–455. doi: 10.1208/s12249-013-0063-x
  • Cataldo D, Hanon S, Peché RV, et al. How to choose the right inhaler using a patient-centric approach? Adv Ther. 2022 Mar;39(3):1149–1163. doi: 10.1007/s12325-021-02034-9
  • U. Environmental Protection Agency. Market characterization of the U.S. Metered dose inhaler industry. no. September. 2021. https://www.epa.gov/sites/default/files/2021-03/documents/epa-hq-oar-2021-0044-0002_attachment_1-mdis.pdf
  • European Environment Agency, Fluorinated greenhouse gases 2020. no. 15. 2020. Available from: https://eea.europa.eu
  • Pernigotti D, Stonham C, Panigone S, et al. Reducing carbon footprint of inhalers: analysis of climate and clinical implications of different scenarios in five European countries. BMJ Open Respir Res. 2021;8(1):1–11. doi: 10.1136/bmjresp-2021-001071
  • NICE. Asthma inhalers and climate change: what is this decision aid about ? 2022. https://www.nice.org.uk/guidance/ng80/resources/inhalers-for-asthma-patient-decision-aid-pdf-6727144573
  • Usmani OS, Scullion J, Keeley D. Our planet or our patients—is the sky the limit for inhaler choice? Lancet Respir Med. 2019;7(1):11–13. doi: 10.1016/S2213-2600(18)30497-1
  • Price D, Roche N, Christian Virchow J, et al. Device type and real-world effectiveness of asthma combination therapy: an observational study. Respir med. 2011;105(10):1457–1466. doi: 10.1016/j.rmed.2011.04.010
  • Woodcock A, Janson C, Rees J, et al. Effects of switching from a metered dose inhaler to a dry powder inhaler on climate emissions and asthma control: post-hoc analysis. Thorax. 2022;77(12):1187–1192. doi: 10.1136/thoraxjnl-2021-218088
  • Pritchard JN. The climate is changing for metered-dose inhalers and action is needed. Drug Des Devel Ther. 2020;14:3043–3055.
  • Gnopeck M, Gary J, Herena DL, et al. Medicament delivery Formulations, devices and methods WO/2006/101882. 2006
  • Koura. Zephex ® 152a Overview. https://www.zephex.com/wp-content/uploads/2023/04/Zephex-152a-Overview-V3.pdf
  • Commission CPS. Hazardous substances and articles: administration and enforcement regulations. Code Fed Regul. 2011;2:1500–1503.
  • Close J HR, Makar M, Boldt E, et al. HFO-1234ze(E): flammability characterization for metered dose inhaler manufacturing. Respiratory Drug Delivery. 2023; 211–216.
  • Murray J MA, Doidge W. Anti-microbial properties of low-GWP pMDI Propellant P-152a. Respiratory Drug Delivery. 2023; 239–242.
  • Leach C L. The CFC to HFA transition and its impact on pulmonary drug development: discussion. Respir Care. 2005;50(9):1207–1208.
  • Parliament THEE, Council THE, The OF, et al. Regulation (EU) no 517/2014 of the European parliament and of the council of 16 April 2014 on fluorinated greenhouse gases and repealing regulation (EC) no 842/2006. Off J Eur Union. 2014;2014(517):195–230. https://eur-lex.europa.eu/legal-content/EN/TXT/?uri=uriserv:OJ.L_.2014.150.01.0195.01.ENG
  • Amendment to the Montreal Protocol on Substances that Deplete the Ozone Layer. No. 26369. 2016. p. 1–5. https://treaties.un.org/Pages/ViewDetails.aspx?src=IND&mtdsg_no=XXVII-2-b&chapter=27&clang=_en
  • European Chemical Agency. Annex XV restriction report-proposal for a restriction per- and polyfluoroalkyl substances (PFASs). ECHA. 2023. https://echa.europa.eu/documents/10162/f605d4b5-7c17-7414-8823-b49b9fd43aea
  • Öko-Institut. Support contract for an evaluation and impact assessment for amending regulation (EU) no 517/2014 on fluorinated greenhouse gases. CLIMA.A2/ETU/2019/0016/Impact assessment final report - annexes. no. 517. 2022. https://climate.ec.europa.eu/system/files/2022-04/f-gas_evaluation_report_en.pdf
  • Stein SW, Myatt BJ, Cocks P, et al. Experimental and theoretical investigations of pMDI Atomization and plume characteristics using alternative propellants. Respiratory Drug Delivery. 2021;1:15–26.
  • Stein SW, Myrdal PB. The relative influence of atomization and evaporation on metered dose inhaler drug delivery efficiency. Aerosol Sci Technol. 2006;40(5):335–347. doi: 10.1080/02786820600612268
  • Mason-Smith N, Duke DJ, Kastengren AL, et al. Revealing pMDI Spray initial conditions: flashing, atomisation and the effect of ethanol. Pharm Res. 2017;34(4):718–729. doi: 10.1007/s11095-017-2098-2
  • Dunbar C. An experimental and theoretical investigation of the spray issued from a pressurised metered-dose inhaler [Ph.D. Thesis]. Manchester (UK): University of Manchester; 1996.
  • Clark AR. Metered atomisation for respiratory drug delivery [Ph.D. Thesis]. Loughborough (UK): Loughborough University; 1991.
  • Gavtash B, Cooper A, Dexter S, et al. Development of a theoretical model to predict pMDI spray force, using alternative propellant systems. Drug Delivery To The Lungs. 2018;29:76–79.
  • Leach CL, Davidson PJ, Hasselquist BE, et al. Lung deposition of hydrofluoroalkane-134a beclomethasone is greater than that of chlorofluorocarbon fluticasone and chlorofluorocarbon beclomethasone: a cross-over study in healthy volunteers. Chest. 2002 Aug;122(2):510–516. doi: 10.1378/chest.122.2.510
  • Stein SW, Myrdal PB. A theoretical and experimental analysis of formulation and device parameters affecting solution MDI size distributions. J Pharm Sci. 2004;93(8):2158–2175. doi: 10.1002/jps.20116
  • Vutlapalli S,Rao, Lingzhe ,Myatt, Ben et al. Saturated vapor pressure of HFA152a-ethanol and HFO1234ze(E)-ethanol binary mixtures. Drug Delivery To The Lungs. 2022;33:171–174.
  • Gavtash B, Myatt B, O’shea H, Mason F, Lewis D, et al. Saturated vapour pressure (SVP) measurement of ethanol/HFA binary mixtures. J Aerosol Med Pulm Drug Deliv. 2015;29(3):A12–A12. doi: 10.1089/jamp.2016.ab01.abstracts
  • Gavtash B, Versteeg HK, Stein SW. A validated theoretical approach to predict the effect of ambient temperature and ethanol concentration on the event-averaged pMDI droplet size. Drug Delivery To The Lungs. 2019;30:68–71.
  • Shur J, Rossi I, Ganley W, et al. The formulators guide to transitioning to low global warming potential pMdis. Respiratory Drug Delivery. 2022;1:65–74.
  • Rao L,Kusangaya AJ, Marasini N, et al. In-vitro evaluation of pMDI Spray development of HFA134a, HFA152a and HFO1234ze(E). Drug Delivery To The Lungs. 2022;33:179–182.
  • Duke D, Myatt B, Rao L, et al. Optimizing spray formation in solution and suspension low GWP metered dose inhalers. Respiratory Drug Delivery. 2023;1:81–92.
  • Smyth HDC. The influence of formulation variables on the performance of alternative propellant-driven metered dose inhalers. Adv Drug Deliv Rev. 2003;55(7):807–828. doi: 10.1016/S0169-409X(03)00079-6
  • Chierici V, Cavalieri L, Piraino A, et al. Consequences of not-shaking and shake-fire delays on the emitted dose of some commercial solution and suspension pressurized metered dose inhalers commercial solution and suspension pressurized metered dose inhalers. Expert Opin Drug Deliv. 2020;17(7):1025–1039. doi: 10.1080/17425247.2020.1767066
  • D’Angelo D, Chierici V, Quarta E, et al. No-shaking and shake-fire delays affect respirable dose for suspension but not solution pMdis. Int J Pharm. 2022;631(December):122478. 2023. doi: 10.1016/j.ijpharm.2022.122478
  • Corr S, Noakes T. Pressurised metered dose inhaler propellants: going forward. Respiratory Drug Delivery. 2017;2:255–258.
  • Williams RO, Rogers TL, Liu J. Study of solubility of steroids in hydrofluoroalkane propellants. Drug Dev Ind Pharm. 1999;25(12):1227–1234. doi: 10.1081/DDC-100102292
  • Buttini F, Miozzi M, Balducci AG, et al. Differences in physical chemistry and dissolution rate of solid particle aerosols from solution pressurised inhalers. Int J Pharm. 2014 Apr;465(1–2):42–51. doi: 10.1016/j.ijpharm.2014.01.033
  • Marasini N, Koala V, Rao L, et al. Solution-based pressurized metered dose inhaler formulations using HFA134a, HFA152a and HFO1234ze(E) propellants: analysis of size, aerosolization performance and particle morphology. Drug Delivery To The Lungs. 2022;33:167–170.
  • Lewis DA, Green JL, Turner R, et al. HFA152a MDI design: matching the in-vitro performance of HFA227ea and HFA134a MDIs. Respiratory Drug Delivery. 2023;1:295–298.
  • Lewis DA, Young PM, Buttini F, et al. Towards the bioequivalence of pressurised metered dose inhalers 1: design and characterisation of aerodynamically equivalent beclomethasone dipropionate inhalers with and without glycerol as a non-volatile excipient. Eur J Pharm Biopharm. 2014 Jan;86(1):31–37. doi: 10.1016/j.ejpb.2013.02.014
  • Brambilla G GR, Ganderton D, Lewis DA, et al. The modulation of clouds generated by pMdis. J Aerosol Med Pulm Drug Deliv. 1999;12:119.
  • Lewis DA, Green JL, Turner R, et al. Towards pharmaceutical equivalence: a comparison of three MDIs: HFA152a HFA134a and HFA227ea. Respiratory Drug Delivery. 2023;1:299–304.
  • Buttini F, Glieca S, Carretta G, et al. A roadmap for constructing a beclomethasone pMDI Solution using HFA152a. Respiratory Drug Delivery. 2023;1:421–426.
  • Sule A, Sule S, Mullington T, et al. Comparison of in-vitro performance characteristics of salbutamol pMDI with low GWP propellant (HFA-152a) vs the Current propellant (HFA-134a). Drug Delivery To The Lungs. 2022;33:204–207.
  • Kay R, Obirek A, Wegrzyn W, et al. Accelerated stability studies with pMDIs of Respitab HFA-152a propellant dispersible salbutamol tablets. Drug Delivery To The Lungs. 2022;33:212–215.
  • Corr S, Noakes TJ. Pharmaceutical Compositions. WO 2012/156711 Al. 2012.
  • Corr S, Noakes TJ. Pharmaceutical composition. WO 2018/051131. 2018
  • CORR S, Noakes TJ. Pharmaceutical Composition.WO 2018/051128. 2018.
  • Corr S, Noakes TJ. Pharmaceutical composition. WO 2018/051132. 2018
  • Zambelli E, Bonelli S, Copelli D, et al. Stainless Steel Can For Pressurized Metered Dose Inhalers. WO 2021/110239A1. 2021.
  • Zambelli E. Pressurized metered dose inhalers comprising a buffered pharmaceutical formulation. WO 2021/151857. 2021
  • Zambelli E. Pressurized metered dose inhalers comprising a buffered pharmaceutical formulation. WO 2021/165348. 2021
  • Zambelli E, Bonelli S, Copelli D, et al. A pharmaceutical formulation for pressurized metered dose inhaler. WO 2022/074183. 2022
  • Joshi V,Archbell, James, Lachacz, Kellisa et al. Compositions, methods and systems for aerosol Drug Delivery. WO 2023/283438 A. 2023
  • Joshi V,Archbell, James, Lachacz, Kellisa et al. Compositions, methods and systems for aerosol Drug Delivery. WO 2023/283441 A1. 2023
  • Vehring R, Hartman S, Smith ME, et al. Compositions for Respiratory delivery of active agents and associated methods and systems. WO 2010/138862 A2. 2010
  • Decaire B, Conviser S, Sarrailh S, et al. Materials compatibility testing of Honeywell’s new low global warming potential propellants. https://Sustainability.Honeywell.com/Content/Dam/s.
  • Le Corre B, Sarrailh S, Ferrao J. Investigation of leachables from pMdis containing propellants HFA 134a, HFA 152a and HFO 1234ze. Respiratory Drug Delivery. 2022;1:209–212.