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Changes in chemicophysical properties will alter product performance, impacting <jats:italic>in-vitro<\/jats:italic> bioequivalence metrics. This study investigates those differences using equivalent pMDI hardware and formulations.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>Aerodynamic particle size distribution (APSD) measurements, laser diffraction and high-speed imaging were used to compare the performance of HFA134a, HFA152a and HFO1234ze(E) solution formulations of beclomethasone dipropionate. Propellant-only placebos, cosolvent-free solutions, and ethanol solutions at 8% and 15% w\/w were investigated.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>HFA152a formulations had increased drug deposition on the actuator and throat while HFO1234ze(E) produced comparable APSD performance to HFA134a formulations. Plumes from HFA152a formulations spread more rapidly and were less stable and repeatable than those from HFA134a. HFO1234ze(E) plumes spread more slowly than HFA134a, but converged with HFA134a ex-mouthpiece. Differences between propellants were moderated by the addition of ethanol.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>Plume stability is a driver of differences between formulations in the near-orifice region. Shot-to-shot repeatability differences are more pronounced ex-mouthpiece, where mixing with ambient air is dominant. Modifications to low-GWP pMDI product actuator orifice and mouthpiece geometries may provide a route to improved <jats:italic>in-vitro<\/jats:italic> product bioequivalence relative to current pMDIs. Differences between formulations are modest and may be managed through a combination of formulation, orifice and mouthpiece geometry changes. These generic formulations provide a database of benchmark data against which the performance of low-GWP products may be compared.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1007\/s11095-025-03830-6","type":"journal-article","created":{"date-parts":[[2025,2,12]],"date-time":"2025-02-12T21:38:38Z","timestamp":1739396318000},"page":"385-400","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["In-vitro Evaluation of Solution Pressurised Metered Dose Inhaler Sprays with Low-GWP Propellants"],"prefix":"10.1007","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8692-6493","authenticated-orcid":false,"given":"Daniel J.","family":"Duke","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingzhe","family":"Rao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Myatt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phil","family":"Cocks","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Stein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nirmal","family":"Marasini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui Xin","family":"Ong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Young","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,2,12]]},"reference":[{"issue":"1\u20132","key":"3830_CR1","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1016\/s0022-1139(02)00191-4","volume":"118","author":"T Noakes","year":"2002","unstructured":"Noakes T. 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