{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T03:07:22Z","timestamp":1784257642287,"version":"3.55.0"},"reference-count":18,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2025,2,1]],"date-time":"2025-02-01T00:00:00Z","timestamp":1738368000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Aerosol Medicine and Pulmonary Drug Delivery"],"published-print":{"date-parts":[[2025,2,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>A fixed combination of formoterol, glycopyrrolate, and beclomethasone dipropionate is approved in some geographic areas as pressurized metered dose inhaler (pMDI) formulation for the treatment of asthma and chronic obstructive pulmonary disease. Current pMDIs use hydrofluoroalkanes (HFAs) as a propellant, such as 1,1,1,2-tetrafluoroethane (HFA134a), that have a high global warming potential (GWP), but their use is being progressively lowered to reduce impact on climate. One option to reduce the carbon footprint of the pMDI products while preserving pMDIs as a therapeutic option is reformulating the current pMDIs using low GWP propellants, such as 1,1-difluoroethane (HFA152a). Nevertheless, pharmaceutical, clinical, and regulatory challenges need to be considered when reformulating a pMDI. A nonclinical study in rodents has been performed to support the formulation work and optimize the design of the bioequivalence study in humans.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>A fixed combination of formoterol, glycopyrrolate, and beclomethasone dipropionate (BDP) as pMDI with the two propellants HFA134a or HFA152a was administered by inhalation to Sprague\u2013Dawley rats, using inhalation tower, to assess the impact of the propellant on the PK profile of the active components. After administration, serial blood samples were taken from each rat, and plasma aliquots were analyzed by HPLC-MS\/MS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Inhalation administration to rats of the fixed triple combination as pMDI showed similar PK profile for formoterol, glycopyrrolate, and BDP with the two propellants. Exposure parameters C\n                      <jats:sub>max<\/jats:sub>\n                      and AUC\n                      <jats:sub>last<\/jats:sub>\n                      of the three active ingredients were compared, showing no statistically significant differences in the systemic exposure between the two treatment groups. Higher interanimal variability was observed for the metabolite beclomethasone 17-monopropionate, likely due to individual differences in the metabolite generation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Considering these data, it was possible to conclude that replacing propellant HFA134a with HFA152a in a newly developed formulation had no significant impact on the plasmatic PK profile of formoterol, glycopyrrolate, and BDP in rats after inhalation administration using inhalation towers.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1089\/jamp.2024.0019","type":"journal-article","created":{"date-parts":[[2024,9,26]],"date-time":"2024-09-26T04:46:37Z","timestamp":1727325997000},"page":"18-25","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Comparison of Formoterol, Glycopyrrolate, and Beclomethasone Dipropionate Pharmacokinetic Profile after Inhaled Administration as pMDI Using HFA134a or HFA152a Propellant: Preclinical Assessment of Drug Exposure in Sprague\u2013Dawley Rat Model"],"prefix":"10.1177","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-0922-7134","authenticated-orcid":false,"given":"Alessandro","family":"Fioni","sequence":"first","affiliation":[{"name":"Department of Pharmacokinetics, Biochemistry and Metabolism, Chiesi Farmaceutici S.p.A, Parma, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giandomenico","family":"Brogin","sequence":"additional","affiliation":[{"name":"Department of Pharmacokinetics, Biochemistry and Metabolism, Chiesi Farmaceutici S.p.A, Parma, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Puccini","sequence":"additional","affiliation":[{"name":"Department of Pharmacokinetics, Biochemistry and Metabolism, Chiesi Farmaceutici S.p.A, Parma, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew Dennis","family":"Allen","sequence":"additional","affiliation":[{"name":"Department of Experimental Pharmacology and Translational Science, Chiesi Farmaceutici S.p.A, Parma, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Miglietta","sequence":"additional","affiliation":[{"name":"Department of Experimental Pharmacology and Translational Science, Chiesi Farmaceutici S.p.A, Parma, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erika","family":"Cuoghi","sequence":"additional","affiliation":[{"name":"Global Technical Development, Chiesi Farmaceutici S.p.A., Parma, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrico","family":"Zambelli","sequence":"additional","affiliation":[{"name":"Global Technical Development, Chiesi Farmaceutici S.p.A., Parma, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Loredana","family":"Battipaglia","sequence":"additional","affiliation":[{"name":"Department of Safety and Toxicology, Chiesi Farmaceutici S.p.A., Parma, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,2,3]]},"reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12931-023-02549-5"},{"key":"e_1_3_5_3_2","first-page":"rgae090","article-title":"Advances in inhaler therapy for asthma and chronic obstructive pulmonary disease: A comprehensive review of Fostair\u2122 and Trimbow\u2122","author":"Foster K","year":"2024","unstructured":"Foster K, , Wong CYJ. Advances in inhaler therapy for asthma and chronic obstructive pulmonary disease: A comprehensive review of Fostair\u2122 and Trimbow\u2122. J Pharm Pharmacol, 2024; rgae090; doi: 10.1093\/jpp\/rgae090","journal-title":"J Pharm Pharmacol"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmjresp-2020-000571"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jclepro.2019.117733"},{"key":"e_1_3_5_6_2","unstructured":"European Medicines Agency. Draft Guideline on the Requirements for Demonstrating Therapeutic Equivalence between Orally Inhaled Products (OIP) for Asthma and Chronic Obstructive Pulmonary Disease (COPD). Reference number: EMA\/CHMP\/101453\/2024. Amsterdam NL; 2024. Available from: https:\/\/www.ema.europa.eu\/en\/requirements-demonstrating-therapeutic-equivalence-between-orally-inhaled-products-oip-asthma-chronic-obstructive-pulmonary-disease-copd"},{"key":"e_1_3_5_7_2","unstructured":"European Medicines Agency. Guideline on the Investigation of Bioequivalence. Reference number: CPMP\/EWP\/QWP\/1401\/98 Rev. 1. Amsterdam NL; 2010. Available from: https:\/\/www.ema.europa.eu\/en\/investigation-bioequivalence-scientific-guideline"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-199426010-00001"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/0954-6111(95)90085-3"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25052903"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2020.06.029"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.4155\/tde-2000-0000"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pupt.2024.102299"},{"key":"e_1_3_5_14_2","unstructured":"NC3Rs. What are the 3Rs? London UK; 2024. 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