{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T15:26:02Z","timestamp":1787153162570,"version":"build-2736575974"},"reference-count":19,"publisher":"SAGE Publications","issue":"6","license":[{"start":{"date-parts":[[2025,8,25]],"date-time":"2025-08-25T00:00:00Z","timestamp":1756080000000},"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":[[2025,12,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>The \u201cMiller\u201d design of mixing inlet (MI) enables a cascade impactor to operate at a constant flow rate while the orally inhaled product-on-test is evaluated at varying flow rates by controlling the flow of air via its side-arm.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Study Purpose:<\/jats:title>\n                    <jats:p>As part of the European Pharmaceutical Aerosol Group (EPAG) Impactor subgroup, we report a cross-industry experimental investigation by five organizations to determine internal losses of different inhaler-generated aerosolized medications within commercially available MIs, focusing on pharmacopeial methods for product testing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>Evaluations were undertaken of solution and suspension formulations delivered by pressurized metered dose inhalers (pMDIs), passive dry powder inhalers (DPIs), and compressed air-jet and vibrating mesh nebulizers. Four different apparatuses were evaluated at different constant air flow rates entering the MI side arm. The nebulizers were tested utilizing a variable adult flow profile generated by a breathing simulator.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>Losses within the MI were generally &lt;5%, expressed as a percentage of the delivered mass of active pharmaceutical ingredient (API) ex-inhaler. These losses were sufficiently small that they can in most cases be accommodated within the allowance of \u00b15% OIP label claim emitted mass\/actuation in the pharmacopeial compendia for total internal losses for aerodynamic particle size distribution (APSD) determination. However, corresponding average losses were between 2.8% and 5.2% of the mass of API presented to the MI for the blister-based DPIs. APSD-derived measures were largely unaffected by the magnitude of pressurized air flow up to 60 L\/min to the side-arm of the MI, except for the solution-formulated pMDI, where increasing flow rate was associated with reduced mass median aerodynamic diameter and increased geometric standard deviation, suggestive of a dependency related to ethanol co-solvent evaporation rate.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>MI loss evaluation should be considered an important part of method development to minimize internal losses of the aerosolized medication being sampled.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/19412711251370473","type":"journal-article","created":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T16:59:29Z","timestamp":1765299569000},"page":"373-385","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Multi-Participant Blinded Investigation into Internal Losses of Medication in Commercially Available Mixing Inlets: Testing Different Orally Inhaled Product Classes Following Pharmacopeial Methods"],"prefix":"10.1177","volume":"38","author":[{"given":"Patrik U.","family":"Andersson","sequence":"first","affiliation":[{"name":"Inhalation Product Development, AstraZeneca R&amp;D Gothenburg, M\u00f6lndal, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jim","family":"Clay","sequence":"additional","affiliation":[{"name":"Kindeva Drug Delivery, Loughborough, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Parry","sequence":"additional","affiliation":[{"name":"Intertek Melbourn, Melbourn, Cambridge, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa","family":"Iley","sequence":"additional","affiliation":[{"name":"Intertek Melbourn, Melbourn, Cambridge, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5667-6083","authenticated-orcid":false,"given":"Daryl L.","family":"Roberts","sequence":"additional","affiliation":[{"name":"Applied Particle Principles LLC, Hamilton, Virginia, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lois","family":"Slator","sequence":"additional","affiliation":[{"name":"University of Hertfordshire, Hatfield, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00e5rten","family":"Svensson","sequence":"additional","affiliation":[{"name":"Emmace Consulting AB, Lund, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hlack","family":"Mohammed","sequence":"additional","affiliation":[{"name":"GSK plc, Ware, Hertfordshire, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5456-8425","authenticated-orcid":false,"given":"Jolyon P.","family":"Mitchell","sequence":"additional","affiliation":[{"name":"Jolyon Mitchell Inhaler Consulting Services Inc., London, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,8,25]]},"reference":[{"key":"e_1_3_3_2_2","volume-title":"European Pharmacopoeia 11, Monograph 2.9.18. Preparations for inhalation: Aerodynamic assessment of fine particles","author":"European Directorate for Quality in Medicines and Healthcare (EDQM)","year":"2024","unstructured":"European Directorate for Quality in Medicines and Healthcare (EDQM). European Pharmacopoeia 11, Monograph 2.9.18. Preparations for inhalation: Aerodynamic assessment of fine particles. EDQM, Strasbourg, France; 2024."},{"key":"e_1_3_3_3_2","volume-title":"Chapter <601> Inhalation and drug products: Aerosols, Sprays and Powders\u2014Performance Quality Tests.","author":"United States Pharmacopeial Convention","year":"2024","unstructured":"United States Pharmacopeial Convention. Chapter <601> Inhalation and drug products: Aerosols, Sprays and Powders\u2014Performance Quality Tests. USP\/NF: Rockville, MD, USA; 2024."},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1021\/es60092a003"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1089\/089426803772455622"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1089\/089426803769017668"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1089\/jamp.2012.0986"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1208\/s12249-017-0860-8"},{"key":"e_1_3_3_9_2","article-title":"Apparatus and process for aerosol size measurement at varying gas flow rates","volume":"6","author":"Miller NC","year":"2002","unstructured":"Miller NC. Apparatus and process for aerosol size measurement at varying gas flow rates. US Patent, 2002; 6435,004-B1.","journal-title":"US Patent"},{"key":"e_1_3_3_10_2","first-page":"191","volume-title":"Aerodynamic Sizing with Simulated Inhalation Profiles: Total Dose Capture and Measurement","author":"Miller NC","year":"2000","unstructured":"Miller NC, , Maniaci MJ, , Dwivedi S, et al. Aerodynamic Sizing with Simulated Inhalation Profiles: Total Dose Capture and Measurement. Respiratory Drug Delivery-VII Serentec Press; 2000, 191\u2013196."},{"key":"e_1_3_3_11_2","unstructured":"Clayton J. Copley Scientific Ltd. private communication. 2024."},{"key":"e_1_3_3_12_2","volume-title":"Chapter <1601> Products for nebulization","author":"United States Pharmacopeial Convention","year":"2024","unstructured":"United States Pharmacopeial Convention. Chapter <1601> Products for nebulization. USP\/NF: Rockville, MD, USA; 2024."},{"key":"e_1_3_3_13_2","volume-title":"European Pharmacopoeia 11, Monograph 2.9.44.","author":"European Directorate for Quality in Medicines and Healthcare (EDQM)","year":"2024","unstructured":"European Directorate for Quality in Medicines and Healthcare (EDQM). Preparations for nebulisation. In European Pharmacopoeia 11, Monograph 2.9.44. EDQM: Strasbourg, France; 2024."},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.4187\/respcare.07520984"},{"key":"e_1_3_3_15_2","volume-title":"EMA\/CHMP\/20607\/2024","author":"European Medicines Agency (EMA)","year":"2024","unstructured":"European Medicines Agency (EMA). Draft guideline on the pharmaceutical quality of inhalation and nasal medicinal products. EMA\/CHMP\/20607\/2024. 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