{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T17:13:02Z","timestamp":1783617182730,"version":"3.55.0"},"reference-count":36,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T00:00:00Z","timestamp":1783555200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Recovery and Resilience Plan","award":["1409"],"award-info":[{"award-number":["1409"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background\/Objectives: Dry powder inhalation (DPI) is a promising strategy for the treatment of respiratory diseases such as cystic fibrosis (CF), where thick and viscous mucus limits drug penetration and contributes to persistent infection and inflammation. Although inhalation allows rapid drug action with reduced systemic exposure, its efficacy depends on the ability of inhaled drugs to achieve and maintain therapeutic concentrations in the lungs and to overcome airway barriers. This study aimed to develop and characterize effervescent dry powder formulations designed to enhance mucus permeabilization through mechanical disruption while delivering an antibiotic. Methods: Effervescent microparticles containing sodium bicarbonate, an organic acid (citric or tartaric acid), and levofloxacin were produced by spray drying using a triple-fluid nozzle to control component distribution and prevent premature effervescence. The influence of functional excipients, including L-leucine and mannitol, on particle formation, aerosol performance, and process yield was evaluated. Microparticles were characterized in terms of morphology, fine particle fraction (FPF), and effervescence-related properties. Results: Formulations containing L-leucine and citric acid reduced particle agglomeration and achieved a fine particle fraction of up to approximately 18%, although with a lower process yield. In contrast, formulations based on tartaric acid and mannitol improved both production yield and aerosol performance, with FPF values increasing up to 27.3% and more efficient CO2 release. The resulting microparticles exhibited spherical, hollow, and partially fragmented morphology, consistent with premature CO2 generation during spray drying. Conclusions: The effervescent approach, combined with controlled spray drying parameters, represents a promising formulation strategy to modulate particle behavior and drug release in mucus-relevant environments. These findings support further investigation of effervescent DPI systems for improved pulmonary drug delivery in CF.<\/jats:p>","DOI":"10.3390\/pharmaceutics18070837","type":"journal-article","created":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T16:16:44Z","timestamp":1783613804000},"page":"837","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Design and Production of Respirable Effervescent Microparticles to Enhance Drug Penetration Through Lung Mucus"],"prefix":"10.3390","volume":"18","author":[{"given":"Valentina","family":"Ruggiero","sequence":"first","affiliation":[{"name":"Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132, 84084 Fisciano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Mariano","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132, 84084 Fisciano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Domenico","family":"Larobina","sequence":"additional","affiliation":[{"name":"Institute of Polymers, Composites and Biomaterials, National Research Council of Italy, P.le E. Fermi, 1, 80055 Portici, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0333-6330","authenticated-orcid":false,"given":"Gaetano","family":"D\u2019Avino","sequence":"additional","affiliation":[{"name":"Dipartimento di Ingegneria Chimica, dei Materiali e della Produzione Industriale, Universit\u00e0 degli Studi di Napoli Federico II, P. le Tecchio 80, 80125 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5857-2552","authenticated-orcid":false,"given":"Marco","family":"Trofa","sequence":"additional","affiliation":[{"name":"Dipartimento di Ingegneria Chimica, dei Materiali e della Produzione Industriale, Universit\u00e0 degli Studi di Napoli Federico II, P. le Tecchio 80, 80125 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1237-7350","authenticated-orcid":false,"given":"Giovanni","family":"Falcone","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132, 84084 Fisciano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3852-4523","authenticated-orcid":false,"given":"Pasquale","family":"Del Gaudio","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132, 84084 Fisciano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4362-4388","authenticated-orcid":false,"given":"Paola","family":"Russo","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132, 84084 Fisciano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Party, P., Piszman, Z.I., Farkas, \u00c1., and Ambrus, R. 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