{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T11:06:12Z","timestamp":1775819172011,"version":"3.50.1"},"reference-count":31,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2021,12,30]],"date-time":"2021-12-30T00:00:00Z","timestamp":1640822400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Scientific Research Deanship, University of Ha\u2019il, Saudi Arabia","award":["RG-20 131"],"award-info":[{"award-number":["RG-20 131"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Terbinafine is a broad-spectrum antifungal agent with therapeutic potential against pulmonary aspergillosis. The main aim of the current study was to investigate the potential of l-leucine, alone and in combination with mannitol, to improve the performance of spray-dried terbinafine microparticles for inhalation. The study also aimed to investigate the potential of the low resistance Cyclohaler\u00ae and the high resistance Handihaler\u00ae as inhalation devices for spray-dried microparticles. To this end, eight powder inhalation formulations of terbinafine were prepared by nano spray drying via a factorial experimental design. The formulations were evaluated in vitro for their potential to deliver the antifungal drug to the lungs using the Cyclohaler\u00ae and the Handihaler\u00ae. Leucine was superior as an excipient to mannitol and to mixtures of leucine and mannitol. Using leucine as an excipient resulted in formulations with fine particle fractions of up to 60.84 \u00b1 0.67% w\/w and particle mass median aerodynamic diameters of down to 1.90 \u00b1 0.20 \u03bcm, whereas using mannitol as an excipient resulted in formulations with fine particle fractions of up to 18.75 \u00b1 3.46% w\/w and particle mass median aerodynamic diameters of down to 6.79 \u00b1 0.82 \u03bcm. When leucine was used as an excipient, using 50% w\/w rather than 25% w\/w ethanol in water as a spray solvent enhanced the dispersibility of the particles, with a mean absolute increase in the formulation fine particle fraction of 9.57% w\/w (95% confidence interval = 6.40\u201312.73% w\/w). This was potentially underlain by enrichment of the particle surfaces with leucine. The Cyclohaler\u00ae outperformed the Handihaler\u00ae as an inhalation device for the developed formulations, with a mean absolute increase in the fine particle fraction of 9.17% w\/w (95% confidence interval = 8.17\u201310.16% w\/w).<\/jats:p>","DOI":"10.3390\/pharmaceutics14010087","type":"journal-article","created":{"date-parts":[[2021,12,30]],"date-time":"2021-12-30T23:29:07Z","timestamp":1640906947000},"page":"87","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Inhalable, Spray-Dried Terbinafine Microparticles for Management of Pulmonary Fungal Infections: Optimization of the Excipient Composition and Selection of an Inhalation Device"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1913-9005","authenticated-orcid":false,"given":"Khaled","family":"Almansour","sequence":"first","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy, University of Ha\u2019il, Hail 55473, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1313-1283","authenticated-orcid":false,"given":"Iman M.","family":"Alfagih","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 12372, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5947-986X","authenticated-orcid":false,"given":"Alhassan H.","family":"Aodah","sequence":"additional","affiliation":[{"name":"National Center of Biotechnology, Life Science & Environment Research Institute, King Abdulaziz City for Science and Technology (KACST), Riyadh 11442, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8997-0788","authenticated-orcid":false,"given":"Fawaz","family":"Alheibshy","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy, University of Ha\u2019il, Hail 55473, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9892-2158","authenticated-orcid":false,"given":"Raisuddin","family":"Ali","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 12372, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6595-3097","authenticated-orcid":false,"given":"Turki","family":"Al Hagbani","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy, University of Ha\u2019il, Hail 55473, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5779-8170","authenticated-orcid":false,"given":"Mustafa M.A.","family":"Elsayed","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy, University of Ha\u2019il, Hail 55473, Saudi Arabia"},{"name":"Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Alexandria 21521, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1183\/09059180.00001011","article-title":"Pulmonary aspergillosis: A clinical review","volume":"20","author":"Kousha","year":"2011","journal-title":"Eur. 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