{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:58:45Z","timestamp":1785437925248,"version":"3.56.0"},"reference-count":52,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T00:00:00Z","timestamp":1777939200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fund for Scientific Research","award":["24907174"],"award-info":[{"award-number":["24907174"]}]},{"award":["24907174"],"award-info":[{"award-number":["24907174"]}],"id":[{"id":"https:\/\/ror.org\/03q83t159","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Laboratoires SMB"},{"id":[{"id":"https:\/\/ror.org\/03jbf2g44","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background\/Objectives: The development of dry powder formulations for pulmonary delivery of therapeutic antibodies requires careful stabilization strategies to preserve protein integrity during spray-drying and long-term storage. This study investigates the impact of various sugar-derivatives, a polyol (D-mannitol), a disaccharide (D-sucrose) and a polysaccharide (dextran 10 kDa), used individually or in combination, on the physical stability of bovine polyclonal immunoglobulin G (pAb) in dry powders for inhalation (DPIs). Methods: A design of experiments (DoE) approach was employed to evaluate the effects of these excipients on residual moisture (RM), low-order aggregates (LOA) and high-order aggregates (HOA), immediately after spray-drying (T0) and after 10 months of storage at room temperature in a desiccator (T10). Results: All DPIs exhibited a high amorphous content and a favorable glass transition temperature, with RM decreasing over time. The combination of D-mannitol and dextran 10 kDA (DPI-MD) demonstrated the most effective stabilization, minimizing LOA and HOA formation at T0 and T10. Although the ternary mixture, including D-sucrose (DPI-MSD) exhibited higher process stability, it was less stable over time in comparison to the binary mixture. The aerodynamic performance of these carrier-free DPIs, assessed via laser diffraction (% \u02c2 5 \u00b5m), were between 51 \u00b1 3 (DPI-MD) and 67 \u00b1 4 (DPI MSD) and a Next Generation Impactor, confirmed that formulation produced aerosol with suitable size distribution and fine particle fractions (FPFn upt to 71 \u00b1 5% for DPI-MSD), for deep pulmonary deposition. Conclusions: These findings highlight the importance of combining excipients with complementary physical properties to achieve robust protein stabilization. The DPI-MD emerged as the most promising candidate for pAb lung delivery, balancing protein integrity, powder stability, and aerodynamic efficiency.<\/jats:p>","DOI":"10.3390\/pharmaceutics18050573","type":"journal-article","created":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T10:01:30Z","timestamp":1777975290000},"page":"573","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Optimization of Sugar-Derivatives Mixtures for Stabilizing Polyclonal Immunoglobulin G in Spray-Dried Inhalable Powders During Processing and Long-Term Storage"],"prefix":"10.3390","volume":"18","author":[{"given":"Philippe","family":"Gevenois","sequence":"first","affiliation":[{"name":"Unit of Pharmaceutics and Biopharmaceutics, Universit\u00e9 Libre de Bruxelles (ULB), 1050 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-0507-2614","authenticated-orcid":false,"given":"Le Van","family":"Bui","sequence":"additional","affiliation":[{"name":"Unit of Pharmaceutics and Biopharmaceutics, Universit\u00e9 Libre de Bruxelles (ULB), 1050 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thami","family":"Sebti","sequence":"additional","affiliation":[{"name":"Research and Development Department, Laboratoires S.M.B., 1080 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7788-9886","authenticated-orcid":false,"given":"Yvan Vander","family":"Heyden","sequence":"additional","affiliation":[{"name":"Department of Analytical Chemistry, Applied Chemometrics and Molecular Modelling, Vrije Universiteit Brussel (VUB), 1090 Jette, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karim","family":"Amighi","sequence":"additional","affiliation":[{"name":"Unit of Pharmaceutics and Biopharmaceutics, Universit\u00e9 Libre de Bruxelles (ULB), 1050 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2445-5790","authenticated-orcid":false,"given":"Nathalie","family":"Wauthoz","sequence":"additional","affiliation":[{"name":"Unit of Pharmaceutics and Biopharmaceutics, Universit\u00e9 Libre de Bruxelles (ULB), 1050 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1038\/256495a0","article-title":"Continuous cultures of fused cells secreting antibody of predefined specificity","volume":"256","author":"Kohler","year":"1975","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1038\/381751a0","article-title":"Clonal selection and learning in the antibody system","volume":"381","author":"Rajewsky","year":"1996","journal-title":"Nature"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/j.crvi.2006.02.006","article-title":"Monoclonal antibodies: Technology around the clock for new therapeutic hopes","volume":"329","author":"Bourel","year":"2006","journal-title":"Comptes Rendus Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/S0001-2998(89)80014-5","article-title":"Practical considerations in the production, purification, and formulation of monoclonal antibodies for immunoscintigraphy and immunotherapy","volume":"19","author":"Bogard","year":"1989","journal-title":"Semin. 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