<span class="word">Optimization <span class="word">of <span class="word"><span class="changedDisabled">Sugar-<span class="word"><span class="changedDisabled">Derivatives <span class="word"><span class="changedDisabled">Mixtures <span class="word">for <span class="word"><span class="changedDisabled">Stabilizing <span class="word"><span class="changedDisabled">Polyclonal <span class="word"><span class="changedDisabled">Immunoglobulin <span class="word">G <span class="word">in <span class="word"><span class="changedDisabled">Spray-<span class="word"><span class="changedDisabled">Dried <span class="word"><span class="changedDisabled">Inhalable <span class="word"><span class="changedDisabled">Powders <span class="word"><span class="changedDisabled">During <span class="word"><span class="changedDisabled">Processing <span class="word">and <span class="word"><span class="changedDisabled">Long-<span class="word"><span class="changedDisabled">Term <span class="word"><span class="changedDisabled"

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 10kDa) 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 aggre-gates (LOA) and high-order aggregates (HOA), immediately after spray-drying (T0) and after 10 months of storage at room temperature (T10) in a desiccator. Results: All DPIs exhibited a high amorphous content and a favorable glass transition temperature, with RM decreasing over time. A combination of D-mannitol and dextran 10kDA (DPI-MD) demonstrated the best stabilization, minimizing LOA and HOA formation, both at T0 and T10. A ternary mixture, including also D-sucrose (DPI-MSD), showed enhanced short-term stability, but was less stable over time. The aerodynamic perfor-mance of these carrier-free DPIs, assessed via laser diffraction and a Next Generation Impactor, confirmed that DPI-MD and DPI-MSD formulations produced aerosol with suitable size distribution and fine particle fractions (FPFn of 70 ± 5% for DPI-MSD), for deep pulmonary deposition. Conclusions: These findings highlight the importance of combining excipients with complementary physical properties to achieve robust pro-tein stabilization. The DPI-MD emerged as the most promising candidate for pAb lung delivery, balancing protein integrity, powder stability, and aerodynamic efficiency.