Potential use of cellulose nanocrystals as multifunctional excipient in chlorphenamine maleate nasal spray formulations

Nasal spray performance depends strongly on excipient properties, which govern plume formation, droplet size, and mucociliary retention. However, currently available excipients rarely combine these functionalities. In alignment with the FDA’s PRIME initiative for excipient modernisation, we demonstrate that cellulose nanocrystals (CNCs) represent a promising class of multifunctional excipients. As a case study, we evaluated CNCs as multifunctional excipients in chlorphenamine maleate (CM) formulations. Samples containing up to 2 wt% CNC delivered uniform doses, tunable plume areas (30–61 cm2), and stable droplet sizes (d50 = 116–189 µm). Owing to their anisotropic shape, the nanoparticles exhibited shear-thinning behaviour with partial viscosity recovery after shear. However, the presence of CM significantly amplified thixotropy and increased suspension viscosity up to 200-fold at higher CNC concentrations (i.e. 4 wt%). Calorimetric measurements revealed the spontaneous character of the CM–CNC interactions (ΔG = −26.7 kJ/mol), with exothermic enthalpy (ΔH = −15.5 kJ/mol) and a positive entropic term (ΔS = 37.38 J/(mol·K)), suggesting a significant hydrophobic contribution to binding affinity. Such interactions increased CM solubility three-fold (25–80 mg mL−1), enabling substantially higher drug loading. At CNC concentrations above 2 wt%, gelation occurred and prevented spray formation. Overall, these results demonstrate that CNCs can function as multifunctional excipients for nasal spray formulations by simultaneously tuning spray performance and enhancing drug solubility.