Sustainable hydrogen peroxide oxidation of carboxylated cellulose nanocrystals: efficient modulation of carboxyl content, hydrophilicity, and particle size for tablet formulation and drug release

Abstract

Carboxylated cellulose nanocrystals (CNCs) were successfully prepared via a green and sustainable hydrogen peroxide (H₂O₂) oxidation method. Compared with conventional acid hydrolysis, this approach not only avoids residual sulfate groups but also enables precise control over particle size and surface functionalization. The H₂O₂-derived CNCs exhibited higher specific surface area (6.32 m² g⁻¹), tunable particle size, and carboxyl groups. Systematic evaluation demonstrated significant improvements in tablet compactibility and drug release under direct compression. In particular, CNCs oxidized for 9 h (CNCs-9 h) showed outstanding performance, achieving high hardness (75.3 N), rapid static disintegration (10 s), and a high release rate (96.8%). Mechanistic analysis revealed that size tunability and enhanced carboxyl density promoted stronger drug binding and dispersion, accelerated water penetration, and facilitated drug diffusion, thereby improving drug loading and release efficiency. Overall, H₂O₂ oxidation provides a sustainable CNCs preparation strategy that enhances excipient performance and offers new insights into efficient tablet formulation and drug delivery.