Cellulose-Based Polymer Blends for Oral Mucoadhesion: Impact of Hydration and Surface Interactions

Hydration, interfacial interactions, and matrix stability are critical determinants of the mucoadhesive behavior of cellulose-based polymers. In this study, we investigated the physicochemical and mucoadhesive behavior of hydroxypropyl methylcellulose (HPMC), Carbopol 974P NF, and Kollidon VA 64, along with their binary blends (1:1, w/w) in the context of oral mucosal drug delivery. Wettability, surface free energy, mucoadhesion, and hydration-induced morphological changes were systematically evaluated using contact angle measurements, adhesion and water uptake studies, and real-time surface dissolution imaging (SDi2). The investigated systems displayed markedly different water contact angles: HPMC 103.4 ± 2.7°, Carbopol 47.2 ± 2.3°, Kollidon 36.0 ± 1.8°, HPMC:Carbopol 51.3 ± 2.8°, and HPMC:Kollidon 53.9 ± 3.4°. The corresponding surface free energy (SFE) values ranged from 12.0 mJ/m² for HPMC to 70.5 mJ/m² for Kollidon. Experiments were performed under saliva-mimicking conditions containing 0.1% (w/v) mucin. The HPMC:Carbopol blend exhibited superior mucoadhesive performance and mechanical stability compared with HPMC alone or with the HPMC:Kollidon blends. In 2% (w/v) mucin, the HPMC:Carbopol blend reached a mucoadhesive force of approximately 1.35 N, whereas HPMC and HPMC:Kollidon showed lower values of approximately 0.5-0.75 N and 0.60 N, respectively. After 96 h at 85% RH, the swelling index increased from 14.8 ± 0.5% for HPMC to 29.4 ± 0.3% for HPMC:Carbopol. The incorporation of Carbopol increased the polar contribution to the surface free energy of HPMC-based blends and promoted stable gel layer formation, whereas Kollidon-containing systems underwent rapid disintegration and asymmetric deformation. SDi2 imaging showed that the HPMC disk changed proportionally by approximately 18% in both height and width during 12 h, whereas the HPMC:Kollidon disk almost completely dissolved after approximately 6 h. These results demonstrate that rational selection and combination of cellulose-based polymers can be used to control hydration, interfacial properties, and mucoadhesion, with HPMC:Carbopol blends showing strong potential for oral mucosal drug delivery.