Polymer-Gated Bilayer Buccoadhesive Tablets for Biphasic Release of Indomethacin: Balancing Dissolution and Mucoadhesion

Objectives: To address the critical limitations of current formulations that fail to simultaneously resolve indomethacin’s poor water solubility, susceptibility to gastric acid hydrolysis, and difficulty in balancing rapid onset with long-term sustained release, this study prepared solid dispersions via anti-solvent freeze-drying to improve drug dissolution, constructed oral buccoadhesive bilayer controlled-release tablets using direct powder compression, and elucidated the intrinsic relationships among polymer gel properties, swelling-erosion behavior, tablet integrity maintenance, and drug release mechanisms. Methods: Solid dispersions (SDs) were prepared by anti-solvent freeze-drying. Bilayer tablets (25 mg IND/tablet, 12.5 mg/layer) were fabricated via direct powder compression after optimizing disintegrants and polymer matrices. In vitro dissolution, surface pH, adhesion time, and adhesion strength were evaluated. Results: SDs enhanced dissolution by at least 30-fold in water and 2.4-fold at pH 6.8 within 2 h versus pure drug. Optimized bilayer tablets achieved 45% drug release at 20 min and 80% sustained release over 8 h, with surface pH of 6.8 ± 0.1, adhesion time of 8.3 ± 0.1 h, and adhesion strength of 57 ± 0.13 g. Conclusions: The physicochemical properties of polymeric excipients are critical for balancing drug release and mucoadhesion in buccal tablets. To achieve ideal controlled-release effects, in addition to focusing on the swelling and erosion characteristics of matrix-based tablets, the ability to maintain tablet integrity during dynamic dissolution must be further investigated, which is an essential factor for ensuring precisely modulated drug release. Meanwhile, when employing solid dispersions as solubilizing intermediates to prepare controlled-release formulations, the gelling properties of polymers in each formulation component should be fully considered to avoid incomplete disintegration and insufficient release at the initial dissolution stage.