(T1330-08-54) Mucoadhesive Buccal Tablets: A Patient-Centric Approach to Oral Mucosal Drug Delivery

Purpose: Ongoing innovation in patient-centric drug delivery aims to improve convenience, reduce dosing frequency, and enhance efficacy to increase patient compliance. Mucoadhesion is a promising strategy to achieve these objectives. Oral mucosal drug delivery, in particular, offers benefits such as rapid onset of action and avoidance of first-pass metabolism compared to traditional oral routes [1]. However, the dynamic environment of the oral cavity can limit drug residence time, reduce therapeutic efficacy, and compromise patient compliance [2]. To overcome these challenges, there is growing interest in developing robust mucoadhesive formulations with extended contact time and sustained drug release, ultimately improving both drug efficacy and patient adherence. Our research focused on developing buccal tablets with mucoadhesive polymers to enhance mucosal retention and provide sustained drug delivery. Carbopol® polymers, which are crosslinked polyacrylic acid polymers, serve as highly efficient matrix formers at low inclusion levels and offer excellent mucoadhesive properties [3]. Leveraging the multifunctionality of Carbopol® polymers, we developed robust buccal tablets. Amlexanox, a small-molecule anti-inflammatory and antiallergic agent primarily used in the treatment of canker sores, was selected as a model drug [4][5]. For comparison, similar formulations were prepared using alternative mucoadhesive polymers such as hydroxypropyl methylcellulose, sodium alginate, and chitosan. The resulting buccal tablets were assessed for their physical characteristics, mucoadhesive properties, and drug release profiles.

Methods: Mucoadhesive polymers, including Carbopol® 971P NF polymer, Carbopol® 71G NF polymer, hydroxypropyl methylcellulose (HPMC), sodium alginate and chitosan were selected and formulated into buccal tablets via direct compression (7 mm flat round punch). Two commercial buccal tablet products, Metronidazole Oral Sticking Patches and Dexamethasone Acetate Adhesive Tablets were used as benchmarks. Tablets were evaluated for physical properties: tablet weight (target 75mg); tablet hardness (target > 100 N) and friability (target < 1%). Mucoadhesion performance was assessed using an internally developed method based on the in vitro oesophageal retention (IVOR) model that allows for mucoadhesion evaluation in a dynamic environment (Figure 1) [6]. Drug dissolution was measured using United States Pharmacopeia (USP) Apparatus 2 (50 rpm, 900 mL). Artificial saliva was used as the medium for both IVOR and drug dissolution test. The target for mucoadhesion performance was set as tablet retention time of at least 6 hours, with sustained drug release exceeding 80% within that period.

Results: The physical properties of the buccal tablets showed consistent tablet weight and excellent friability, with those formulated with Carbopol® polymer meeting the target hardness (Table 1).  Mucoadhesion testing using the IVOR model showed that tablets formulated with Carbopol® 971P NF, 71G NF, and HPMC were retained for at least 6 hours. In contrast, formulations containing sodium alginate or chitosan eroded rapidly and began detaching after just 2 hours, indicating considerably weaker mucoadhesive properties (Table 1 and Figure 2A). Dissolution studies demonstrated that Carbopol®-based tablets released more than 83% of the drug within 6 hours, meeting the predefined performance criteria, whereas HPMC-based tablets did not achieve the required drug release (Table 1). These findings suggested that Carbopol® polymers improved both mucoadhesion and controlled drug release in the buccal delivery system. The incorporation of mucoadhesive polymers in the tablets significantly prolonged adhesion time from minutes to several hours compared to formulations without such polymers (Figure 2B). Furthermore, when compared to commercial products containing carbomer, the optimized buccal tablets formulated with Carbopol® polymers exhibited enhanced retention and integrity (Figure 2B).

Conclusion: This study demonstrated that polymer selection is critical and can significantly impact mucosal retention and drug release characteristics. Among the polymers tested, buccal tablets containing Carbopol® polymers were robust, and exhibited excellent mucoadhesion and sustained drug release. These findings support their use in developing effective, patient-centric oral mucosal drug delivery systems.

References: [1] Zhang et al. “Oral mucosal drug delivery: clinical pharmacokinetics and therapeutic applications,” Clinical Pharmacokinetics, vol. 41, pp. 661-680, 2002.
[2] Brako et al. “Transmucosal drug delivery: prospects, challenges, advances, and future directions,” Expert Opinion on Drug Delivery, vol. 22, no. 4, pp. 525-553, 2025.
[3] Draganoiu et al. “Properties of mucoadhesive polymers and their use in tablets and other dosage forms,” Tablets and Capsules, vol. 14, no. 5, pp. 17-23, 2016.
[4] “Use of amlexanox for the manufacture of a medicament for treating aphthous ulcers”. Patent EP836852B1.
[5] “Stable viscous liquid formulations of amlexanox for the prevent and treatment of mucosal diseases and disorders”. Patent US20020103219A1 .
[6] Smart et al. “A novel in-vitro apparatus for evaluating the mucoadhesion of liquid and semi-solid formulations,” J. Pharm. Pharmacol., vol. 50, p. 167, 1998.

Figure 1. In vitro esophageal retention model used to evaluate mucoadhesive properties.

Table 1. Summary of tablet properties (physical, IVOR and dissolution) from tablets containing different mucoadhesive polymers.

Figure 2. (A) Tablet retention over the course of IVOR test from the tablets containing different mucoadhesive polymers. (B) Tablet retention over the course of IVOR from the Amlexanox tablets and commercial benchmarks.