Optimization and comparison of unidirectional lidocaine-loaded buccal patch with the articaine-loaded buccal patch to reduce injection pain and increment of patients' compliance in dental procedures: A double-blind randomized controlled trial.

Introduction: Nervous patients often postpone dental visits until they are in severe pain, exacerbating anxiety. Buccal patches provide a noninvasive method of delivering drugs between the upper gum and cheek, offering local and systemic effects. Prior research has demonstrated the effectiveness, safety, and reliability of topical lidocaine or articaine patches for oral anesthesia. Consequently, this study aimed to develop a three-layered buccal drug delivery system for topical anesthetics. Methods: The first step was preparing and optimizing lidocaine-loaded three-layer patches using Design-expert software. The effects of ethylcellulose, Eudragit, and carbopol concentrations were investigated on patch characteristics, including mucoadhesion, Young's modulus, and Elongation-at-break. Subsequently, patches were fabricated according to the optimized formulation determined by the software, and their efficacy was studied in a randomized, double-blind clinical trial. Participants received either lidocaine or articaine-loaded compared with placebo in a split-mouth study. They evaluated their pain levels using the Visual Analogue Scale (VAS), and the onset and duration of action were recorded for each treatment. Results: According to the results, increasing ethyl cellulose and Eudragit concentrations improved mucoadhesion force (p < 0.05) while increasing ethyl cellulose and reducing Eudragit concentrations increased Young's modulus (p < 0.05). Increasing Carbopol and decreasing Eudragit concentrations also raised elongation at break significantly in the patch (p < 0.05). Treatment with lidocaine-loaded patches resulted in lower VAS scores and faster onset of action in patients than articaine-loaded patches. However, the duration of the effect was longer in the former(p < 0.001). Conclusion: Based on the responses' analysis, the formulation of the 3-layered buccal patch was optimized. This formulation comprised 4.72 % ethyl cellulose, 2 % Carbopol, and 5 % eudragit. Clinical evaluation results showed that loading the optimized formulation with lidocaine was more efficient in controlling the injection pain than articaine. Trial registration: This trial was prospectively registered with irct.behdasht.gov.ir (registration number: IRCT20210118050067N2) on Aug 19, 2022.