Oral mucositis is an ulcerative inflammation that is commonly encountered in patients receiving radio- and chemotherapy as an acute side effect. Local benzydamine (Bnz) application suppresses inflammation, while hyaluronic acid (HA) aids ulcer healing. In this study, Bnz-HA, a triple-layer oromucosal film, was developed for fast localized treatment of oral mucositis, compared to conventional formulations, with the aim to prolong Bnz retention onto the affected area and enhance its therapeutic efficacy by HA incorporation. The Bnz-HA films comprised a mucoadhesive-layer, containing HA and HPMC 4000, that adheres to the oral mucosa and controls Bnz release from the middle drug-layer, which was, in turn, adhered to a backing-layer containing Eudragit RS and allowing unidirectional drug release. Similarly, Bnz films were prepared omitting the HA addition. The films were characterized for their mucoadhesion, swelling capacity and in vitro drug release. The extent and duration of ulcer healing after 5 days film application were recorded in vivo using oral ulcer rabbit model. Bnz-HA and Bnz films showed strong mucoadhesion, maximum swelling after 2 h and a controlled drug release over 12 h. However, the incorporation of HA in Bnz-HA films significantly enhanced ulcer healing, outperforming the Bnz film and Tantum-Verde® mouth rinse. Conclusively, Bnz-HA films control Bnz release, reduce the dosing frequency and achieve rapid ulcer healing, hence being a promising delivery system outperforming conventional oral rinse.

口腔粘膜炎是一种溃疡性炎症，在接受放疗和化疗作为急性副作用的患者中很常见。局部使用苄达明 (Bnz) 可抑制炎症，而透明质酸 (HA) 有助于溃疡愈合。在这项研究中，与常规制剂相比，Bnz-HA 是一种三层口腔粘膜膜，用于快速局部治疗口腔粘膜炎，目的是延长 Bnz 在患处的保留时间，并通过掺入 HA 提高其治疗效果。Bnz-HA 薄膜包含一个含有 HA 和 HPMC 4000 的粘膜粘附层，粘附在口腔粘膜上并控制 Bnz 从中间药物层释放，中间药物层又粘附在含有 Eudragit RS 和允许单向药物释放。相似地，Bnz 薄膜是在不添加 HA 的情况下制备的。这些薄膜的特征在于它们的粘膜粘附、溶胀能力和体外药物释放。使用口腔溃疡兔模型在体内记录贴膜5天后溃疡愈合的程度和持续时间。Bnz-HA 和 Bnz 薄膜显示出强烈的粘膜粘附、2 小时后最大肿胀和 12 小时后药物释放受控。然而，在 Bnz-HA 薄膜中加入 HA 显着增强了溃疡愈合，优于 Bnz 薄膜和 Tantum-Verde® 漱口水。总之，Bnz-HA 薄膜控制 Bnz 释放，降低给药频率并实现溃疡快速愈合，因此是一种优于传统口腔冲洗液的有前途的给药系统。