Hyaluronic-benzydamine oromucosal films outperform conventional mouth rinse in ulcer healing

Abstract

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.