Novel benzydamine hydrochloride and chlorhexidine gluconate loaded bioadhesive films for local treatment of buccal infections

Benzydamine hydrochloride (BZD), chlorhexidine gluconate (CHG) or their combination are frequently used as liquid dosage forms for the local treatment of buccal fungal and bacterial infections. However, the short residence time of liquid formulations in the oral cavity and the necessity of frequent applications limit the treatment effectiveness. To this end, CHG and BZD loaded buccal bioadhesive films, which remain at the application site longer than the liquid forms, were developed using hydroxypropyl methyl cellulose (HPMC) (2-4%) and chitosan (2-4%). The swelling studies revealed that P1, P3 and P4 films remained without loss of their integrity in the buccal medium for more than 2 h compared to other developed films. Bioadhesion studies performed with a texture analyser showed that P3 (2% chitosan+4% HPMC) yielded the greatest bioadhesion work (0.403 +/- 0.027 mJ/cm2). The in vitro drug release from buccal films was evaluated by the paddle over disk method. Ex vivo penetration and permeation studies demonstrated that CHG did not pass through bovine buccal mucosa, whereas 4.82-27.35 mu g/cm2 of BZD passed through the mucosa. However, the amount of BZD and CHG accumulated in the mucosa ranged between 127.86 and 190.76 mu g/cm2 and 54.09-94.76 mu g/cm2, respectively. Additionally, both penetration and antimicrobial activity studies revealed that the buccal films were more effective than the marketed spray product. The obtained data demonstrate that the developed films are promising candidates for the buccal delivery of CHG and BZD.