Treatment of Radiation-Induced Oral Mucositis Using a Novel Accepted Taste of Prolonged Release Mucoadhesive Bi-medicated Double-Layer Buccal Films

The aim of this study was to develop a novel double-layer bi-medicated prolonged release mucoadhesive buccal film (MBF) containing lidocaine hydrochloride (LC) and diclofenac potassium (DK). The ultimate goal of the prepared system is the treatment of radiation-induced oral mucositis pain with improved patient acceptance. MBFs were prepared using 3 x 2(2) randomized full factorial design for film optimization. Nanoemulsion system (NES) was used to mask DK bitter taste. The prepared films were characterized, viz thickness, mass uniformity, surface pH, folding endurance, swelling studies, ex vivo bioadhesive strength, in vitro drug release, and ex vivo permeation. The in vivo evaluation was carried out by testing the anti-inflammatory and analgesic activities on rats followed by a clinical study on patients to prove their acceptance. The optimized MBF composed of 10% w/w HPMC-4KM, 50 mg LC, and 50 mg DK-NES was selected due to prolonged in vitro drug release pattern and ex vivo permeability (95.24 +/- 2.14 and 93.48 +/- 3.24% in 6 h, respectively). MBF exposed a strong anti-inflammatory effect from 61 to 87% inhibition with a strong analgesic effect when compared to DK (R) and LC (R), respectively. The clinical study revealed that films were accepted by the patients, and the presence of LC on the outer side helped in pain feeling reduction while DK-NES in the inner side facilitated in rapidly relieving the inflammation effect.