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

Abstract

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 × 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® and LC®, 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.

The Application of 3D Printing in the Formulation of Multilayered Fast Dissolving Oral Films

“…It should be noted that manufacture of layered oral films have been achieved previously by employing solvent casting method. [30][31][32] However, the films manufactured by the 3D method (in particular mesh designs) had more thickness uniformity than layered films prepared by the solvent casting method. 32 In this study, we found that paracetamol was stable at extrusion temperature of 130C (for formulations containing PVA) and printing temperature of 190C (films containing PVA).…”

Oromucosal films: from patient centricity to production by printing techniques

“…Another example is the development of a bi-medicated bilayer MBF. This MBF contains lidocaine in the outer side and diclofenac in the inner side and is intended for the treatment of radiationinduced oral mucositis [65].…”

World Workshop on Oral Medicine VII: Non‐opioid pain management of head and neck chemo/radiation‐induced mucositis: A systematic review

“…() included burning and vomiting, and this may negatively impact patients undergoing head and neck cancer treatment due to further mucosal irritation and subsequent discomfort. A study (Abo Enin, El Nabarawy, & Elmonem, ) reports on the development of a novel double‐layer, bi‐medicated, prolonged release mucoadhesive buccal film containing diclofenac and lidocaine; clinical trials on the effectiveness of this intervention are required, given that NSAIDs are generally considered ulcerogenic and are associated with an increased risk of adverse cardiovascular events.…”