Bi-Layered Tablets as a Novel Platform for Wound Healing and Synergistic Combination Therapy

Effective management of acute wounds, particularly those caused by burns and trauma, remains a significant clinical challenge. Conventional formulations, such as ointments, creams, and hydrogels, often face challenges related to stability, portability, and patient compliance. To address these limitations, we developed a novel bi-layered skin tablet system using direct compression for immediate application to topical wounds. The upper protective layer contains konjac glucomannan as a gelling agent and oleic acid as a permeability enhancer. The lower therapeutic layer includes a synergistic combination of clindamycin hydrochloride (CLC), benzalkonium chloride (BKC), and recombinant human mitsugumin 53 (rhMG53), a membrane repair protein. rhMG53 was repurposed for acute wound healing at a reduced dosage to maintain therapeutic efficacy while improving cost efficiency. The formulation was optimized to achieve controlled release of rhMG53 for wound repair and of CLC and BKC for antibacterial activity. The synergistic interaction between CLC and BKC (Index 1.2) enhanced broad-spectrum antibacterial efficacy. The prepared tablets underwent in-vitro testing for hardness, swelling index, content uniformity, drug release, and stability. The rhMG53 containing formulation demonstrated consistent drug loading (98.5%, RSD < 6%), prolonged release, and effective wound healing in cell-based tests. The tablet form improves portability, stability, and ease of application compared with conventional remedies. This bi-layered skin tablet system represents a promising therapeutic strategy for acute wound management, particularly in emergency and military settings where lightweight, ready-to-use treatments are critically needed.