DEVELOPMENT AND CHARACTERIZATION OF GLYCYRRHIZIN-LOADED BUCCAL FILM-O-SPRAY: A NOVEL APPROACH TO RECURRENT APHTHOUS STOMATITIS THERAPY

AYESHA SYED; PREETI KARWA; SOHAL MALLICK; PRITHIVIRAJAN S.

doi:10.22159/ijap.2025v17i6.55216

Authors

AYESHA SYED Al-Ameen College of Pharmacy, Department of Pharmaceutics, Rajiv Gandhi University of Health sciences, Bengaluru, Karnataka, India
PREETI KARWA Al-Ameen College of Pharmacy, Department of Pharmaceutics, Rajiv Gandhi University of Health sciences, Bengaluru, Karnataka, India https://orcid.org/0000-0002-3367-5237
SOHAL MALLICK Al-Ameen College of Pharmacy, Department of Pharmaceutics, Rajiv Gandhi University of Health sciences, Bengaluru, Karnataka, India https://orcid.org/0009-0003-9700-3426
PRITHIVIRAJAN S. Al-Ameen College of Pharmacy, Department of Pharmaceutics, Rajiv Gandhi University of Health sciences, Bengaluru, Karnataka, India

DOI:

https://doi.org/10.22159/ijap.2025v17i6.55216

Keywords:

Recurrent aphthous stomatitis, Glycyrrhizin, Film-forming spray, Box-behnken design, Mucoadhesive system

Abstract

Objective: Recurrent aphthous stomatitis (RAS), affecting 5–50% of the population, is characterized by painful oral ulcers. Conventional therapies often lead to side effects, drug resistance, and secondary infections, underscoring the need for safer and more effective alternatives. This study aimed to develop a glycyrrhizin-based film-forming spray (FFS_GLY) to enhance mucosal drug delivery, prolong retention, and provide rapid relief from oral ulcers.

Methods: A 3³ Box–behnken design was employed to optimize the concentrations of HPMC-E15, Eudragit-S100, and propylene glycol (PG), considering drying time and viscosity as dependent variables. The optimized formulation (F4) was evaluated for physicochemical properties, mucoadhesion, and mucosal drug retention. Each actuation of the spray was standardized to deliver 3 mg of glycyrrhizin. Preclinical efficacy was assessed in wistar rats with acetic acid–induced oral ulcers, supported by histopathological analysis.

Results: The optimized F4 formulation demonstrated a drying time of 75.12±0.05 seconds and viscosity of 19.28±0.019 cPs. It exhibited strong mucoadhesive strength (577.5±0.016 dynes/cm²; 0.05775 N/cm²) and sustained mucosal retention (6.105 mg/cm²) for up to 24 h. Consistent dose delivery was achieved with each spray actuation. In vivo studies showed significant reduction in ulcer diameter compared to controls, while histopathological evaluation confirmed enhanced epithelial regeneration and angiogenesis.

Conclusion: The developed FFS_GLY formulation demonstrated favourable physicochemical characteristics, excellent mucosal retention, and significant therapeutic efficacy in preclinical models. These findings establish FFS_GLY as a safe, effective, and promising alternative for the management of recurrent aphthous stomatitis.

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