Formulation development and characterization of peptide-based spray-forming in situ gel for enhanced buccal permeation and improved stability.

AIM: To develop an in situ gelling buccal spray to improve the permeation and stability of reduced glutathione through the buccal mucosa without using ascorbic acid as an antioxidant. MATERIALS AND METHODS: Glutathione, a hydrophilic thiol peptide classified as a Biopharmaceutics Classification System (BCS) class III drug, exhibits poor oral bioavailability due to limited permeability, enzymatic degradation by gamma-glutamyl transferase, and instability in aqueous environments. The formulation was optimized based on gelling time and glutathione stability and evaluated for spray pattern, in situ gelling time, volume expansion, gel rheology, gel degradation, pH, drug content, in vitro buccal mucosa permeation, and stability. RESULTS: The optimized formulation was transparent and formed an in situ gel within 2-6 min. Liquid chromatography-mass spectrometry (LC-MS) analysis confirmed approximately 98% drug content per 0.2 mL actuation and demonstrated improved stability at 4°C compared with the plain drug solution. In vitro permeation studies showed an approximately 10-fold increase in permeability flux, while stability studies confirmed enhanced stability for more than 1 month under refrigerated conditions. CONCLUSION: The developed in situ gelling buccal spray significantly improved the stability and buccal permeation of reduced glutathione, demonstrating its potential as an effective noninvasive delivery system.