Omeprazole (OME) is employed for treating ulcer in children, but is unstable and exhibits first pass metabolism via the oral route. This study aimed to stabilize OME within mucoadhesive metolose (MET) films by combining cyclodextrins (CD) and l-arginine (l-arg) as stabilizing excipients and functionally characterizing for potential delivery via the buccal mucosa of paediatric patients. Polymeric solutions at a concentration of 1% w/w were obtained by dispersing the required weight of metolose in 20% v/v ethanol as solvent at a temperature of 40 °C using polyethylene glycol (PEG 400) (0.5% w/w) as plasticizer. The films were obtained by drying the resulting polymer solutions at in an oven at 40 °C. Textural (tensile and mucoadhesion) properties, physical form (differential scanning calorimetry (DSC), X-ray diffraction (XRD) and Fourier transform infrared (FTIR) spectroscopy), residual moisture content (thermogravimetric analysis (TGA)) and surface morphology (scanning electron microscopy (SEM)) were investigated. Optimized formulations containing OME, CDs (β or γ) and l-arg (1:1:1) were selected to investigate the stabilization of the drug. The DSC, XRD, and FTIR showed possible molecular dispersion of OME in metolose film matrix. Plasticized MET films containing OME:βCD:l-arg 1:1:1 were optimum in terms of transparency and ease of handling and therefore further functionally characterized (hydration, mucoadhesion, in vitro drug dissolution and long term stability studies). The optimized formulation showed sustained drug release that was modelled by Korsmeyer⁻Peppas equation, while the OME showed stability under ambient temperature conditions for 28 days. The optimized OME loaded MET films stabilized with βCD and l-arg have potential for use as paediatric mucoadhesive buccal delivery system, which avoids degradation in the stomach acid as well as first pass metabolism in the liver.
Keywords: ">l-arginine; buccal mucosa drug delivery; cyclodextrins; films; mucoadhesive polymer; omeprazole; paediatric.