Salbutamol sulphate (SS) is a widely prescribed β2 agonist for different respiratory disorders. However, its short plasma half-life and poor oral bioavailability strongly limit its compliance. This study targeted formulating SS in nanostructured lipid carriers (SS-NLCs) embedded in a buccal mucoadhesive film to enhance bioavailability and sustain release through an easy route of administration aiming to improve patient compliance and reduce dose-related side effects. SS-NLCs were prepared using glycerol monostearate (GMS), Labrasol® oil, and poloxamer 407 utilizing a full 23 factorial design. Eight SS-loaded NLCs formulations were evaluated for particle size distribution, zeta potential, and entrapment efficiency. The optimum formula selected according to design expert® statistical analysis, was subsequently incorporated in a polymeric buccal mucoadhesive film and subjected to in vitro and in vivo characterization. The optimum SS-NLCs showed a mean particle size of 119.1 ± 1.28 nm, polydispersity index of 0.248 ± 0.023, zeta potential of - 40.9 ± 0.47 mV, and entrapment efficiency of 68.20 ± 2.05 % with apparent controlled release. Casting SS-NLCs in a mucoadhesive polymeric mixture resulted in a smooth strong film with a prolonged in vitro drug release duration reaching 10 h. In vivo, buccal application of the formulated film showed significantly higher Cmax (107.53 ± 5.20 ng/ml) and delayed Tmax to 4 h with improving the bioavailability of SS by 4.10 folds compared to oral SS solution. Consequently, the buccal polymeric mucoadhesive film of SS-NLCs holds promise as an alternative route for sustained release, enhancing bioavailability, and improving therapeutic efficacy in treating respiratory disorders.
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