Development of Salbutamol Sulphate Sublingual Films in Pullulan Matrix for Enhanced Bioavailability & Clinical Efficacy.

Background: Salbutamol sulphate (SS) is a model short-acting β2-adrenergic receptor agonist used for the relief of bronchospasm having poor bioavailability (50%) due to its extensive first-pass effect.

Objective: Formulation of SS as fast dissolving sublingual films (FDSFs) using a biocompatible and biodegradable Pullulan polymer to bypass its metabolism in liver and offers a fast relieve of asthma.

Method: Films were prepared by solvent casting technique adopting 32 factorial design to study the effect of two independent variables namely; polymer type (HPMC E5, Pullulan, and L-HPC) and polymer to Maltodextrin ratio (3:0, 3:1 or 5:1). Films physicomechanical properties, disintegration time and in-vitro dissolution of the prepared formulations were evaluated.

Results: Formula F3 containing Pullulan with Maltodextrin in a ratio 3:1 has the least disintegration time (26±2.6 seconds) and the highest dissolution rate (100%±0.5%) after four minutes. Pharmacokinetic study of the optimum formula F3 in healthy human volunteers revealed a shorter tmax (0.75±0.25 hour) compared to Ventolin® tablet 2 mg (2.1±0.37 hour). Clinical evaluation of F3 in 14 male asthmatic patients using ZAN Spirometry showed clinical improvement in lung function parameters when compared with Ventolin® tablets.

Conclusion: FDSFs significantly improved the bioavailability of SS and resulted in dramatic improvement in its clinical efficacy.