Nahed Mohamed Sallam, Rania Abdel-Basset Sanad*, Rasha Mohamed kharshoom and Mokhles Abdelfadil Zeneldin Pages 503 - 515 ( 13 )
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.
Clinical evaluation, maltodextrin, pharmacokinetics, pullulan, sublingual films, ZAN spirometry.
Department of Pharmaceutics, National Organization for Drug Control and Research (NODCAR), Cairo, Department of Pharmaceutics, National Organization for Drug Control and Research (NODCAR), Cairo, Egypt; Postal address: Department of Pharmaceutics, National Organization of Drug Control and Research (NODCAR), 6 Abou Hazem Street, Pyramids, Giza, Department of Pharmaceutics, Faculty of Pharmacy, Beni-Sueif University, Beni-Sueif, Department of Chest Diseases, Faculty of Medicine, Al-Azhar University, Damietta