Development of Salbutamol Sulphate fast disintegrating sublingual tablets with enhanced bioavailability and improved clinical efficacy for potential treatment of asthma

Abstract

Salbutamol Sulphate (SS) as a model bronchodilator drug undergoes first pass metabolism in liver, which has an oral bioavailability of only 50% of the administrated dose. Thus, the aim of this study was to attain rapid absorption and improved bioavailability, with subsequent immediate rapid onset of pharmacological effect. This work introduces a new design of SS fast disintegrating sublingual tablets (FDSTs) using a full factorial design (23) with three independent variables: the type of superdisintegrant (Ac-di-sol or Polyplasdone-XL), its concentration (3% or 5%w/w) and the binder type (Avicel PH101 or PEG6000). The formula T7 containing Polyplasdone-XL (5%w/w) with Avicel PH101 (10%w/w) had the least disintegration time (12.83 ± 0.7 s) and the highest dissolution rate (100 ± 2.6%), hence was selected for pharmacokinetic study in human volunteers. T7 showed Cmax of 19.36 ± 2.64 μg/ml, tmax of 1.33 ± 0.24 h; the mean AUC(0-8) was found to be 75.059 ± 7.55 μg h/ml and the AUC (0-∞) of 90.554 ± 8.027 μg h/ml. The relative bioavailability of T7 was 129.92% when compared to Ventolin® tablets. The clinical evaluation of T7 in fourteen asthmatic patients showed significant difference in forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and peak expiratory flow rate (PEFR) when compared to Ventolin® tablets using ZAN spirometry.