Development of alendronate niosomal delivery system for gastrointestinal permeability improvement

Abstract

In this study, the influences of surfactant types, the molar ratio of surfactant and cholesterol, and the molar ratio of drug load and total lipids on the size, zeta potential and drug entrapment efficiency of niosomes were statistically evaluated using a central composite design. Alendronic acid, a bisphosphonate compound was used to study. Stability, in vitro drug release and gastrointestinal permeability improvement of alendronate niosomal dispersion were also studied. The results showed that surfactant types, molar ratios of surfactant to cholesterol and molar ratios of drug load to total lipids had a significant effect on particle size, zeta potential and drug entrapment efficiency of niosomes (P < 0.05). The obtained niosomes were of a unilamellar spherical shape with negative zeta potential values. The niosomes prepared from Span 60 were larger and more entrapment efficient than those prepared from Span 20. In addition, the decrease of molar ratios of Spans and cholesterol resulted in the increase of zeta potential. The particle size and drug entrapment efficiency decrease when the molar ratio of Spans and cholesterol was decreased. Moreover, increase of drug load and total lipid molar ratio resulted in the decrease of zeta potential. However, particle size and drug entrapment efficiency could be increased with increasing molar ratio of drug loading and total lipid. Niosomes prepared from Span 60 showed a slower release rate than those prepared from Span 20. In the stability study, when stored at 4 °C for 90 days, only niosomes prepared from Span 20 have no significant change in particle size, zeta potential and the percentage of drug entrapment. The permeation of alendronate niosomes across Caco-2 cells monolayer showed that the average apparent permeability of alendronic acid from the niosomal dispersion prepared from Span 20 and Span 60 were significantly greater than that of the drug solution. This study revealed that niosomal dispersion can improve the oral bioavailability of alendronic acid.