Design and evaluation of aspirin-loaded water-in-oil-in-water submicron multiple emulsions generated using two-stage ultrasonic cavitational emulsification technique

The main goal of the present work was to develop a novel aspirin containing water-in-oil-in-water (W/O/W)-type submicron multiple emulsions via two-stage ultrasound cavitational emulsification using Span 80 and Cremophor EL as lipophilic and hydrophilic emulsifiers for the formation of primary and secondary emulsions, respectively. Effect of the following parameters, i.e. concentration of emulsifiers, ultrasonic amplitude and second sonication period on the mean droplet diameter, polydispersity index, droplet size stability and drug entrapment efficiency was studied. The osmotic behavior of the ultrasonically prepared multiple emulsions was also studied with different glucose concentrations in the inner and outer aqueous phases. The presence of gelatin played an important role in preventing interdroplet coalescence via formation of interfacial rigid film. Core shell type of multiple droplets with mean droplet diameter of around 400nm was produced using 1.25%w/w Span 80 and 0.5%w/w Cremophor EL. The experimental results have shown that the long-term stability of the W/O/W multiple emulsions is significantly improved with the addition of both 0.5%w/w of glucose and 1%w/w of gelatin in the inner phase. This investigation has clearly proved that the use of ultrasound cavitation is an efficient yet promising approach in the generation of stable and uniform submicron multiple emulsions of aspirin.