Impact of osmotic pressure and gelling in the generation of highly stable single core water-in-oil-in-water (W/O/W) nano multiple emulsions of aspirin assisted by two-stage ultrasonic cavitational emulsification

The present investigation focuses in investigating the effect of osmotic pressure, gelling on the mean droplet diameter, polydispersity index, droplet size stability of the developed novel Aspirin containing water-in-oil-in-water (W/O/W) nano multiple emulsion. The aspirin-loaded nano multiple emulsion formulation was successfully generated using two-stage ultrasonic cavitational emulsification which had been reported in authorʹs previous study. The osmotic behavior of ultrasonically prepared nano multiple emulsions were also examined with different glucose concentrations both in the inner and outer aqueous phases. In addition, introducing gelatin into the formulation also observed to play an important role in preventing the interdroplet coalescence via the formation of interfacial rigid film. Detailed studies were also made on the possible mechanisms of water migration under osmotic gradient which primarily caused by the permeation of glucose. Besides, the experimental results have shown that the interfacial tension between the two immiscible phases decreases with varying the composition of organic phase. Although the W/O/W emulsion prepared with the inner/outer glucose weight ratio of 1–0.5% (w/w) showed an excellent droplet stability, the formulation containing 0.5% (w/w) glucose in the inner aqueous phase appeared to be the most stable with minimum change in the mean droplet size upon one-week storage period. Based on the optimization, nano multiple emulsion droplets with the mean droplet diameter of around 400 nm were produced using 1.25% (w/w) Span 80 and 0.5% Cremophore EL. Overall, our investigation makes a pathway in proving that the use of ultrasound cavitation is an efficient yet promising approach in the generation of stable and uniform nano multiple emulsions and could be used in the encapsulation of various active pharmaceutical ingredients in the near future.