Estimation of Storage Stability of Aqueous Microbubble Suspensions

The aqueous suspensions of gaseous microbubbles are currently being used as contrast enhancing agents for ultrasonic imaging and as potential vehicles for targeted drug delivery. The storage stability of microbubble suspensions is very important as for any possible application of microbubbles, a stable microbubble suspension is needed. A stable microbubble suspension is a suspension for which there is no drastic change in concentration (number of microbubbles/mL of storage solution) and microbubble size distribution during the period of storage. To characterize storage stability, half-life of the microbubble suspensions, which is the time required for the microbubble concentration (#/mL) to decrease by 50% during storage, was estimated using a simple model. The proposed model estimates the storage stability of aqueous microbubble suspensions and effect of material properties on their storage stability. It takes into account an inter-bubble mass transfer and combines it with a population balance equation to account for a change in concentration (#/mL) as well as size and size distribution of microbubbles in the aqueous suspensions. The calculations have been performed for microbubbles made of three gases, namely oxygen (O<inf>2</inf>), sulphur hexafluoride (SF<inf>6</inf>) and perfluorobutane (PFB). The variation in storage stability of microbubble suspensions was examined by varying microbubble shell properties such as shell elasticity, surface tension and shell resistance as well as the other parameters such as viscosity of the storage medium and the initial size distribution of the microbubbles. The analysis of the results show that, among the shell properties studied, the shell resistance influenced the suspension stability the most and shell elasticity influenced the stability the least. Similarly, a gas with the lower liquid phase diffusivity and lower Ostwald coefficient results in a stable microbubble suspension. Also, higher viscosity of storage solution and microbubbles with larger sizes tend to increase the storage stability. Overall, the increase in the total resistance (combination of shell resistance and resistance in the storage solution) to mass transfer of a gas increases the storage stability of the microbubble suspensions.