5ch The Impact of Microstructure on the Gravitationally-Induced Phase Separation in Concentrated Vesicle Dispersions

Arun Ramachandran, Chemical Engineering, University of California at Santa Barbara, 3235 Engineering II, Santa Barbara, CA 93106

It is well known that most processes for synthesizing vesicles such as lipid film hydration, ethanolic lipid injection in aqueous buffers and reverse phase evaporation result in vesicles that are in kinetically trapped states. As such a concentrated vesicle suspension attempts to shift towards some equilibrium, the size and lamellarity distributions of the vesicles evolve with time. The changes in these distributions have a special implication for non-neutrally buoyant vesicle systems in that a shift towards larger and denser vesicles leads to a greater propensity for them to separate from the suspending fluid on account of gravity. Since the shelf-life expected of vesicle based formulations can be as long as a couple of years, the knowledge of the time scale of coarsening of vesicle dispersions is extremely valuable.

The time required to observe gravitationally-induced separation in vesicle dispersions depends broadly on the following two factors:

(a) The exact procedure used to synthesize the vesicle dispersion is crucial in determining the long term stability of vesicle dispersions, since this establishes the initial size and lamellarity distributions of the vesicles. Poorly designed synthesis techniques which produce large and multilamellar vesicles at the outset lead to high rise velocities of the vesicles, and consequently, shorter separation times. A popular method of preparing a concentrated vesicle suspension is by mixing a concentrated solution of lipids in ethanol with an aqueous buffer. This technique is particularly attractive in the industry because of its capability of being scaled up into a continuous process. However, there is no information in the literature on the size and lamellarity distributions that result from this mixing process for concentrated systems. There are several important process variables that determine these distributions: the properties of the constituent surfactants, the concentration of the ethanolic lipid solution, the flow rates of the aqueous and ethanolic lipid solutions, the design of the mixing unit and the operating temperature. The role of each of these factors will be discussed in the poster.

(b) Any mechanism that leads to bigger and/or more multilamellar vesicles can play an important role in the phase separation process. Even though the vesicles may be small right after synthesis, such mechanisms may quickly produce larger and denser vesicles which gravitationally separate more easily. The usual suspects for vesicle growth are aggregation, such as produced by the presence of a suitable non-adsorbing polymer, and fusion, and these have been addressed in some detail in the literature. However, in our studies of the evolution of these vesicle suspensions, there is evidence of mechanisms such as encapsulation and deflation/invagination leading to larger and denser vesicles, and these new mechanisms will be presented.

The results and questions posed in the poster provide plenty of scope for future experimental and theoretical work in this area. These will be briefly outlined in the poster.