(200ai) Droplet-Coalescence Kinetics for a Non-Newtonian Emulsion Using a Taylor-Couette Shear-Flow Reactor: Characterizing Phase-Separation Risk for a Pharmaceutical Ointment

Authors: 
Sarkar, A., Worldwide Research and Development, Pfizer Inc.
Ketabchi-Haghighat, A., Iowa State University
Vigil, R. D., Iowa State University
Olsen, M., Iowa State University
Topical ointments are complex multiphase fluids, many of which are emulsions comprised of a droplet phase dispersed in a viscous, and often non-Newtonian, continuous phase (e.g., petrolatum or petroleum jelly). The drug substance to be delivered is present in solution within the dispersed droplet phase (propylene glycol in the present case). The physical stability of the ointment after emulsification, i.e., during subsequent processing and packaging, is of great importance—the growth of droplets and the risk of phase separation must be minimized for a viable commercial product.

Although simpler oil-water emulsions have received considerable attention, the behavior of emulsions containing complex, non-Newtonian fluids (e.g., petrolatum) has not been studied in detail. Specifically, the rate kinetics of droplet coalescence and growth are of interest to characterize the risk of phase separation. In the present work, this problem is addressed by studying an emulsion of white petrolatum and propylene glycol as a model ointment using a vertically-oriented, narrow-gap, Taylor-Couette reactor. This reactor allows control over the temperature and mean strain rate, thus allowing emulsion rheology, droplet coagulation, and phase separation to be investigated under varying shear-flow conditions.

Experimental results on the droplet coalescence mechanisms and rates, as well as phase separation, are generated for varying shear-strain rates using digital cameras and image-processing routines. The results demonstrate that the risk of phase separation increases with increasing strain rate—this is quantified as a characteristic phase-separation time scale. Finally, the experimental results are linked back to the commercial-scale process to show that the operating conditions of the actual manufacturing process are indeed robust with a low risk of phase separation.