The physical stability of a prototypical pharmaceutical topical ointment, consisting primarily of an emulsion of propylene glycol droplets dispersed in a continuous white petrolatum medium, was studied with regard to droplet size growth and phase separation when the ointment undergoes heating or fluid shear. To investigate the effects of shear, the ointment at 32 °C was sheared using a transparent, narrow-gap, temperature-controlled Taylor-Couette flow apparatus operated under laminar flow conditions which provided approximately uniform shear rates. Optical methods based on microscopy were used to obtain in-situ, time-dependent propylene glycol droplet size distributions, while a wide-field lens and camera were simultaneously used to detect gross phase separation as the ointment was sheared. Microscopy was also used to observe and quantify ointment stability via analysis of droplet size evolution in the absence of fluid shear for a range of elevated temperatures. For a quiescent ointment, it was observed that the dispersed propylene glycol droplets do not exhibit any appreciable growth over a period of one month and temperatures as high as 45 °C. In contrast, fluid shear imposed at 32 °C was observed to cause rapid growth of dispersed phase droplets and the onset of large phase separated regions on time scales ranging between a few minutes to approximately half an hour for fluid strain rates ranging between 5.5 and 50 s-1, respectively. The experimental results from the lab-scale Couette flow apparatus were used to evaluate the risk of phase separation during commercial-scale manufacturing.
Keywords: Coalescence; Dispersion; Droplets; Emulsion; Phase separation; Stability; Topical ointment.
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