ABSTRACT
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.
Subject(s)
Microscopy , Petrolatum , Emulsions , Ointments , TemperatureABSTRACT
A technique for visualizing and quantifying reactive mixing for laminar and turbulent flow in a microscale chemical reactor using confocal-based microscopic laser induced fluorescence (confocal µ-LIF) was demonstrated in a microscale multi-inlet vortex nanoprecipitation reactor. Unlike passive scalar µ-LIF, the reactive µ-LIF technique is able to visualize and quantify micromixing effects. The confocal imaging results indicated that the flow in the reactor was laminar and steady for inlet Reynolds numbers of 10, 53, and 93. Mixing and reaction were incomplete at each of these Reynolds numbers. The results also suggested that although mixing by diffusion was enhanced near the midplane of the reactor at Rej = 53 and 93 due to very thin bands of acidic and basic fluid forming as the fluid spiraled towards the center of the reactor, near the top, and bottom walls of the reactor, the lower velocities due to fluid friction with the walls hindered the formation of these thin bands, and, thus, resulted in large regions of unmixed and unreacted fluid. At Rej = 240, the flow was turbulent and unsteady. The mixing and reaction processes were still found to be incomplete even at this highest Reynolds number. At the reactor midplane, the flow images at Rej = 240 showed unmixed base fluid near the center of the reactor, suggesting that just as in the Rej = 53 and 93 cases, lower velocities near the top and bottom walls of the reactor hinder the mixing and rection of the acidic and basic streams. Ensemble averages of line-scan profiles for the Rej = 240 were then calculated to provide statistical quantification of the microscale mixing in the reactor. These results further demonstrate that even at this highest Reynolds number investigated, mixing and reaction are incomplete. Visualization and quantification of micromixing using this reactive µ-LIF technique can prove useful in the validation of computational fluid dynamics models of micromixing within microscale chemical reactors.
ABSTRACT
Confined impinging-jets reactors (CIJR) offer many advantages for rapid chemical processing at the microscale in applications such as precipitation and the production of organic nanoparticles. It has been demonstrated that computational fluid dynamics (CFD) is a promising tool for "experiment-free" design and scale-up of such reactors. However, validation of the CFD model used for the microscale turbulence applications requires detailed experimental data on the unsteady flow, the availability of which has until now been very limited. In this work, microscopic particle-image velocimetry (microPIV) techniques were employed to measure the instantaneous velocity field for various Reynolds numbers in a planar CIJR. In order to illustrate the validation procedure, the performance of a particular CFD model, the two-layer k-epsilon model, was evaluated by comparing the predicted flow field with the experimental data. To our knowledge, this study represents the first attempt to directly measure and quantify velocity and turbulence in a microreactor and to use the results to validate a CFD model for microscale turbulent flows.
