We consider the viscous limit of a plane channel miscible displacement flow of two generalized Newtonian fluids when buoyancy is significant. The channel is inclined close to horizontal. A lubrication/thin-film approximation is used to simplify the governing equations and a semi-analytical solution is found for the flux functions. We show that there are no steady travelling wave solutions to the interface propagation equation. At short times the diffusive effects of the interface slope are dominant and there is a flow reversal, relative to the mean flow. We are able to find a short-time similarity solution governing this initial counter-current flow. At longer times the solution behaviour can be predicted from the associated hyperbolic problem (where diffusive effects are set to zero). Each solution consists of a number N ≥ 1 of steadily propagating fronts of differing speeds, joined together by segments of interface that are stretched between the fronts. Diffusive effects are always present in the propagating fronts. We explore the effects of viscosity ratio, inclinations and other rheological properties on the front height and front velocity. Depending on the competition of viscosity, buoyancy and other rheological effects, it is possible to have single or multiple fronts. More efficient displacements are generally obtained with a more viscous displacing fluid and modest improvements may also be gained with slight positive inclination in the direction of the density difference. Fluids that are considerably shear-thinning may be displaced at high efficiencies by more viscous fluids. Generally, a yield stress in the displacing fluid increases the displacement efficiency and yield stress in the displaced fluid decreases the displacement efficiency, eventually leading to completely static residual wall layers of displaced fluid. The maximal layer thickness of these static layers can be directly computed from a one-dimensional momentum balance and indicates the thickness of static layer found at long times.

Development of an oral in vivo predictive dissolution medium for acid drugs with a pKa in the physiological range (e.g., Biopharmaceutics Classification System Class IIa) requires transport analysis of the complex in vivo CO2 /bicarbonate buffering system. In this report, we analyze this buffer system using hydrodynamically defined rotating disk dissolution. Transport analysis of drug flux was predicted using the film model approach of Mooney et al based on equilibrium assumptions as well as accounting for the slow hydration reaction, CO2 + H2 O → H2 CO3 . The accuracy of the models was compared with experimentally determined results using the rotating disk dissolution of ibuprofen, indomethacin, and ketoprofen. The equilibrium and slow hydration reaction rate models predict significantly different dissolution rates. The experimental results are more accurately predicted by accounting for the slow hydration reaction under a variety of pH and hydrodynamic conditions. Although the complex bicarbonate buffering system requires further consideration given its dynamic nature in vivo, a simplifying irreversible reaction (IRR) transport analysis accurately predicts in vitro rotating disk dissolution rates of several carboxylic acid drugs. This IRR transport model provides further insight into bicarbonate buffer and can be useful in developing more physiologically relevant buffer systems for dissolution testing.

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Bicarbonate is the main buffer in the small intestine and it is well known that buffer properties such as pKa can affect the dissolution rate of ionizable drugs. However, bicarbonate buffer is complicated to work with experimentally. Finding a suitable substitute for bicarbonate buffer may provide a way to perform more physiologically relevant dissolution tests. The dissolution of weak acid and weak base drugs was conducted in bicarbonate and phosphate buffer using rotating disk dissolution methodology. Experimental results were compared with the predicted results using the film model approach of (Mooney K, Mintun M, Himmelstein K, Stella V. 1981. J Pharm Sci 70(1):22-32) based on equilibrium assumptions as well as a model accounting for the slow hydration reaction, CO2 + H2 O → H2 CO3 . Assuming carbonic acid is irreversible in the dehydration direction: CO2 + H2 O ← H2 CO3 , the transport analysis can accurately predict rotating disk dissolution of weak acid and weak base drugs in bicarbonate buffer. The predictions show that matching the dissolution of weak acid and weak base drugs in phosphate and bicarbonate buffer is possible. The phosphate buffer concentration necessary to match physiologically relevant bicarbonate buffer [e.g., 10.5 mM (HCO3 (-) ), pH = 6.5] is typically in the range of 1-25 mM and is very dependent upon drug solubility and pKa .

We study experimentally the effect of a mean flow imposed on a buoyant exchange flow of two miscible fluids of equal viscosity in a long tube oriented close to horizontal. We measure the evolution of the front velocity Vf as a function of the imposed velocity V0. At low V0, an exchange-flow dominated regime is found, as expected, and is characterized here by Kelvin–Helmholtz-like instabilities. With increasing V0 we observed that the flow becomes stable. Here also Vf increases linearly with V0 with slope of >1. At large V0 we find Vf∼V0.