Citation: MIRZAEI, M. and DAS, D.B., 2006. Dynamic effects in capillary pressure-saturations relationships for two-phase flow in 3D porous media: implications of micro-heterogeneities. Chemical Engineering Science, 62 (7), pp. -1947Additional Information:• This article was published in the journal Chemical Engineering

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in Wiley Online Library (wileyonlinelibrary.com).Well defined experiments and numerical analyses are conducted to determine the importance of dynamic effect in capillary pressure relationships for two-phase flow in porous media. Dynamic and quasi-static capillary pressure-saturation (P c -S w ) and, qS w /qt-t curves are determined. These are then used to determine the dynamic effects, indicated by a dynamic coefficient () in the porous domains which establishes the speed at which flow equilibrium (qS w /qt ¼ 0) is reached. s is found to be a nonlinear function of saturation which also depends on the medium permeability. Locally determined s seems to increase as the distance of the measurement point from the fluid inlet into the domain increases. However, the functional dependence s-S w follows similar trends at different locations within the domain. We argue that saturation weighted average of local s-S w curves can be defined as an effective s-S w curve for the whole domain which follows an exponential trend too.

In recent years, there has been a surge in the research and development of microneedles (MNs), a transdermal delivery system that combines the technology of transdermal patches and hypodermic needles. The needles are in the hundreds of micron length range and therefore allow relatively little or no pain. For example, biodegradable MNs have been researched in the literature and have several advantages compared with solid or hollow MNs, as they produce non-sharp waste and can be designed to allow rapid or slow release of drugs. However, they also pose a disadvantage as successful insertion into the stratum corneum layer of the skin relies on sufficient mechanical strength of the biodegradable material. This review looks at the various technologies developed in MN research and shows the rapidly growing numbers of research papers and patent publications since the first invention of MNs (using time series statistical analysis). This provides the research and industry communities a valuable synopsis of the trends and progress being made in this field.

can potentially allow the transdermal delivery of many medicaments including large macromolecules that typically cannot diffuse through the skin. This paper addresses the use of microneedles coated with a drug solution film. In particular, we identify how the geometries of various microneedles affect the drug permeability in skin. Effective skin permeability is calculated for a range of microneedle shapes and dimensions in order to identify the most 20 efficient geometry. To calculate effective permeability (P eff ), the effective skin thickness (H eff ) is calculated. These are then plotted for insulin as a model drug to see how various microneedle parameters affect the profiles of both H eff and P eff . It is found that the depth of penetration from the microneedle array is the most important factor in determining P eff , followed by the microneedle spacings. Other parameters such as microneedle diameter and 25 coating depth are less significant.

in Wiley InterScience (www.interscience.wiley.com).Traditional descriptions of multiphase flow in porous media rely on an extension of Darcy's law along with relationships between capillary pressure (P c ), saturation (S), and relative permeability (K r ). New theories have been proposed which suggest that P c relationships should include a dynamic coefficient (s) (Hassanizadeh and Gray, Water Resour Res. 1993;29:3389-3405) to indicate how ''quickly'' or ''slowly'' flow equilibrium is reached. While validity of these theories must be examined, it is also necessary to determine the significance of s and its range of values. In this article, we analyze the significance of s depending on fluid properties. We address the ways in which they cause nonuniqueness of dynamic two-phase flow in porous media and, hence, dynamic effect. Simulations are conducted for quasi-static and dynamic flow of perchloroethylene (PCE) in water saturated domains. The data are then fitted to the dynamic P c relationships to obtain values of s. The effects of flow directions and, viscosity and density ratios are discussed. To consider the lumped effects of various fluid properties, s-S relationships are examined for silicone oils. The results are interpreted by examining the correlation between s and a mobility coefficient, m. We discuss a scaling relationship that shows the dependence of s on fluid and material properties.The viscosity ratio has practically no effect on quasi-static P c -S relationships and only one P c -S curve is plotted.

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Citation: HAN, T. and DAS, D.B., 2015. Potential of combined ultrasound and microneedles for enhanced transdermal drug permeation: a review. European Journal of Pharmaceutics and Biopharmaceutics,89, Additional Information:• NOTICE: this is the author's version of a work that was accepted for publication in European Journal of Pharmaceutics and Biopharmaceutics. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive ver- have been developed to overcome the resistance of the stratum corneum to molecular 10 diffusion. In particular, researchers have started to consider the possibility of combining the 11 TDD technologies in order to have further increase in drug permeability. Microneedles (MNs) 12 and ultrasound are both promising technologies. They achieve enhancement in drug 13 permeation via different mechanisms and therefore give a good potential for combining with 14 each other. This review will focus on discussing the potential of this combinational technique 15 along with other important issues, e.g., the mechanisms of ultrasound and MNs as it is these 16 mechanisms which are coupled via the two systems (i.e. MNs and ultrasound). We discuss 17 the possible ways to achieve this combination as well as how this combination would 18 increase the permeability. Some of the undeveloped (weaker) research areas of MNs and 19 sonophoresis are also discussed in order to understand the true potential of combining the two 20 technologies when they are developed further in the future. We propose several hypothetical 21 combinations based on the possible mechanisms involved in MNs and ultrasound. 22Furthermore, we carry out a cluster analysis by which we determine the significance of this 23Page 2 of 54 combinational method in comparison with some other selected combinational methods for 24 TDD (e.g., MNs and iontophoresis). Using a time series analysis tool (ARIMA model), the 25 current trend and the future development of combined MNs and ultrasound are also analysed. 26Overall, the review in this paper indicates that combining MNs and ultrasound is a promising 27 TDD method for the future. 28