Modelling drug flux through microporated skin

A simple mathematical equation has been developed to predict drug flux through microporated skin. The theoretical model is based on an approach applied previously to water evaporation through leaf stomata. Pore density, pore radius and drug molecular weight are key model parameters. The predictions of the model were compared with results derived from a simple, intuitive method using porated area alone to estimate the flux enhancement. It is shown that the new approach predicts significantly higher fluxes than the intuitive analysis, with transport being proportional to the total pore perimeter rather than area as intuitively anticipated. Predicted fluxes were in good general agreement with experimental data on drug delivery from the literature, and were quantitatively closer to the measured values than those derived from the intuitive, area-based approach.Griffith Health, School of Medical ScienceFull Tex

Background free imaging of upconversion nanoparticle distribution in human skin

Widespread applications of nanotechnology materials have raised safety concerns due to their possible penetration through skin and concomitant uptake in the organism. This calls for systematic study of nanoparticle transport kinetics in skin, where high-resolution optical imaging approaches are often preferred. We report on application of emerging luminescence nanomaterial, called upconversion nanoparticles (UCNPs), to optical imaging in skin that results in complete suppression of background due to the excitation light back-scattering and biological tissue autofluorescence. Freshly excised intact and microneedle-treated human skin samples were topically coated with oil formulation of UCNPs and optically imaged. In the first case, 8- and 32-nm UCNPs stayed at the topmost layer of the intact skin, stratum corneum. In the second case, 8-nm nanoparticles were found localized at indentations made by the microneedle spreading in dermis very slowly (estimated diffusion coefficient, D-np = 3-7 x 10(-12) cm(2) . s(-1)). The maximum possible UCNP-imaging contrast was attained by suppressing the background level to that of the electronic noise, which was estimated to be superior in comparison with the existing optical labels. (C) 2012 Society of Photo-Optical Instrumentation Engineers (SPIE)

Aspects of Mathematical Modelling of Pressure Retarded Osmosis

In power generating terms, a pressure retarded osmosis (PRO) energy generating plant, on a river entering a sea or ocean, is equivalent to a hydroelectric dam with a height of about 60 meters. Therefore, PRO can add significantly to existing renewable power generation capacity if economical constrains of the method are resolved. PRO energy generation relies on a semipermeable membrane that is permeable to water and impermeable to salt. Mathematical modelling plays an important part in understanding flows of water and salt near and across semipermeable membranes and helps to optimize PRO energy generation. Therefore, the modelling can help realizing PRO energy generation potential. In this work, a few aspects of mathematical modelling of the PRO process are reviewed and discussed

Diffusion modeling of percutaneous absorption kinetics. 1. Effects of flow rate, receptor sampling rate, and viable epidermal resistance for a constant donor concentration

A diffusion model for the percutaneous absorption of a solute through the skin is developed for the specific case of a constant donor concentration with a finite removal rate from the receptor due to either perfusion rate or sampling. The model has been developed to include a viable epidermal resistance and a donor-stratum corneum interfacial resistance. Numerical inversion of the laplace domain solutions were used for simulations of solute flux and cumulative amount absorbed and to model specific examples of percutaneous absorption. Limits of the Laplace domain solutions were used to define the steady-state flux, lag time, and receptor concentration. Steady-state approximations obtained from the solutions were used to relate the steady-state flux and the effective permeability coefficient to the viable epidermis resistance, a donor-stratum corneum interfacial resistance, receptor removal rate, and partitioning between the receptor and donor phases. The lag time was shown to be dependent on these parameters and on the Volume of the receptor phase. It is concluded that curvilinear cumulative amount and flux-time profiles are dependent on the processes affecting percutaneous absorption, the shapes of the profiles reflecting the processes most determining transport

Mathematical models for topical and transdermal drug products

Mathematical models of epidermal and dermal transport, which includes transport of a solute through vehicle and various layers of the skin, metabolism in the skin and its subsequent distribution and clearance into systemic circulation from underlying tissues, play an essential role in development of topical and transdermal drug products and are reviewed in this chapter

Modeling the human skin barrier - towards a better understanding of dermal absorption

Many drugs are presently delivered through the skin from products developed for topical and transdermal applications. Underpinning these technologies are the interactions between the drug, product and skin that define drug penetration, distribution, and elimination in and through the skin. Most work has been focused on modeling transport of drugs through the stratum corneum, the outermost skin layer widely recognized as presenting the rate-determining step for the penetration of most compounds. However, a growing body of literature is dedicated to considering the influence of the rest of the skin on drug penetration and distribution. In this article we review how our understanding of skin physiology and the experimentally observed mechanisms of transdermal drug transport inform the current models of drug penetration and distribution in the skin. Our focus is on models that have been developed to describe particular phenomena observed at particular sites of the skin, reflecting the most recent directions of investigation

Mathematical and pharmacokinetic modelling of epidermal and dermal transport processes

Topical delivery to the various regions of the skin and underlying tissues, transdermal drug delivery and dermal exposure to environmental chemicals are important areas of research. Mathematical models of epidermal and dermal transport, involving penetration of a solute through various layers of the skin, metabolism in the skin and its subsequent distribution and clearance into systemic circulation from underlying tissues, play an essential role in this research area and are reviewed in this work

Osmotic power with Pressure Retarded Osmosis:Theory, performance and trends - A review

A great quantity of renewable energy can be potentially generated when waters of different salinities are mixed together. The harnessing of this energy for conversion into power can be accomplished by means of the Pressure Retarded Osmosis (PRO). This technique uses a semipermeable membrane to separate a less concentrated solution, or solvent, (for example, fresh water) from a more concentrated and pressurized solution (for example sea water), allowing the solvent to pass to the concentrated solution side. The additional volume increases the pressure on this side, which can be depressurized by a hydroturbine to produce power - thus the term 'osmotic power'. This paper reviews technical, economical, environmental and other aspects of osmotic power. The latest available research findings are compiled with the objective of demonstrating the rapid advancement in PRO in the last few years - particularly concerning membrane development - and encouraging continued research in this field. Also, the hurdles involved in the effectuation of PRO plants and the research gaps that need to be filled are analyzed in this article. Additionally, osmotic power production using configurations other than the traditional pairing of river water and sea water are discussed. It is hoped that this review will promote further research and development in this new and promising source of renewable energy.Griffith Sciences, Griffith School of EngineeringFull Tex

Modelling dermal drug distribution after topical application in human

Purpose: To model and interpret drug distribution in the dermis and underlying tissues after topical application which is relevant to the treatment of local conditions. Methods: We created a new physiological pharmacokinetic model to describe the effect of blood flow, blood protein binding and dermal binding on the rate and depth of penetration of topical drugs into the underlying skin. We used this model to interpret literature in vivo human biopsy data on dermal drug concentration at various depths in the dermis after topical application of six substances. This interpretation was facilitated by our in vitro human dermal penetration studies in which dermal diffusion coefficient and binding were estimated. Results: The model shows that dermal diffusion alone cannot explain the in vivo data, and blood and/or lymphatic transport to deep tissues must be present for almost all of the drugs tested. Conclusion: Topical drug delivery systems for deeper tissue delivery should recognise that blood/lymphatic transport may dominate over dermal diffusion for certain compounds.

Mathematical models in percutaneous absorption

A number of mathematical models have been used to describe percutaneous absorption kinetics. In general, most of these models have used either diffusion-based or compartmental equations. The object of any mathematical model is to a) be able to represent the processes associated with absorption accurately, b) be able to describe/summarize experimental data with parametric equations or moments, and c) predict kinetics under varying conditions. However, in describing the processes involved, some developed models often suffer from being of too complex a form to be practically useful. In this chapter, we attempt to approach the issue of mathematical modeling in percutaneous absorption from four perspectives. These are to a) describe simple practical models, b) provide an overview of the more complex models, c) summarize some of the more important/useful models used to date, and d) examine sonic practical applications of the models. The range of processes involved in percutaneous absorption and considered in developing the mathematical models in this chapter is shown in Fig. 1. We initially address in vitro skin diffusion models and consider a) constant donor concentration and receptor conditions, b) the corresponding flux, donor, skin, and receptor amount-time profiles for solutions, and c) amount- and flux-time profiles when the donor phase is removed. More complex issues, such as finite-volume donor phase, finite-volume receptor phase, the presence of an efflux. rate constant at the membrane-receptor interphase, and two-layer diffusion, are then considered. We then look at specific models and issues concerned with a) release from topical products, b) use of compartmental models as alternatives to diffusion models, c) concentration-dependent absorption, d) modeling of skin metabolism, e) role of solute-skin-vehicle interactions, f) effects of vehicle loss, a) shunt transport, and h) in vivo diffusion, compartmental, physiological, and deconvolution models. We conclude by examining topics such as a) deep tissue penetration, b) pharmacodynamics, c) iontophoresis, d) sonophoresis, and e) pitfalls in modeling