Modelling meso-scale diffusion processes in stochastic fluid bio-membranes

The space–time dynamics of rigid inhomogeneities (inclusions) free to move in a randomly fluctuating fluid bio-membrane is derived and numerically simulated as a function of the membrane shape changes. Both vertically placed (embedded) inclusions and horizontally placed (surface) inclusions are considered. The energetics of the membrane, as a two-dimensional (2D) meso-scale continuum sheet, is described by the Canham–Helfrich Hamiltonian, with the membrane height function treated as a stochastic process. The diffusion parameter of this process acts as the link coupling the membrane shape fluctuations to the kinematics of the inclusions. The latter is described via Ito stochastic differential equation. In addition to stochastic forces, the inclusions also experience membrane-induced deterministic forces. Our aim is to simulate the diffusion-driven aggregation of inclusions and show how the external inclusions arrive at the sites of the embedded inclusions. The model has potential use in such emerging fields as designing a targeted drug delivery system.

A hybrid Laplace transform/finite difference boundary element method for diffusion problems

The solution process for diffusion problems usually involves the time development separately from the space solution. A finite difference algorithm in time requires a sequential time development in which all previous values must be determined prior to the current value. The Stehfest Laplace transform algorithm, however, allows time solutions without the knowledge of prior values. It is of interest to be able to develop a time-domain decomposition suitable for implementation in a parallel environment. One such possibility is to use the Laplace transform to develop coarse-grained solutions which act as the initial values for a set of fine-grained solutions. The independence of the Laplace transform solutions means that we do indeed have a time-domain decomposition process. Any suitable time solver can be used for the fine-grained solution. To illustrate the technique we shall use an Euler solver in time together with the dual reciprocity boundary element method for the space solution

Modeling the diffusion of solid copper into liquid solder alloys

During the soldering process, the copper atoms diffuse into liquid solders. The diffusion process determines integrity and the reworking possibility of a solder joint. In order to capture the diffusion scenarios of solid copper into liquid Sn–Pb and Sn–Cu solders, a computer modeling has been performed for 10 s. An analytical model has also been proposed for calculating the diffusion coefficient of copper into liquid solders. It is found that the diffusion coefficient for Sn–Pb solder is 2.74 × 10− 10 m2/s and for Sn–Cu solder is 6.44 × 10−9 m2/s. The modeling results reveal that the diffusion coefficient is one of the major factors that govern the rate at which solid Cu dissolve in the molten solder. The predicted dissolved amounts of copper into solders have been validated with the help of scanning electron microscopic analysis.

Local examination of skin diffusion using FTIR spectroscopic imaging and multivariate target factor analysis

In the context of trans-dermal drug delivery it is very important to have mechanistic insight into the barrier function of the skin's stratum corneum and the diffusion mechanisms of topically applied drugs. Currently spectroscopic imaging techniques are evolving which enable a spatial examination of various types of samples in a dynamic way. ATR-FTIR imaging opens up the possibility to monitor spatial diffusion profiles across the stratum corneum of a skin sample. Multivariate data analyses methods based on factor analysis are able to provide insight into the large amount of spectroscopically complex and highly overlapping signals generated. Multivariate target factor analysis was used for spectral resolution and local diffusion profiles with time through stratum corneum. A model drug, 4-cyanophenol in polyethylene glycol 600 and water was studied. Results indicate that the average diffusion profiles between spatially different locations show similar profiles despite the heterogeneous nature of the biological sample and the challenging experimental set-up.

Simultaneous monitoring of drug and solvent diffusion across a model membrane using ATR-FTIR spectroscopy

Attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy has been used to simultaneously follow the diffusion of model drugs and solvent across polydimethylsiloxane (silicone) membrane. Three model drugs, cyanophenol (CNP), methyl nicotinate (MN) and butyl paraben (BP) were selected to cover a range of lipophilicities. Isostearyl isostearate (ISIS) was chosen as the solvent because its large molecular weight should facilitate observation of whether the drug molecules are able to diffuse through the membrane independently of the solvent. The diffusion of the three drugs and the solvent was successfully described by a Fickian model. The effects of parameters such as the absorption wavelength used to follow diffusion on the calculated diffusion coefficient were investigated. Absorption wavelength which affects the depth of penetration of the infrared radiation into the membrane did not significantly affect the calculated diffusion coefficient over the wavelength range tested. Each of the model drugs was observed to diffuse independently of the solvent across the membrane. The diffusion of a CNP-ISIS hydrogen bonded complex across the membrane was also monitored. The relative diffusion rates of the solute and solvent across the membrane can largely be accounted for by the molecular size of the permeant.

ATR-FTIR spectroscopy and spectroscopic imaging of solvent and permeant diffusion across model membranes

The uptake and diffusion of solvents across polymer membranes is important in controlled drug delivery, effects on drug uptake into, for example, infusion bags and containers, as well as transport across protective clothing. Attenuated Total Reflectance Fourier Transform Infrared (ATR-FTIR) spectroscopy has been used to monitor the effects of different solvents on the diffusion of a model compound, 4-cyanophenol (CNP) across silicone membrane and on the equilibrium concentration of CNP obtained in the membrane following diffusion. ATR-FTIR spectroscopic imaging of membrane diffusion was used to gain an understanding of when the boundary conditions applied to Fick's second law, used to model the diffusion of permeants across the silicone membrane do not hold. The imaging experiments indicated that when the solvent was not taken up appreciably into the membrane, the presence of discrete solvent pools between the ATR crystal and the silicone membrane can affect the diffusion profile of the permeant. This effect is more significant if the permeant has a high solubility in the solvent. In contrast, solvents that are taken up into the membrane to a greater extent, or those where the solubility of the permeant in the vehicle is relatively low, were found to show a good fit to the diffusion model. As such these systems allow the ATR-FTIR spectroscopic approach to give mechanistic insight into how the particular solvents enhance permeation. The solubility of CNP in the solvent and the uptake of the solvent into the membrane were found to be important influences on the equilibrium concentration of the permeant obtained in the membrane following diffusion. In general, solvents which were taken up to a significant extent into the membrane and which caused the membrane to swell increased the diffusion coefficient of the permeant in the membrane though other factors such as solvent viscosity may also be important.