The long term response of a plume associated with freshwater penetration into ambient, ocean water under upwelling favorable winds is studied using the Regional Ocean Modeling System (ROMS) in an idealized domain. Three different cases were examined, including a shore perpendicular source and shore parallel source with steady winds, and a shore perpendicular source with oscillating alongshore winds. Freshwater flux is used to define plume penetration. Alongshore penetration of buoyant currents is proportional to freshwater input and inversely proportional to upwelling wind stress strength. Strong wind more quickly prevents fresh water’s penetration. Under upwelling favorable winds, the plume is advected offshore by Ekman transport as well as upcoast by the mean flow. This causes the bulge to detach from the coast and move to upcoast and offshore with a 45 degree angle. The path of the bulge is roughly linear, and is independent of wind strength. The bulge speed has a linear relationship with the wind stress strength, and it matches the expected speed based on Ekman theory. Sinusoidal wind leads to sequential upwelling and downwelling events. The plume has an asymmetric response to upwelling and downwelling and fresh water flux is changed immediately by wind. During downwelling, the downcoast fresh water transport is greatest, while it is reduced during upwelling. Background mean flow in the downcoast direction substantially increases alongshore freshwater transport.

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The availability of a drug from a topical preparation is dependent on many factors, one of the most important being the composition of the vehicle. Glycerol, propylene glycol and polyethylene glycol 200 are widely used as ingredients in topical formulations. The aim of this study was to examine how these glycols affected some of the fundamental factors involved in percutaneous absorption of ethyl- methyl- and glycol salicylate. To do this, certain drug-vehicle, drug-vehicle-skin and vehicle-skin interactions were investigated. Drug-vehicle interactions were evaluated using solubility - and rheological measurements, equilibrium dialysis, diffusion coefficient - and release rate determinations. In particular, the study showed that it is important to consider the viscosity contribution of a cosolvent to the vehicle and that it is essential not to over solubilise a drug in the vehicle. The evaluation of drug-vehicle-skin interactions involved both in vitro and in vivo determinations. The in vitro study consisted of solubility- and partition coefficient measurements together with determination of diffusion coefficients and penetration rates for the drugs and the glycols using a two compartment cell in which nude mouse skin was the rate controlling barrier. In vivo, the concentrations of the glycols were determined in the individual layers in the skin and in the plasma of nude mice. The flux of the salicylates was largely unaffected by the various solvent concentrations and the different solvents, except when high concentrations of propylene glycol and glycerol were employed. The measurements of glycerol and propylene glycol in the skin and plasma suggested that the amount of the glycols penetrating into the skin from a topical application were unlikely to have any effect on the partition coefficient of a drug between the vehicle and the skin or the diffusivity of the drug in the skin phase. A comparison of the in vivo and in vitro results indicated a good correlation between these studies. In vivo and in vitro histological assessment were employed to evaluate vehicle-skin effects. Applications of glycerol and PEG 200 had no effect on the skin, whereas increasing concentrations of propylene glycol caused progressive disintegration of the stratum corneum. Some `penetration enhancers' showed unacceptable levels of skin damage and/or irritancy. Future studies may correlate these findings with their penetration enhancing properties.

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Transdermal drug delivery system is in the centre of attention in recent years. For efficient dermal drug delivery the drug has to overcome the barrier of the outermost layer of the skin, the stratum corneum. For facilitating dermal drug transport, the barrier properties of the stratum corneum can be varied by applying chemical penetration enhancers. The aim of this work was to characterize various penetration enhancers and investigate their mechanism of action. We combined well established techniques like differential scanning calorimetry (DSC) and infrared spectroscopy (IR) with confocal Raman microscopy (CRM) as an upcoming technique in skin research. CRM offers the possibility of label-free and non- destructive, chemically selective analysis of stratum corneum lipids and proteins. We used isolated human stratum corneum for incubation with the penetration enhancers. As a novel approach, the samples of treated stratum corneum were freeze dried to avoid any discrepancies which might come up with differences in the hydratation state of stratum corneum (SC). Furthermore, the structure of lipids and proteins in the stratum corneum was analyzed. In our study, stratum corneum was treated with dimethyle sulphoxide, propylene glycol, ethylene glycol, ethylene glycol-d4 and oleic acid. We observed that...