Mechanisms of chemical and physical transdermal penetration enhancement

The underlying theme of this thesis is one of exploring the processes involved in the enhancement of percutaneous absorption. The development of an attenuated total reflectance Fourier-Transform infrared (ATR-FTIR) spectroscopic method to analyse diffusion of suitable topically applied compounds in membrane is described. Diffusion coefficients (D/h2) and membrane solubility (AO) for topically applied compounds were determined using a solution to Fick's second law of diffusion. This method was employed to determine the diffusional characteristics of a model permeant, 4-cyanophenol (CP), across silicone membrane as a function of formulation applied and permeant physicochemical properties. The formulations applied were able to either affect CP diffusivity and/or its membrane solubility in the membrane; such parameters partially correlated with permeant physicochemical properties in each formulation. The interplay during the diffusion process between drug, enhancer and vehicle in stratum corneum (SC) was examined. When enhancers were added to the applied formulations, CP diffusivity and solubility were significantly enhanced when compared to the neat propylene glycol (PG) application. Enhancers did not affect PG diffusivity in SC but enhancers did affect PG solubility in SC. PG diffusion closely resembled that of CP, implying that the respective transport processes were inter-related. Additionally, a synergistic effect, which increases CP diffusivity and membrane solubility in SC, was found to occur between PG and water. Using 12-azidooleic acid (AOA) as an IR active probe for oleic acid, the simultaneous penetration of CP, AOA and PG into human stratum corneum was determined. It was found that the diffusion profiles for all three permeants were similar. This indicated that the diffusion of each species through SC was closely related and most likely occurred via the same route or SC microenvironment.

Influence of impact angles on penetration rates of CRAs exposed to a high velocity multiphase flow

A combined flow loop - jet impingement pilot plant has been used to determine mass loss rates in a mixed gas - saltwater - sand multiphase flow at impact velocities up to 70 m/s. Artificial brine with a salt content of 27 g/1 was used as liquid phase. Sand content, with grain size below 150 µ, was 2.7 g/l brine. CO at a pressure of 15 bar was used as gas phase. The impact angle between jet stream (nozzle) and sample surface was varied between 30 and 90°. Rectangular stainless steel disc samples with a size of 20 × 15 × 5 mm were used. They were mechanically ground and polished prior to testing. Damaged surfaces of specimens exposed to the high velocity multiphase flow were investigated by stereo microscopy, scanning electron microscopy (SEM) and an optical device for 3D surface measurements. Furthermore, samples were investigated by applying atomic force microscopy (AFM), magnetic force microscopy (MFM) and nanoindentation. Influence of impact velocity and impact angle on penetration rates (mass loss rates) of two CRAs (UNS S30400 and N08028) are presented. Moreover effects of chemical composition and mechanical properties are critically discussed. © 2008 by NACE International.

Studies of skin antisepsis and enhanced penetration of chlorhexidine

Current evidence-based guidelines recommend that 2% (w/v) chlorhexidine digluconate (CHG), preferentially in 70% (v/v) isopropyl alcohol (IIPA), is used for skin antisepsis prior to incision of the skin. In this current study, the antimicrobial efficacy of CHG, six essential oils [tea tree oil (TTO), thymol, eucalyptus oil (EO), juniper oil, lavender oil and citronella] and novel benzylidenecarboxamidrazone and thiosemicarbazone compounds were determined against a panel of microorganisms commonly associated with skin infection (Staphylococcus epidermidis, S. aureus, meticillin-resistant S. aureus, Propionibacterium acnes, Acinetobacter spp., Pseudomonas aeruginosa and Candida albicans) The results demonstrated synergistic activity of CHG in combination with EO against biofilm cultures of S. epidermidis, with significantly reduced concentrations of CHG and EO required to inhibit biofilm growth compared to CHG or EO alone. Skin permeation of CHG was subsequently investigated using an in vitro human skin model (Franz cell) and the penetration profile was determined by serial sectioning of the full thickness human skin. Two percent (w/v) CHG in aqueous solution and in 70% (v/v) IPA demonstrated poor skin permeation; however, the skin permeation was significantly enhanced in combination with 5% - 50% (v/v) EO. Detectable levels of CHG did not permeate through full thickness skin in 24 h. Skin permeation of 2% (w/v) CHG in 70% (v/v) IPA in the presence of 10% (v/v) EO was subsequently studied. The results demonstrated a significantly enhanced skin penetration of CHG after a 2 min application, with CHG detected at significant levels to a depth of 600 m with CHG in combination with EO and IPA compared to 100 m with IPA alone. Combination antisepsis comprising CHG and EO may be beneficial for skin antisepsis prior to invasive procedures to reduce the number of microorganisms on and within the skin due to enhanced skin penetration of CHG and improved efficacy against S. epidermidis in a biofilm mode of growth.

Pluronic F127-modified liposome-containing tacrolimus-cyclodextrin inclusion complexes:improved solubility, cellular uptake and intestinal penetration

Objective The aim of this study was to investigate Pluronic F127-modified liposome-containing cyclodextrin (CD) inclusion complex (FLIC) for improving the solubility, cellular uptake and intestinal penetration of tacrolimus (FK 506) in the gastrointestinal (GI) tract. Methods Molecular modelling was performed to screen the optimal CD for the solubilization of FK 506. FLIC was prepared by thin-lipid film hydration with the inclusion complex solutions followed by membrane extrusion. Dilution tests were conducted in simulated gastric fluids and phosphate-buffered solution of sodium taurocholate to investigate the solubility improvement of FK506. The cellular uptake of nanocarriers was studied in Caco-2 cells, and intestinal mucous membrane penetration in the GI tract was evaluated in Sprague-Dawley rats. Key findings The results showed that β-CD had the strongest binding energy with the guest molecule among the CDs. The prepared FLIC has an average diameter of 180.8 ± 8.1 nm with a spherical shape. The solubility and cellular uptake of FK 506 was greatly improved by the incorporation of CD complexes in the Pluronic F127-modified liposomes. Intestinal mucous membrane penetration was also significantly improved by the preparation of FLIC. Conclusion With improved drug solubility and intestinal mucous membrane penetration, FLIC shows a promising oral delivery system for FK 506. © 2013 Royal Pharmaceutical Society.

Benthic organic carbon flux and oxygen penetration depth in the Southern Ocean

For the investigation of organic carbon fluxes reaching the seafloor, oxygen microprofiles were measured at 145 sites in different sub-regions of the Southern Ocean. At eleven sites, an in situ oxygen microprofiler was deployed for the measurement of oxygen profiles and the calculation of organic carbon fluxes. At four sites, both in situ and ex situ data were determined for high latitudes. Based on this dataset as well as on previous published data, a relationship was established for the estimation of fluxes derived by ex situ measured O2 profiles. The fluxes of labile organic matter range from 0.5 to 37.1 mgC m**2/day. The high values determined by in situ measurements were observed in the Polar Front region (water depth of more than 4290 m) and are comparable to organic matter fluxes observed for high-productivity, upwelling areas like off West Africa. The oxygen penetration depth, which reflects the long-term organic matter flux to the sediment, was correlated with assemblages of key diatom species. In the Scotia Sea (~3000 m water depth), oxygen penetration depths of less than 15 cm were observed, indicating high benthic organic carbon fluxes. In contrast, the oxic zone extends down to several decimeters in abyssal sediments of the Weddell Sea and the southeastern South Atlantic. The regional pattern of organic carbon fluxes derived from micro-sensor data suggest that episodic and seasonal sedimentation pulses are important for the carbon supply to the seafloor of the deep Southern Ocean.

(Table 1) Basement penetration, recovery, and lithology of crustal DSDP holes in the North Atlantic Ocean

Oceanic crustal drilling by R. V. Glomar Challenger at 15 sites in the North Atlantic has led to a complex picture of the upper half kilometer of the crust. Elements of the picture include the absence of the source for linear magnetic anomalies, marked episodicity of volcanic activity, ubiquitous low temperature alteration and evidence for large scale tectonic disturbance. Comparison sections in the Pacific and much deeper crustal drilling are needed to attack problems arising from the North Atlantic results.

Resistance of alkali activated slag concretes to chloride environments based on chloride penetration measurements

Comparing the chloride ingress between tradition concretes and AASCs is worthwhile to prove the possibility of increasing concrete lifetime in proximity to sea and deciding while such concretes are practical for use. Findings show that compared to the PC concretes, the AAS concretes have lower rate of chloride ingress.

Resistance of alkali activated slag concretes to chloride environments based on chloride penetration measurements

ABSTRACT

One of the binder systems with low environmental footprint is alkali activated slag concretes (AASC), made by adding alkalis such as sodium hydroxide and sodium silicate to industrial by-products such as ground granulated blast furnace slag (GGBS). Whilst they have the similar behaviour as that of traditional cement systems in terms of strength and structural behaviour, AASC do exhibit superior performance in terms of abrasion and acid resistance and fire protection.
In this article, the authors focus their attention on chloride ingress into different grades of AASC. The mix variables in AASC included water-to-binder, binder to aggregate ratio, percentage of alkali and the SiO2/Na2O ratio (silica modulus, Ms). The first challenge is to get mixes for different range of workability (with slump values from 40mm to 240mm) and reasonable early age and long term compressive strength according to each one. Then the chloride diffusion and migration in those mixes were measured and compared with same normal concretes in the existed literature based on chloride penetration depth. Comparing the chloride ingress between tradition concretes and AASCs is worthwhile to prove the possibility of increasing concrete lifetime in proximity to sea and deciding while such concretes are practical for use. Findings show that compared to the PC concretes, the AAS concretes have lower rate of chloride ingress.

Multiscale Analysis for Field-Effect Penetration through Two-Dimensional Materials

Gate-tunable two-dimensional (2D) materials-based quantum capacitors (QCs) and van der Waals heterostructures involve tuning transport or optoelectronic characteristics by the field effect. Recent studies have attributed the observed gate-tunable characteristics to the change of the Fermi level in the first 2D layer adjacent to the dielectrics, whereas the penetration of the field effect through the one-molecule-thick material is often ignored or oversimplified. Here, we present a multiscale theoretical approach that combines first-principles electronic structure calculations and the Poisson–Boltzmann equation methods to model penetration of the field effect through graphene in a metal–oxide–graphene–semiconductor (MOGS) QC, including quantifying the degree of “transparency” for graphene two-dimensional electron gas (2DEG) to an electric displacement field. We find that the space charge density in the semiconductor layer can be modulated by gating in a nonlinear manner, forming an accumulation or inversion layer at the semiconductor/graphene interface. The degree of transparency is determined by the combined effect of graphene quantum capacitance and the semiconductor capacitance, which allows us to predict the ranking for a variety of monolayer 2D materials according to their transparency to an electric displacement field as follows: graphene > silicene > germanene > WS2 > WTe2 > WSe2 > MoS2 > phosphorene > MoSe2 > MoTe2, when the majority carrier is electron. Our findings reveal a general picture of operation modes and design rules for the 2D-materials-based QCs.

Cone penetration testing to assess slope stability in the 1979 Nice landslide area (Ligurian Margin, SE France)

In the landslide-prone area near the Nice international airport, southeastern France, an interdisciplinary approach is applied to develop realistic lithological/geometrical profiles and geotechnical/strength sub-seafloor models. Such models are indispensable for slope stability assessments using limit equilibrium or finite element methods. Regression analyses, based on the undrained shear strength (su) of intact gassy sediments are used to generate a sub-seafloor strength model based on 37 short dynamic and eight long static piezocone penetration tests, and laboratory experiments on one Calypso piston and 10 gravity cores. Significant strength variations were detected when comparing measurements from the shelf and the shelf break, with a significant drop in su to 5.5 kPa being interpreted as a weak zone at a depth between 6.5 and 8.5 m below seafloor (mbsf). Here, a 10% reduction of the in situ total unit weight compared to the surrounding sediments is found to coincide with coarse-grained layers that turn into a weak zone and detachment plane for former and present-day gravitational, retrogressive slide events, as seen in 2D chirp profiles. The combination of high-resolution chirp profiles and comprehensive geotechnical information allows us to compute enhanced 2D finite element slope stability analysis with undrained sediment response compared to previous 2D numerical and 3D limit equilibrium assessments. Those models suggest that significant portions (detachment planes at 20 m or even 55 mbsf) of the Quaternary delta and slope apron deposits may be mobilized. Given that factors of safety are equal or less than 1 when further considering the effect of free gas, a high risk for a landslide event of considerable size off Nice international airport is identified

Effect of different methods of soil preparation on soil moisture loss, weed growth and soil resistance to penetration.

The effect of different methods of soil preparation on soil moisture loss, weed growth and soil resistance to penetration has been quantified for the Latosols of Bebedouro experiment station of CPATSA-EMBRAPA, Petrolina,PE, Brazil. The methods studied are manual preparation, preparation by animal drawn wheeled tool carrier and tractorized implements. The drying characteristics of three fields with different soil physical properties were studied prior to conducting the experiment. The different methods of soil preparation caused the soil moisture loss differently. The plot prepared by animal drawn tool carrier retained more moisture for longer time even at deeper layers. The soil resistance to penetration on the surface increased with time with little variation at deeper layers.

The effect of alternate supply of shielding gases in austenite stainless steel GTA welding

Welding system has now been concentrated on the development of new process to achieve cost savings, higher productivity and better quality in manufacturing industry. Discrete alternate supply of shielding gas is a new technology that alternately supplies the different kinds of shielding gases in weld zone. As the newdevelopedmethods compared to the previous generalwelding with a mixing supply of shielding gas, it cannot only increase thewelding quality, but also reduce the energy by 20% and the emission rate of fume. As a result, under thesamewelding conditions,comparedwith thewelding by supplying pure argon, argon + 67% helium mixture by conventional method and thewelding by supplying alternately pure argon and pure helium by alternate method showed the increased welding speed. Also, the alternate method showed the same welding speed with argon + 67% helium mixture without largely deteriorating of weld penetration. The alternate method with argon and helium compared with the conventional methods of pure argon and argon + 67% helium mixture produced the lowest degree of welding distortion.