Steady-state Diffusion Coefficient Research Articles

Revealing the functional relationship between manganese dissolution potentials and lithium concentrations with diffusion coefficient for lithium intercalation in λ-MnO2 electrode

Electrochemical redox lithium extraction (ELE) with LiMn2O4/λ-MnO2 redox couple, stands out as the most prospective technology for efficient and selective lithium extraction from the salt lake brines owing to the high lithium intercalation capacity, selectivity, and recovery rate. However, the decreasing Li+ concentration induced electrode polarization, especially, at low concentrations, and inappropriately applied potentials can significantly accelerate manganese dissolution (MD). While no correlational research has established the relationship between the manganese dissolution potential (EMD) and Li+ concentration gradient. Herein, the inversely proportional relationship between EMD and the lithium concentration is first revealed through steady-state diffusion coefficients. This research sheds light on the MD mechanism at different lithium concentration gradients and lays the foundation for the industrial application of electrochemical lithium extraction with LiMn2O4/λ-MnO2 redox couple from salt lake brines.

Convection-diffusion-electromigration coupled numerical simulation of water and chloride in cement-based materials

The transport of chloride in cement-based materials is influenced by various factors, and the chloride diffusion coefficient in numerical models should be the steady-state value under specific conditions, which is difficult to obtain through traditional experiments. In this article, based on an improved non-contact resistivity instrument, the steady-state chloride diffusion coefficient and porosity of cement-based materials are characterized. Considering the acceleration effect of moisture convection and electric field on chloride transport, a numerical model for moisture and chloride transport coupling diffusion, convection, and electromigration is established. Based on the measured steady-state chloride diffusion coefficient and porosity values, the influence of interface transition zone (ITZ), electric field type, chloride binding effect, initial conditions, and boundary conditions on moisture and chloride transport is numerically analyzed. It is found that the increase of ITZ thickness, electric field strength, boundary concentration, and initial concentration can accelerate chloride transport. The chloride concentration distribution curve exhibits a “shoulder peak” caused by chloride binding effect, and its peak height and width are positively correlated with the chloride binding coefficient. In conclusion, this study aims to better understand the ion transport behavior inside cement-based materials under coupling of convection, diffusion, and electromigration, and identify the key factors influencing this behavior, which provide a feasible scheme for durable design of concrete construction in environments rich in erosive media.

Resistivity and chloride diffusion coefficient of cement-based materials characterized by non-contact electrical resistivity method and resistivity model

The present study involves the application of the non-contact electrical resistivity measurement (NC-ERM) as a non-destructive method to continuously and in-situ measure the resistivity changes of cement-based materials. The NC-ERM was enhanced and utilized to evaluate the resistivity of the materials, and the steady-state chloride diffusion coefficients of various types of cement-based materials were experimentally determined. The results revealed that the highest resistivity was observed in mortar with a sand-to-cement ratio of 1.0 and concrete with an aggregate-to-cement ratio of 0.6, and the steady-state chloride diffusion coefficient increased with the concentration of the pore solution. Furthermore, a novel multi-level series-parallel model was developed to predict the resistivity and steady-state chloride diffusion coefficient of cement-based materials, with calculated values differing by 5% or less. The calculated chloride diffusion coefficient closely matched the value obtained from NC-ERM, indicating the satisfactory accuracy of the non-destructive experiment and theoretical calculation model.

The Effect of Herbal Penetration Enhancers on the Skin Permeability of Mefenamic Acid Through Rat Skin.

Mefenamic acid (MA) is a strong non-steroidal anti-inflammatory drug, but because of its limited oral bioavailability and the side effects that come with taking it systemically, it is better to apply it topically. The major goal of this study was to see how certain permeation enhancers affected MA is in vitro skin permeability. In manufactured Franz diffusion cells, MA permeability tests using rat skin pretreatment with several permeation enhancers such as corn oil, olive oil, clove oil, eucalyptus oil, and menthol were conducted and compared to hydrate rat skin as a control. The steady-state flux (Jss), permeability coefficient (Kp), and diffusion coefficient are among the permeability metrics studied. The permeability enhancement mechanisms of the penetration enhancer were investigated using fourier transform infrared spectroscopy (FTIR) to compare changes in peak position and intensities of asymmetric and symmetric C-H stretching, C=O stretching, C=O stretching (amide I), and C-N stretching of keratin (amide II) absorbance, as well as differential scanning calorimetry (DSC) to compare mean transition temperature and their enthalpies. Clove oil, olive oil, and eucalyptus oil were the most effective enhancers, increasing flux by 7.91, 3.32, and 2.6 times, as well as diffusion coefficient by 3.25, 1.34, and 1.25, respectively, when compared to moist skin. FTIR and DSC data show that permeation enhancers caused lipid fluidization, extraction, disruption of lipid structures in the SC layer of skin, and long-term dehydration of proteins in this area of the skin. According to the findings, the permeation enhancers used improved drug permeability through excised rat skin. The most plausible mechanisms for greater ERflux, ERD, and ERP ratios were lipid fluidization, disruption of the lipid structure, and intracellular keratin irreversible denaturation in the SC by eucalyptus oil, menthol, corn oil, olive oil, and clove oil.

Water transport in calcium silicate hydrate nanoscale pores by molecular dynamics: Unsaturated steady-state diffusion and suction

Water transfer in calcium silicate hydrate (CSH) nanoscale pores is an important factor affecting the durability of cement-based materials. Using molecular dynamics, the transport behaviour of nanoscale water in unsaturated CSH gel pores can be simulated to explore the transport law and mechanism of unsaturated water in the gel pores. In this paper, two kinds of transport models were established: an unsaturated steady-state diffusion model and a suction model. The effects of pore size and saturation level on the steady-state density distribution, dipole orientation, dipole moment and diffusion coefficient of water in each region were studied. Then, the influence of temperature, pore diameter, initial saturation level and tortuosity on the water absorption rate in the suction process was analysed, and the CSH molecular formula for the saturation state was calculated. The results showed that the distribution of water in the CSH gel pore was mainly related to the saturation level and wall position, and the percolation effect was triggered when the saturation of the gel pore reached 53 %. Water molecules located in the interlayer zone, adsorption zone and free zone exhibit the laws of the free zone > adsorption zone > interlayer zone due to the differences in geometric constraints and bonding. With the increase in the saturation level of water in the gel pore, the overall diffusion coefficient of water presents a change law of first rising and then falling. A higher temperature will magnify the effect on the promotion of transport. The pore size of the gel pore is positively correlated with the diffusion capacity of water, while higher initial saturation level and tortuosity will both inhibit the absorption rate of the gel pore. The CSH formula in the saturated stable state is (CaO)1.65SiO2(H2O)2.1. For cement-based materials with a high proportion of large gel pores (above 2 nm), limiting the saturation level in the gel pores below the percolation threshold (preferably below 45 %) as far as possible can effectively inhibit the water transport capacity. The simulation results are in good agreement with the data in the literature.

The Effect of Vegetable and Volatile Oils on the Piroxicam Skin Permeability: A Mechanistic Study

Background: Piroxicam is a non-steroidal anti-inflammatory medication for treating fever, discomfort, and inflammation. In addition, piroxicam inhibits cyclooxygenase and lowers prostaglandin synthesis, resulting in analgesic and anti-inflammatory effects. Objectives: This study used Franz diffusion cells made from rat skin primed with sesame, eucalyptus, olive, menthol, clove, and sunflower oils. Methods: Control was hydrated rat skin. Permeability measurements include steady-state flux (Jss), permeability coefficient (Kp), and diffusion coefficient (D). FT-IR was used to compare changes in peak position, differential scanning calorimeter (DSC), mean transition temperature, and the permeability enhancement methods of the penetration enhancer (Tm). The skin acted as a barrier to piroxicam permeability throughout the whole surface, indicating that drug flux was limited by diffusion into the skin. Results: The steady-state flux (Jss) of all penetration enhancers were not significantly different from control, except for clove and menthol oil (4 hours treated) and olive oil (2 and 4 hours treated). Conclusions: Penetration enhancers improved drug permeability through rat skin. Sesame oil, menthol oil, and sesame oil were found to have higher ERflux, ERD, and ERP ratios than water-hydrated skin due to lipid fluidization, lipid structure disruption, and irreversible keratin denaturation.

Topical Nanoemulgel for the Treatment of Skin Cancer: Proof-of-Technology.

The present study is a mechanistic validation of ‘proof-of-technology’ for the effective topical delivery of chrysin nanoemulgel for localized, efficient treatment of melanoma-affected skin. Background: Currently available treatments for skin cancer are inefficient due to systemic side effects and poor transcutaneous permeation, thereby presenting a formidable challenge for the development of novel nanocarriers. Methods: We opted for a novel approach and formulated a nanocomplex system composed of hydrophobic chrysin dissolved in a lipid mix, which was further nanoemulsified in Pluronic® F-127 gel to enhance physicochemical and biopharmaceutic characteristics. Chrysin, a flavone extracted from passion flowers, exhibits potential anti-cancer activities; however, it has limited applicability due to its poor solubility. Pseudo-ternary phase diagrams were constructed to identify the best self-nanoemulsifying region by varying the compositions of oil, Caproyl® 90 surfactant, Tween® 80, and co-solvent Transcutol® HP. Chrysin-loaded nanoemulsifying compositions were characterized for various physicochemical properties. Results: This thermodynamically stable, self-emulsifying drug delivery system showed a mean droplet size of 156.9 nm, polydispersity index of 0.26, and viscosity of 9100 cps after dispersion in gel. Mechanical characterization using Texture Analyzer exhibited that the gel had a hardness of 487 g and adhesiveness of 500 g. Ex vivo permeation through rat abdominal skin revealed significant improvement in percutaneous absorption measured as flux, the apparent permeability coefficient, the steady-state diffusion coefficient, and drug deposition. In vitro cytotoxicity on A375 and SK-MEL-2 cell lines showed a significantly improved therapeutic effect, thus ensuring reduction in dose. The safety of the product was established through biocompatibility testing on the L929 cell line. Conclusion: Aqueous, gel-based, topical, nanoemulsified chrysin is a promising technology approach for effective localized transcutaneous delivery that will help reduce the frequency and overall dose usage and ultimately improve the therapeutic index.

Microstructure and Durability Performance of Mortars with Volcanic Powder from Calbuco Volcano (Chile) after 4 Hardening Years.

One of the most popular ways to lessen the impact of the cement industry on the environment consists of substituting clinker by additions. The service life required for real construction elements is generally long, so it would be interesting to obtain information about the effects of new additions after a hardening period of several years. Analyzed here are the effects of the incorporation of volcanic ashes, coming from Calbuco volcano’s last eruption (Chile), as clinker replacement, in the durability and pore structure of mortars, after approximately 4 hardening years (1500 days), in comparison with reference specimens without additions. The substitution percentages of clinker by volcanic powder studied were 10% and 20%. The microstructure was characterized with mercury intrusion porosimetry and impedance spectroscopy. In order to evaluate the pozzolanic activity of the volcanic powder after 1500 days, differential thermal analyses were performed. Water absorption after immersion, steady-state diffusion coefficient and length change were also studied. In accordance with the results obtained, the 10% and 20% substitution of clinker by volcanic powder from the Calbuco volcano showed beneficial effects in the mortars after 4 years, especially regarding the microstructure and chloride diffusion, without noticeable influence in their water absorption.

Effects after 1500 Hardening Days on the Microstructure and Durability-Related Parameters of Mortars Produced by the Incorporation of Waste Glass Powder as a Clinker Replacement

One of the ways of lessening the CO2 emissions of cement industry consists of replacing clinkers with supplementary cementitious materials. The required service life of real construction elements is long, so it is useful to characterize the performance of these materials in the very long term. Here, the influence of incorporating waste glass powder as a supplementary cementitious material, regarding the microstructure and durability of mortars after 1500 hardening days (approximately 4 years), compared with reference mortars without additions, was studied. The percentages of clinker replacement by glass powder were 10% and 20%. The microstructure was studied using impedance spectroscopy and mercury intrusion porosimetry. Differential thermal and X-ray diffraction analyses were performed for assessing the pozzolanic activity of glass powder at the end of the time period studied. Water absorption after immersion, the steady-state diffusion coefficient, and length change were also determined. In view of the results obtained, the microstructure of mortars that incorporated waste glass powder was more refined compared with the reference specimens. The global solid fraction and pores volume were very similar for all of the studied series. The addition of waste glass powder reduced the chloride diffusion coefficient of the mortars, without worsening their behaviour regarding water absorption after immersion.

Gas Steady-state Diffusion in Fractal Porous Media

Gas diffusion in fractal pores does not follow the classic Fick’s and Knudsen’s laws, so more research on gas diffusion in fractal porous media is needed. Fractal pore models are generated using the random walk method. The gas diffusion governing equations for the fractal pores are derived from the classic kineti theory of gases. The gas diffusion model is used to study the gas diffusion in fractal porous meida and to determine steady-state diffusion coefficient formulas. The results show that the diffusion coefficient is proportional to the mean proe diameter, porosity, and the exponetial function of the fractal dimension in the Knudsen diffusion regime. The diffusion coefficient is not only related to the three pore parameters but is also related to the molecular mean free path in the configurational diffusion regime.

The relationship between steady-state chloride diffusion and migration coefficients in cementitious materials

The chloride diffusion coefficient is directly related to the property of concrete to resist the ingress of chloride ions and it is a decisive factor for the durability of reinforced concrete subjected to the chloride environment. The conventional chloride diffusion test requires considerable time to attain a steady-state chloride flow across the specimen. Therefore, the rapid chloride migration test is frequently employed with an applied electrical field to accelerate the chloride transport. However, the chloride diffusion coefficient estimated based on the rapid chloride migration test is different compared to the actual chloride diffusion coefficient. In this study, a theoretical model of the relationship between the steady-state chloride diffusion coefficient and chloride migration coefficient has been obtained for cementitious materials. Based on the theoretical model, an empirical model of the relationship between steady-state chloride diffusion and migration coefficients is proposed for cementitious materials. Furthermore, the parameters of the empirical model were obtained through the results of chloride diffusion and migration tests on a range of mortar mixtures made with ordinary Portland cement and blended cements with additions of ground granulated blast furnace slag, pulverised fuel ash and silica fume, and the published data from other researchers.

A three-step analytical scheme for estimating the steady-state chloride diffusion coefficient of mature cement paste

The intention of this paper is to estimate the steady-state chloride diffusion coefficient of mature cement paste through laboratory test and theoretical analysis. In the test, the chloride diffusion coefficient of cement paste with water/cement ratios of 0.3, 0.4, 0.5, and 0.6 is measured at curing ages from 28 to 1800 days. The test results show that, for cement paste cured for smaller than 360 days, the chloride diffusion coefficient reduces quickly with the increase of curing age. For cement paste cured for larger than 360 days, however, the chloride diffusion coefficient decreases slowly with increasing the curing age. In view of the multi-phase and multi-scale characteristics of cement paste, a three-step scheme is developed to derive the chloride diffusion coefficient analytically. In the scheme, the chloride diffusion coefficients of the inner and outer hydration products and the solid phase are formulated with a two- and three-phase composite sphere models, respectively. Finally, for the bi-continuous cement paste system composed of a solid phase and capillary pores, the effective medium method is adopted to deduce the chloride diffusion coefficient. Eight sets of experimental data, obtained in this paper and collected from the literature, are used to verify the analytical scheme. It is concluded that the developed three-step analytical scheme can evaluate the chloride diffusion coefficient of mature cement paste with reasonable accuracy.

Diffusion of chemicals into archaeological waterlogged hardwoods obtained from the Thang Long Imperial Citadel site, Vietnam

This study shows a method to easily develop suitable impregnation procedure of chemicals for preserving the archaeological waterlogged wood (WW) using diffusion constant. The steady-state diffusion coefficients of polyethylene glycol 4000 (PEG4000), trehalose, and keratin through eight archaeological waterlogged wood species were obtained from the total amounts of the chemicals diffused through the wood samples. The diffusion coefficients were strongly affected by the anatomical structures of the wood species and degree of wood deterioration. Within the same species of wood, the highest diffusion rates were measured in the longitudinal direction, followed by those in the radial and tangential directions. The longitudinal diffusion coefficients were 1.5- to 8.1-times higher than the radial diffusion coefficients, which were in turn approximately 1.1- to 5.7-times higher than the tangential diffusion coefficients. The diffusion rates were found to be inversely proportional to the molecular weight of the diffusing chemical. The diffusivity of trehalose through the waterlogged woods was found to be higher than those of keratin and PEG4000. This study provides a potential method to easily estimate chemical diffusion coefficients for dip-diffusion treatments.

Diffusion through the ex vivo vitreal body – Bovine, porcine, and ovine models are poor surrogates for the human vitreous

The human vitreous humour is a complex gel structure whose composition and physical properties can vary considerably from person to person and also change with age. To date, the viscoelastic properties of the human vitreous gel has not been thoroughly investigated and despite many years of intensive research, an ideal vitreous substitute remains a challenge. Understanding the physical structure and properties of the vitreous is of fundamental and therapeutic interest, providing a clear insight into diffusion and transport of administered ophthalmic drug molecules into the vitreous. A number of mammalian surrogates, mainly bovine, porcine and ovine vitreous humours have been used in the literature as a means of studying ophthalmic drug transport and diffusion. In this study, the mechanical, physical and rheological properties of ovine, porcine, and bovine surrogates were investigated and compared to human vitreous. In addition, a bespoke Franz cell construct was used to compare the diffusion of a model drug (fluorescein) through vitreous samples. Despite the similarity in rheological properties between bovine, porcine and human vitreous samples, diffusion of fluorescein through the different vitreous samples revealed great differences in values of steady-state flux and diffusion coefficient. In addition, a first-generation vitreous mimic, composed of 4.5 mg/mL hyaluronic acid with complex viscosity of 0.3 ± 0.01 Pa has been evaluated and was demonstrated to be a better mimic of the human vitreous than the mammalian samples investigated.

Short-Term Performance of Sustainable Silica Fume Mortars Exposed to Sulfate Attack

Nowadays, the reuse of wastes is essential in order to reach a more sustainable environment. The cement production results in CO2 emissions which significantly contribute to anthropogenic greenhouse gas emissions. One way to reduce them is by partially replacing clinker by additions, such as silica fumes or other wastes. On the other hand, the pore structure of cementitious materials has a direct influence on their service properties. One of the most popular techniques for characterizing the microstructure of those materials is mercury intrusion porosimetry. In this work, this technique has been used for studying the evolution of the pore network of mortars with different percentages of silica fume (until 10%), which were exposed to aggressive sodium and magnesium sulfate solutions up to 90 days. Between the results of this technique, intrusion-extrusion curves and logarithms of differential intrusion volume versus pore size curves were studied. This characterization of the pore network of mortars has been complemented with the study of their compressive strength and their steady-state ionic diffusion coefficient obtained from samples’ resistivity. Generally, silica fume mortars showed different performance depending on the aggressive condition, although the greatest deleterious effects were observed in the medium with presence of both magnesium and sodium sulfates.

INFLUENCE OF PERMEATION ENHANCERS ON THE IN VITRO SKIN PERMEATION OF KETOROLAC TROMETHAMINE THROUGH EXCISED RAT SKIN: A MECHANISTIC STUDY

Objective: Ketorolac tromethamine (KT) is considered as a member of Non-steroidal anti-inflammatory drugs that used as an analgesic and antipyretic agent. The main aim of this research was to investigate the effect of some herbal and chemical permeation enhancers on the in vitro skin permeability of KT.Method: Ketorolac permeability experiments through rat skin pre-treated with some of permeation enhancers, namely urea, eucalyptus oil, olive oil, and menthol, were performed in fabricated Franz diffusion cells and compared with hydrated rat skin as control. The permeability parameters evaluated include steady-state flux (Jss), permeability coefficient (Kp), and diffusion coefficient (D). The penetration enhancers permeability enhancement mechanisms were investigated by comparing changes in peak position and their intensities of asymmetric (Asy) and symmetric (Sym) C-H stretching, C=O stretching, C=O stretching (Amide I), and C-N stretching of keratin (Amide II) absorbance using fourier transform infrared spectroscopy (FT-IR), as well as by comparing mean transition temperature (Tm) and their enthalpies (ΔH) using differential scanning calorimetery (DSC). KT permeability parameters through rat skin were evaluated with and without chemical enhancers such as eucalyptus oil, olive oil, menthol, and urea.Result: The skin showed barrier for ketorolac permeability through the whole skin and that diffusion into the skin was the rate-limiting step for drug flux. Urea, eucalyptus oil, olive oil, and menthol were the most effective enhancers as they increased flux 0.02, 0.017, 0.016, and 0.012 times and diffusion coefficient 0.079, 0.194, 0.129, and 1.35 folds in comparison with hydrated skin, respectively.Conclusion: FT-IR and DSC results showed lipid fluidization, extraction, disruption of lipid structure, and irreversible denaturation of proteins in the stratum corneum layer of the skin by permeation enhancers.

Influence of Chemical Permeation Enhancers on the in vitro Skin Permeation of Minoxidil through Excised Rat Skin: A Mechanistic Study

Abstract: Minoxidil, a pyrimidine derivative (2, 4-diamino-6-piperidinopyrimidine-3-oxide) is the only topical medical treatment with proven efficacy for the treatment of Androgenetic alopecia that shown low skin penetration and bioavailability. The main aim of this research was to investigate the effect of some permeation enhancers on the in vitro skin permeability of minoxidil . Minoxidil permeability experiments through rat skin pretreated with some of permeation enhancers namely, Urea, Eucalyptus oil and Menthol were performed in fabricated Franz diffusion cells and compared with hydrated rat skin as control. The permeability parameters evaluated include steady-state flux (Jss), permeability coefficient (Kp) and diffusion coefficient (D). The penetration enhancer’s permeability enhancement mechanisms were investigated by comparing of changes in peak position and their intensities of asymmetric (Asy) and symmetric (Sym) C-H stretching, C=O stretching, C=O stretching (Amide I) and C-N stretching of keratin (Amide II ) absorbance using Fourier transform infrared spectroscopy (FTIR), as well as by comparing mean transition temperature (Tm) and their enthalpies (∆H) using differential scanning calorimetery (DSC). Minoxidil permeability parameters through rat skin, were evaluated with and without chemical enhancers such as Eucalyptus oil, menthol and urea. The skin showed barrier for minoxidil permeability through whole skin and that diffusion into the skin was the rate-limiting step for drug flux. Urea , Eucalyptus oil and Menthol were the most effective enhancers as they increased flux 1.86 ,2.16 and 1.75 times and diffusion coefficient 3.25,1.34 and 2.16 folds in comparison with hydrated skin, respectively. FTIR and DSC results showed lipid fluidization , extraction ,disruption of lipid structure and irreversible denaturation of proteins in the SC layer of skin by permeation enhancers.

The Effect of Various Vehicles on the Naproxen Permeability through Rat Skin: A Mechanistic Study by DSC and FT-IR Techniques.

The purpose of the present investigation was to evaluate the effectiveness of different vehicles on drug permeability and microstructure of intercellular or lipids in SC layer of skin. Pre-treated skin of rat using some vehicles including Labarac PG ,Transcutol P, tween 80, span 80 and propylene glycol (PG), were mounted on specialized design franz-diffusion cell was used to assess naproxen permeation and parameters such as permeability coefficients and state flux (Jss) were evaluated. Any differences in peak position and also change in symmetric and asymmetric stretching of C-H bond, lipid ester carbonyl stretching in SC, C=O stretching (Amide I) and C-N stretching of keratin (Amide II) absorbance using Fourier transform infrared spectroscopy (FTIR) were considered to investigate the enhancing mechanism. DSC method was utilized to compare their mean transition temperature (Tm) and enthalpies (ΔH). Steady-state flux (Jss), permeability coefficient (Kp) and diffusion coefficient (D) were significantly (p<0.05) increased by using their span80 showed the biggest enhancement ratio (ERflux) and Transcutol P, Labrafac PG, Tween 80 and Propylene glycol were at the next levels. In comprised to hydrated rat skin the maximum increase in diffusion coefficient was for Tween 80(p<0.05), Lipid fluidization, lipid disruption structure and the irreversible denaturation of proteins in the SC layer of skin by span 80, Tween 80, Labrafac PG, Transcutol P and propylene glycol, were indicated by FT-IR and DSC techniques. It is concluded that naproxen permeation through rat skin may be facilitated by utilizing the vehicle systems. Lipid fluidization and lipid extraction are among suggested mechanisms.

The Effect of Various Vehicles on the Naproxen Permeability through Rat Skin: A Mechanistic Study by DSC and FT-IR Techniques.

The purpose of the present investigation was to evaluate the effectiveness of different vehicles on drug permeability and microstructure of intercellular or lipids in SC layer of skin. Pre-treated skin of rat using some vehicles including Labarac PG ,Transcutol P, tween 80, span 80 and propylene glycol (PG), were mounted on specialized design franz-diffusion cell was used to assess naproxen permeation and parameters such as permeability coefficients and state flux (Jss) were evaluated. Any differences in peak position and also change in symmetric and asymmetric stretching of C-H bond, lipid ester carbonyl stretching in SC, C=O stretching (Amide I) and C-N stretching of keratin (Amide II) absorbance using Fourier transform infrared spectroscopy (FTIR) were considered to investigate the enhancing mechanism. DSC method was utilized to compare their mean transition temperature (Tm) and enthalpies (ΔH). Steady-state flux (Jss), permeability coefficient (Kp) and diffusion coefficient (D) were significantly (p<0.05) increased by using their span80 showed the biggest enhancement ratio (ERflux) and Transcutol P, Labrafac PG, Tween 80 and Propylene glycol were at the next levels. In comprised to hydrated rat skin the maximum increase in diffusion coefficient was for Tween 80(p<0.05), Lipid fluidization, lipid disruption structure and the irreversible denaturation of proteins in the SC layer of skin by span 80, Tween 80, Labrafac PG, Transcutol P and propylene glycol, were indicated by FT-IR and DSC techniques. It is concluded that naproxen permeation through rat skin may be facilitated by utilizing the vehicle systems. Lipid fluidization and lipid extraction are among suggested mechanisms.

Transcutaneous delivery of leflunomide nanoemulgel: Mechanistic investigation into physicomechanical characteristics, in vitro anti-psoriatic and anti-melanoma activity

The present study is a mechanistic validation of ‘proof of concept’ of effective topical delivery of leflunomide (LFD) nanoemulgel for localized efficient treatment of psoriatic lesions as well as melanoma affected skin regions. Hyperproliferation of keratinocytes in psoriasis and symbiotic relationship between keratinocytes and melanocytes, justifies the need of dual acting treatment. LFD is recently introduced significantly effective disease modifying anti-rheumatic drug and has been considered valuable for the treatment of psoriatic arthritis as well as melanoma. Current available treatments for psoriasis and melanoma are inefficient due to systemic side effects, poor transcutaneous permeation and thus present a challenge for development of novel colloidal carriers. We newly reformulated LFD as a nanoemulgel based on self nanoemulsifying technique using Capryol 90, Cremophor EL, Transcutol HP as nanoemulsifying components and Pluronic F127 as a gelling agent. This thermodynamically stable nanoemuslsifying preconcentrate after gelation showed mean globule size, 123.7nm and viscosity 9620±93cp. Complete mechanical characterization was carried out using Texture Analyzer and hardness, adhesiveness and springiness index were found to be 523gms, 431gms and 1.02, respectively. Ex vivo permeation through rat abdominal skin revealed significant improvement in flux, apparent permeability coefficient, steady state diffusion coefficient and drug deposition in skin due to nanoemulsification of LFD. The in vitro cytoxicity of LFD nanoemulgel in human HaCaT, melanoma A375 and SK-MEL-2 cell lines showed significantly enhanced therapeutic response. In gist, LFD nanoemulgel for trancutaneous delivery will reduce the overall dose and drug consumption, by effectively localizing at the applied target site and will ultimately minimize systemic side effects.