Transdermal absorption of L-dopa from a new system composed of two separate layers of L-dopa and hydrogel in rats

To maintain the stability of L-dopa in hydrogel, a new system composed of two separate layers of L-dopa and hydrogel was developed. L-Dopa sheets were made by immersing L-dopa solution into wiper sheets and by lyophilizing them. Examination for stability of L-dopa in the L-dopa sheet revealed that its stability was maintained for at least 12 weeks, providing the sheet was kept at room temperature in a dark box. In a cutaneous absorption study of L-dopa in rats, an L-dopa sheet was attached to the shaved abdominal skin. A hydrogel composed of cutaneous absorption enhancers, water and ethanol, was spread on vinyl tape (hydrogel sheet), and this sheet was placed over the L-dopa sheet. L-Dopa that was administered transdermally effectively penetrated through the skin: The plasma level of L-dopa peaked at 30 min and remained high between 60 and 180 min after the cutaneous application. Our system, composed of two separated layers of L-dopa and hydrogel, enabled the stability of L-dopa to be maintained without losing transdermal absorption of L-dopa.     

Limonene and Related Compounds as Potential Skin Penetration Promoters

A transdermal therapeutic system can be developed by promoting the skin permeability of drugs with some materials. In this study, the promoting effect of terpenes present in essential oils on the percutaneous absorption of indomethacin from alcoholic hydrogels was investigated in rats in vivo. The enhancing activity of terpenes was expressed quantitatively as a quadratic function of lipophilicities of the terpenes, measured as a lipophilic index. Further increase in the significant level was observed when the molecular weight of terpenes was included in this function as the second factor. The synergism of ethanol with d-limonene, selected from among the other terpenes, on the promoting activity was statistically investigated. It was evident that both d-limonene and ethanol were important factors for promoting the percutaneous absorption of indomethacin. A significant synergism of d-limonene with ethanol was also observed. As a possible mechanism for enhancement action of d-limonene and ethanol, it was considered that, at first, d-limonene penetrates into the skin under coexistence with ethanol and may change the barrier structure of the stratum corneum. The transfer of ethanol to the skin is thereby enhanced under the coexistence with d-limonene in the skin. Thus, the permeation of indomethacin can be promoted due to its affinity with ethanol.     

Release of benzimidazole and benzylidene camphor from topical sunscreen formulations

Absorption of two ultraviolet (UV) filters was evaluated through a lipophilic synthetic membrane (Folioxane®) and excised hairless rat skin using a flow-through diffusion cell. Folioxane membrane is an artificial skin used in the treatment of third-degree burns. Diffusion tests were performed with aqueous solutions and galenic formulations (one water-in-oil [W/O] emulsion and two oily gels). Analyses were achieved with high-performance liquid chromatography (HPLC) with UV detection at 295 nm. Diffusion kinetics of 17 β estradiol, a reference compound, through rat skin, human skin, and Folioxane membrane were performed to validate the in vitro model. Phenylbenzimidazole and methylbenzylidene camphor in aqueous solutions were diffused at a regular rate through the Folioxane film. The release of phenylbenzimidazole was very slow, whereas the release of benzylidene camphor was more pronounced: a decrease of the quantity was observed in the donor compartment (30 % at 6 hr and 93% after 72 hr). A significant flow of benzylidene camphor was also measured through excised skin of rat in the first 3 hr. The skin absorption was 38% over 72 hr. The W/O emulsion had low penetration of UV filter: 20% of the initial amount for Folioxane membrane and 0.4% for rat skin. In contrast, the penetration of two oily gels was identical: 28% on Folioxane membrane and 0.6% on rat skin. This study demonstrates the transcutaneous diffusion of two important classes of sunscreens through a lipophilic Folioxane membrane and through excised hairless rat skin. From the results, Folioxane membrane appears to be an alternative model for studying diffusion of topical molecules and as a tool for guiding formulation choices.     

Limonene and Related Compounds as Potential Skin Penetration Promoters

Abstract

A transdermal therapeutic system can be developed by promoting the skin permeability of drugs with some materials. In this study, the promoting effect of terpenes present in essential oils on the percutaneous absorption of indomethacin from alcoholic hydrogels was investigated in rats in vivo. The enhancing activity of terpenes was expressed quantitatively as a quadratic function of lipophilicities of the terpenes, measured as a lipophilic index. Further increase in the significant level was observed when the molecular weight of terpenes was included in this function as the second factor. The synergism of ethanol with d-limonene, selected from among the other terpenes, on the promoting activity was statistically investigated. It was evident that both d-limonene and ethanol were important factors for promoting the percutaneous absorption of indomethacin. A significant synergism of d-limonene with ethanol was also observed. As a possible mechanism for enhancement action of d-limonene and ethanol, it was considered that, at first, d-limonene penetrates into the skin under coexistence with ethanol and may change the barrier structure of the stratum corneum. The transfer of ethanol to the skin is thereby enhanced under the coexistence with d-limonene in the skin. Thus, the permeation of indomethacin can be promoted due to its affinity with ethanol.     

铝合金-聚合物复合层板弯曲回弹理论分析

针对铝合金-聚合物复合层板弯曲回弹问题,分析了复合层板弯曲过程表面层铝板及中心层聚合物的变形特征,建立了复合层板平面应变纯弯曲回弹理论分析模型.采用建立的模型预测了复合层板纯弯曲过程回弹角变化,并与实验结果进行了对比,分析了聚合物层厚度及铝合金板材力学性能对回弹的影响规律.结果表明:随着中心聚合物层厚度的增加,复合层板回弹角降低;随着表面层铝板强度的降低,复合层板回弹角减小.理论预测结果与实验结果一致,说明了本文推导的理论模型的可靠性.     

Experimental investigation of compression failure of sandwich specimens with face/core debond

An experimental study of the in-plane compressive failure mechanism of foam cored sandwich specimens with an implanted through-width face/core debond is presented. Tests were conducted on sandwich specimens with glass/vinylester and carbon/epoxy face sheets over various PVC foam cores. Observation of the response of the specimens during testing showed that failure occurred by buckling of the debonded face sheet, followed by rapid debond growth towards the ends of the specimen. The compression strength of the sandwich specimens containing a debond decreased quite substantially with increasing debond size. A high-density core resulted in less strength decrease at any given debond size. Examination of the failure surfaces after separation of the face sheet and core revealed traces of core material deposited on the face sheet evidencing cohesive core failure. The amount of core material adhered to the face sheet decreased with increasing foam density indicating increasing tendency for core/resin interfacial failure.     

Comparison of Skin Permeation of Dideoxynucleoside-Type Anti-HIV Drugs: Alone Versus Combination

The effects of vehicles and skin permeation enhancer on the skin permeation of dideoxynucleoside-type anti-HN drugs, Zalcitabine (DDC), Didanosine (DDI), and Zidovudine (AZT), alone and in combination, were compared using hairless rat and human cadaver skins. Each drug alone or a combination of three drugs was added to various compositions of ethanol/water or ethanol/tricaprylin cosolvent system to saturation, and in vitro skin permeation studies were conducted using Valia-Chien skin permeation cells. In both ethanol/water and ethanol/tricaprylin systems, the hairless rat skin permeation rates achieved by each drug alone and three drugs in combination were not significantly different. Addition of oleic acid [1.0% (v/v) for each drug alone and 5.0% (v/v) for drug combination] in ethanol/tricaprylin (50:50) could not significantly enhance the skin permeation of these drugs. In hairless rat skin permeation of each drug alone, the permeation rates of all three drugs were dramatically enhanced with the addition of oleic acid in ethanol/water (60:40) cosolvent system and reached plateau level with oleic acid as low as 0.3% (v/v). However, in the case of drug combination, the enhancement of skin permeation rates of these drugs with the addition of oleic acid in ethanol/water (80:20) cosolvent system was not as high as that observed for each drug alone, and plateau level was not observed even at 5.0% (v/v) of oleic acid. Human cadaver skin permeation rates of each drug alone saturated in ethanol/ water (60:40) cosolvent system containing 1.0% (v/v) of oleic acid were 3-4 times lower than those of hairless rat skin. However, in skin permeation of three drugs in combination, saturated in ethanol/water (80:20) cosolvent system containing 5.0% (v/v) of oleic acid, human cadaver skin permeation rates of DDC and DDI were slightly lower than those of hairless rat skin, and there was no significant difference between the two skins for AZT. These results show that mutual skin permeation-enhancing effects of oleic acid and an ethanol/water cosolvent system Made the transdermal delivery of anti-HIV drugs, alone and in combination, feasible.     

Electroless copper plating on 1,2-ethylenediamine grafted poly(ethyleneterepthalate) for the fabrication of flexible copper clad laminate

An efficient method for the fabrication of flexible copper clad laminate (FCCL) on poly(ethyleneterepthalate) (PET) sheet by electroless plating was developed. This method relies on PET surface grafted 1,2-ethylenediamine (EDA) layer, which is employed as an adhesive interlayer for the manufacture of FCCL. Au catalysts were adsorbed on the EDA treated PET sheet and subsequently initiate the deposition of copper in an electroless plating solution. Attenuated total reflection fourier transformation infrared (ATR-FT-IR) spectroscopy, water contact angle, X-ray photoelectron spectroscopy, and atomic force microscope were employed to trace the surface changes during the grafting process with water, ethanol or dimethyl sulfoxide (DMSO) as solvent. For the PET sheets grafted from ethanol and DMSO solution, the prepared copper layers show strong adhesion to the substrate, which can pass Scotch^® tape test, while the sample grafted from water solution fail. All results indicate that using ethanol or DMSO as solvent for EDA grafting is benefit for the preparation of FCCL, and the adhesive improvements are due to an increase in the surface roughness of PET sheets and the amount of gold particles adsorbed on PET surface which act as nucleation and anchor sites for copper.     

Bicontinuous water-AOT/Tween85-isopropyl myristate microemulsion: a new vehicle for transdermal delivery of cyclosporin A

The purpose of this study was to investigate the influence of structure and composition of microemulsions (AOT/Tween85/isopropyl myristate/water) on their transdermal delivery potential of a lipophilic model drug (Cyclosporin A), and to compare the drug delivery potential of microemulsion to the suspension of drug in normal saline containing 20% ethanol. Their type and structure were examined by measuring surface tension, density, viscometry, and electric conductivity; the degree of agreement between the techniques was assessed. Transdermal flux of Cyclosporin A through rat skin was determined in vitro using Franz-type diffusion cells. Results of conducting, viscosity, and surface tension measurement confirmed the prediction transition to a bicontinuous structure. The microemulsions increased transdermal drug delivery of Cyclosporin A up to 10 times compared to the suspension. The increased transdermal delivery was found to be due mainly to water concentration and appeared to be dependent on the structure of the microemulsions.     

Comparison of Skin Permeation of Dideoxynucleoside-Type Anti-HIV Drugs: Alone Versus Combination

Abstract

The effects of vehicles and skin permeation enhancer on the skin permeation of dideoxynucleoside-type anti-HN drugs, Zalcitabine (DDC), Didanosine (DDI), and Zidovudine (AZT), alone and in combination, were compared using hairless rat and human cadaver skins. Each drug alone or a combination of three drugs was added to various compositions of ethanol/water or ethanol/tricaprylin cosolvent system to saturation, and in vitro skin permeation studies were conducted using Valia-Chien skin permeation cells. In both ethanol/water and ethanol/tricaprylin systems, the hairless rat skin permeation rates achieved by each drug alone and three drugs in combination were not significantly different. Addition of oleic acid [1.0% (v/v) for each drug alone and 5.0% (v/v) for drug combination] in ethanol/tricaprylin (50:50) could not significantly enhance the skin permeation of these drugs. In hairless rat skin permeation of each drug alone, the permeation rates of all three drugs were dramatically enhanced with the addition of oleic acid in ethanol/water (60:40) cosolvent system and reached plateau level with oleic acid as low as 0.3% (v/v). However, in the case of drug combination, the enhancement of skin permeation rates of these drugs with the addition of oleic acid in ethanol/water (80:20) cosolvent system was not as high as that observed for each drug alone, and plateau level was not observed even at 5.0% (v/v) of oleic acid. Human cadaver skin permeation rates of each drug alone saturated in ethanol/ water (60:40) cosolvent system containing 1.0% (v/v) of oleic acid were 3-4 times lower than those of hairless rat skin. However, in skin permeation of three drugs in combination, saturated in ethanol/water (80:20) cosolvent system containing 5.0% (v/v) of oleic acid, human cadaver skin permeation rates of DDC and DDI were slightly lower than those of hairless rat skin, and there was no significant difference between the two skins for AZT. These results show that mutual skin permeation-enhancing effects of oleic acid and an ethanol/water cosolvent system Made the transdermal delivery of anti-HIV drugs, alone and in combination, feasible.     

Effect of Application Volume of Ethanol-Isopropyl Myristate Mixed Solvent System on Permeation of Zidovudine and Probenecid Through Rat Skin

Permeation of zidovudine (AZT) and probenecid from an ethanol-isopropyl myristate (IPM) mixed system through rat skin was studied in a finite system. Several volume sizes of the ethanol-IPM mixed systems containing AZT and probenecid, both as suspensions, were applied on the skin of the hairless rat using a vertical glass cell, and the fractions of the drugs permeated in 8 hr Q_%,8hr were determined. For the systems containing 40% ethanol, the Q_%,8hr value decreased with the reduction of volume of the system applied, and the decreasing profile was similar to that calculated on the assumption that the permeability of the drug does not change with the volume of the sample applied. On the other hand, in the systems containing 10% or 20% ethanol, the Q_%,8hr value showed a maximum when a specific volume of the sample was applied. Therefore, the effect of sample volume on the Q_%,8hr value was different between the 40% ethanol-IPM system and the 10% or 20% ethanol-IPM system. Following pretreatment of the skin with 0.105 ml/cm² of drug-free 40% ethanol-IPM for 2 hr, several volume sizes of 10% ethanol-IPM systems containing the drugs were applied on the skin to explain why the different profiles were observed in the system containing 10% or 20% ethanol. The results for pretreated skin suggest that the amount of ethanol in the systems with low ethanol concentration and small application volume is too small to exert an effect that enhances permeation of the drugs. In those systems, the integrated effect of ethanol on the skin would be important for the enhancing effect. Total volume, as well as concentration, of an enhancer should be set precisely in designing an efficient transdermal delivery system.     

Effect of application volume of ethanol-isopropyl myristate mixed solvent system on permeation of zidovudine and probenecid through rat skin

Permeation of zidovudine (AZT) and probenecid from an ethanol-isopropyl myristate (IPM) mixed system through rat skin was studied in a finite system. Several volume sizes of the ethanol-IPM mixed systems containing AZT and probenecid, both as suspensions, were applied on the skin of the hairless rat using a vertical glass cell, and the fractions of the drugs permeated in 8 hr Q_%,8hr were determined. For the systems containing 40% ethanol, the Q_%,8hr value decreased with the reduction of volume of the system applied, and the decreasing profile was similar to that calculated on the assumption that the permeability of the drug does not change with the volume of the sample applied. On the other hand, in the systems containing 10% or 20% ethanol, the Q_%,8hr value showed a maximum when a specific volume of the sample was applied. Therefore, the effect of sample volume on the Q_%,8hr value was different between the 40% ethanol-IPM system and the 10% or 20% ethanol-IPM system. Following pretreatment of the skin with 0.105 ml/cm² of drug-free 40% ethanol-IPM for 2 hr, several volume sizes of 10% ethanol-IPM systems containing the drugs were applied on the skin to explain why the different profiles were observed in the system containing 10% or 20% ethanol. The results for pretreated skin suggest that the amount of ethanol in the systems with low ethanol concentration and small application volume is too small to exert an effect that enhances permeation of the drugs. In those systems, the integrated effect of ethanol on the skin would be important for the enhancing effect. Total volume, as well as concentration, of an enhancer should be set precisely in designing an efficient transdermal delivery system.     

Evaluation of salicylic acid fatty ester prodrugs for UV protection

The purpose of this study was to investigate the physicochemical properties and in vitro evaluation of fatty ester prodrugs of salicylic acid for ultraviolet (UV) protection. The physicochemical properties such as lipophilicity, chemical stability and enzymatic hydrolysis were investigated with the following fatty ester prodrugs of salicylic acid: octanoyl (C8SA), nonanoyl (C9SA), decanoyl (C10SA), lauroyl (C12SA), myristoyl (C14SA) and palmitoyl oxysalicylate (C16SA). Furthermore, their skin permeation and accumulation were evaluated using a combination of common permeation enhancing techniques such as the use of a lipophilic receptor solution, removal of stratum corneum and delipidization of skin. Their k' values were proportional to the degree of carbon-carbon saturation in the side chain. All these fatty esters were highly stable in 2-propanol, acetonitrile and glycerin, but unstable in methanol and ethanol. They were relatively unstable in liver and skin homogenates. In particular, C16SA was mostly hydrolyzed to its parent compound in hairless mouse liver and skin homogenates, suggesting that it might be converted to salicylic acid after its topical administration. In the skin permeation and accumulation study, C16SA showed the poorest permeation in all skins, suggesting that it could not be permeated in the skin. Furthermore, C14SA and C16SA were less accumulated in delipidized skin compared with normal skin or stripped skin, suggesting that these esters had relatively strong affinities for lipids compared with the other prodrugs in the skin. C16SA showed significantly higher dermal accumulation in all skins compared with its parent salicylic acid. Thus, the palmitoyl oxysalicylate (C16SA) might be a potential candidate for UV protection due to its absence of skin permeation, smaller uptake in the lipid phase and relatively lower skin accumulation.     

Stacked polypyrrole-coated non-woven fabric sheets for absorbing electromagnetic waves with extremely high frequencies

Conductive non-woven fabric sheets coated with polypyrrole nanoparticles and having resistivity from 1.5 × 10⁵ to 3.0 Ω cm were prepared by immersing non-woven fabric sheets in solutions containing various concentrations of oxidizing agent and dopant and then exposing the sheets to pyrrole vapor. A stack of ten treated sheets could absorb more than 95% of electromagnetic waves in the frequency range of 75–110 GHz and more than 99% in the range of 85–105 GHz, irrespective of the resistivity of the sheet. This absorption was achieved even though the thickness of the stack was less than 10 mm. Furthermore, a conductive non-woven fabric sheet with resistivity of 7.5 Ω cm and thickness of only 0.5 mm could absorb about 90% of electromagnetic waves in the range of 75–110 GHz. These results clearly demonstrate that the stacked conductive non-woven fabric sheets prepared in this study are a new material that effectively absorbs electromagnetic waves with extremely high frequencies in the millimeter band.     

Effect of fatty acid diesters on permeation of anti-inflammatory drugs through rat skin

Four fatty acid diesters (diethyl succinate, diethyl adipate, diethyl sebacate, and diisopropyl adipate) were used to study their enhancement effect on the permeation of four non-steroidal anti-inflammatory drugs (NSAIDs: ketoprofen, indomethacin, diclofenac sodium, and ibuprofen) through rat abdominal skin. With the diester pretreatment, drug permeation increased and the lag times decreased. No relationship was observed between the solubilities of the drugs in the diesters and the diester enhancement effects. The enhancement effect decreased with an increase of the drug lipophilicity, but increased with an increase of the lipophilic index of the diester up to about 3.5, after which the enhancement effect decreased or remained constant. Attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR) was employed to investigate the biophysical changes in the stratum corneum lipids caused by the diesters. The FTIR results showed that treatment of the skin with diesters did not produce a blue shift in the asymmetric and symmetric C-H stretching peak positions. However, all of the above diesters showed a decrease in peak heights and areas for both asymmetric and symmetric C-H stretching absorbances in comparison with water treatment.

These results suggested that the diesters were more effective for enhancing the penetration of hydrophilic drugs than lipophilic drugs, and the enhancing effect of lipophilic diesters was more effective than that of hydrophilic diesters. The enhancement effects of diesters may be due to their causing lipid extraction in the skin.     

Permeation and skin retention of quercetin from microemulsions containing Transcutol® P

A microemulsion for the cutaneous release of quercetin was prepared. An aqueous phase, containing 40% Transcutol(?) P as solubilizing agent and permeation enhancer, was emulsified with Labrafil(?) as oil phase and Labrasol(?)/Capryol(?) 90 as Solvent/Co-solvent. Quercetin was dissolved in the microemulsion at the concentration of 1%. Ternary phase diagrams were generated to determine the optimal concentration of each excipient composing the microemulsion. The physicochemical properties of the microemulsion, such as pH, viscosity, refractive index, and particle size distribution were determined. The microemulsion was stable for 12 months at the storing conditions of 25.0 ± 1.0°C. The in vitro quercetin permeability into and through the abdominal hairless pig skin was determined by vertical Franz's cells. Quercetin showed hardly any permeability through the skin when dissolved in water- and Transcutol(?) P-free media, whereas a remarkable increase in cutaneous permeability was observed when quercetin was formulated in the microemulsion or when simply dissolved in Transcutol(?) P. These two last formulations are those showing the lower skin retention.     

Fatigue and fretting of mixed metal self-piercing riveted joint

The fatigue behavior of self-piercing rivet (SPR) joints joining differing thicknesses of AA6111-T4 aluminum and HSLA340 steel sheets in lap shear geometry was investigated in this paper. Crack initiation in the aluminum sheet was the dominant failure mode, while unexpected rivet shank failure tended to occur at high loading levels. Fretting wear was also observed at interface between aluminum and steel sheets as well as between the rivet and sheets under sinusoidal cyclic tension–tension loading. An Energy Dispersive X-ray (EDX) analysis of fretting debris revealed the presence of oxides of aluminum and zinc. Fretting was shown to be critical to crack initiation. For initiations in the aluminum sheet, micro cracks were found to nucleate early in the fatigue life, and crack initiation life was found to be much shorter than crack growth life.     

Effect of Fatty Acid Diesters on Permeation of Anti-Inflammatory Drugs Through Rat Skin

ABSTRACT

Four fatty acid diesters (diethyl succinate, diethyl adipate, diethyl sebacate, and diisopropyl adipate) were used to study their enhancement effect on the permeation of four non-steroidal anti-inflammatory drugs (NSAIDs: ketoprofen, indomethacin, diclofenac sodium, and ibuprofen) through rat abdominal skin. With the diester pretreatment, drug permeation increased and the lag times decreased. No relationship was observed between the solubilities of the drugs in the diesters and the diester enhancement effects. The enhancement effect decreased with an increase of the drug lipophilicity, but increased with an increase of the lipophilic index of the diester up to about 3.5, after which the enhancement effect decreased or remained constant. Attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR) was employed to investigate the biophysical changes in the stratum corneum lipids caused by the diesters. The FTIR results showed that treatment of the skin with diesters did not produce a blue shift in the asymmetric and symmetric C–H stretching peak positions. However, all of the above diesters showed a decrease in peak heights and areas for both asymmetric and symmetric C–H stretching absorbances in comparison with water treatment.

These results suggested that the diesters were more effective for enhancing the penetration of hydrophilic drugs than lipophilic drugs, and the enhancing effect of lipophilic diesters was more effective than that of hydrophilic diesters. The enhancement effects of diesters may be due to their causing lipid extraction in the skin.     

Bicontinuous Water-AOT/Tween85-Isopropyl Myristate Microemulsion: A New Vehicle for Transdermal Delivery of Cyclosporin A

ABSTRACT

The purpose of this study was to investigate the influence of structure and composition of microemulsions (AOT/Tween85/isopropyl myristate/water) on their transdermal delivery potential of a lipophilic model drug (Cyclosporin A), and to compare the drug delivery potential of microemulsion to the suspension of drug in normal saline containing 20% ethanol. Their type and structure were examined by measuring surface tension, density, viscometry, and electric conductivity; the degree of agreement between the techniques was assessed. Transdermal flux of Cyclosporin A through rat skin was determined in vitro using Franz-type diffusion cells. Results of conducting, viscosity, and surface tension measurement confirmed the prediction transition to a bicontinuous structure. The microemulsions increased transdermal drug delivery of Cyclosporin A up to 10 times compared to the suspension. The increased transdermal delivery was found to be due mainly to water concentration and appeared to be dependent on the structure of the microemulsions.     

Elastic-plastic analysis of a finite sheet with a cold-worked hole

An exact elastic-plastic solution has been obtained for the residual stress and strain field in a finite circular sheet having a cold-worked or interference fitted hole on the basis of J₂ deformation theory together with a modified Ramberg-Osgood law. Many factors influencing the residual stresses are analysed. Comparison with finite element results and experimental data for rectangular sheets containing cold-worked holes is made. It is shown that the solution of a finite circular sheet can be used to predict the residual stresses on the minimum cross section in a rectangular sheet with a cold-worked hole fast and effectively, so long as the diameter of the circular sheet is equal to the width of the sheet.