Ethylene Vinyl Acetate Matrix Research Articles

Enhanced Controlled Transdermal Delivery of Hydrochlorothiazide from an Ethylene-vinyl Acetate Matrix

ABSTRACT Š Repeated oral adm inistration of hy drochlorothiazide, a loop diuretic, due to transient high blood levels, m aycause adverse effects such as gastric disturbance, nausea, high blood sugar, and hy per lipidem ia. Transderm al adm inistrationcould avoid som e of these sy stemic side eff ects and gastric disorders. We have developed a m atrix using ethylene-viny l ace-tate (EVA ), a heat-processible and flexible m aterial, for transdermal delivery of hydrochlorothiazide. Drug solubility washighest at 40% PEG -400 volume fraction. Drug release increased as concentration increased w ith a linear relationshipbetween the release rate and the square root of loading dose. Increasing tem perature increased drug release f rom the EVAmatrix. The activation energy, measured from the slope of log P versus 1000/T, was 11.9 kcal/m ol for a 2.5% loading dosefrom EVA matrix. Diethy l phthalate had the highest plasticizing effects on the release of hydrochlorothiazide. To increasethe skin permeation of hy drochlorothiazide from theA EV m atrix, enhancers such as the saturated fatty acids, the unsaturatedfatty acids, and the non-nicoi surfactants w ere aded to thed A m EVatrix, an sdk nepi rmeatnoi w as evaluated using a modifiedKeshary -Chien diffusion cell fitted with intact excised rat skin. Polyoxy ethy lene 23-laury l ether showed the highest enhanc-ing eff ects. In conclusion, transderm al delivery of hy drochlorothiazide could be improved from an EVA m atrix containingplasticizer and perm eation enhancer.Key words

Thermophysical and Electrical Properties of Nanocomposites Based on Ethylene–Vinylacetate Copolymer (EVA) Filled with Expanded and Unexpanded Graphite

Over the last few years, conducting polymer/graphite nanocomposites have attracted considerable interest because of their exceptional electrical, thermal, and mechanical properties. Polymeric nanocomposites prepared from high aspect ratio layered graphite nanofillers achieve significant improvements in thermophysical and electrical properties at low filler concentrations, compared to conventional composites, without a significant increase in density. In this work, various aspects of the electrical and thermophysical behavior of nanocomposites are presented based on the ethylene–vinylacetate matrix filled with nanostructured expanded graphite and standard, (nano)/micro-sized graphite.

Enhanced Bioavailability of Ambroxol by Transdermal Administration of the EVA Matrix Containing Penetration Enhancer in Rats

The pharmacokinetics and bioavailability of ambroxol, an expectoration improver and mucolytic agent, were studied to determine the feasibility of enhanced transdermal delivery of ambroxol from the ethylene-vinyl acetate (EVA) matrix system containing polyoxyethylene-2-oleyl ether as an enhancer in rats. The ambroxol-010 matrix system (15 mg/kg) was applied to abdominal skin of rats. Blood samples were collected via the femoral artery for 28 hrs and the plasma concentrations of ambroxol were determined by HPLC. Pharmacokinetic parameters were calculated using Lagran method computer program. The area under the curve (AUC) was significantly higher in the enhancer group (1,678 ± 1,413.3 ng/ml·hr) than that in the control group 1,112 ± 279 ng/mlㆍhr), that is treated transdermally without enhancer, showing about 151% increased bioavailability (p<0.05). The average Cmax was increased in the enhancer group (86.0 ± 21.5 ng/ml) compared with the control group (59.0 ± 14.8 ng/ml). The absolute bioavailability was 13.9% in the transdermal control group, 21.1% in the transdermal enhancer group and 18.1% in the oral administration group compared with the IV group. The Tmax, Ka, MRT and t1/2 of ambroxol in transdermal enhancer group were increased significantly (p<0.01) compared to those of oral administration. As the ambroxol-EVA matrix containing polyoxyethylene-2-oleyl ether and tributyl citrate was administered to rats via the transdermal routes, the relative bioavailability increased about 1.51-fold compared to the control group, showing a relatively constant, sustained blood concentration. The results of this study show that ambroxol-EVA matrix could be developed as a transdermal delivery system providing sustained plasma concentration.

Enhanced transdermal controlled delivery of glimepiride from the ethylene-vinyl acetate matrix

An ethylene-vinyl acetate (EVA) matrix containing glimepiride was prepared as a potential transdermal drug delivery system. Permeation studies of quinupramine through the EVA copolymer membrane were carried out using a two-chamber diffusion cell. The rate of drug permeation through the EVA membrane was proportional to the PEG 400 volume fraction. The release of glimepiride from the EVA matrix was examined using a modified Franz diffusion cell. A plasticizer was added to prepare the pore structure of the EVA matrix in order to increase the rate of drug release. The effects of PEG 400, drug concentration, temperature, and plasticizer on the drug release rate were investigated. Various types of enhancers were added to an EVA matrix containing 2% glimepiride in an attempt to increase the level of skin permeation of quinupramine through an EVA matrix. The effects of the enhancers on the level of glimepiride permeation through the skin were evaluated using Franz diffusion cells fitted with intact excised rat skin. The rate of drug release from the EVA matrix increased with increasing PEG 400 volume fraction, temperature, and drug loading. The estimated activation energy of drug release was 7.274 kcal/mol for 2% drug loading dose. The release of glimepiride from the EVA matrix followed a diffusion-controlled model, where the quantity released per unit area was proportional to the square root of time. The controlled release of glimepiride was achieved using the EVA polymer including the plasticizer. Among the plasticizers used, such as the alkyl citrates and phthalates groups, diethyl phthalate slightly increased the rate of glimepiride release. Among the various enhancers used, such as the non-ionic surfactants, the glycerides, the propylene glycol derivatives, fatty acids (saturated or unsaturated), and pyrrolidones, linoleic acid showed the highest permeation rate; 3.17-times higher than the control. In conclusion, an EVA matrix containing a permeation enhancer can be used for the transdermal controlled delivery of glimepiride.

Enhanced transdermal absorption and pharmacokinetic evaluation of pranoprofen-ethylene-vinyl acetate matrix containing penetration enhancer in rats

To increase the skin permeation of pranoprofen from the ethylene-vinyl acetate (EVA) matrix, different types of enhancers were added to an EVA matrix containing 2% pranoprofen. The pharmacokinetics and bioavailability of pranoprofen, an anti-inflammatory drug, were examined to determine the feasibility of an enhanced transdermal delivery system for pranoprofen from an EVA matrix containing caprylic acid as the enhancer in rats. The effects of the enhancers on the level of pranoprofen permeation through the skin were evaluated using Franz diffusion cells that were fitted with the intact excised rat skin. Among the enhancers used, including the fatty acids (saturated, unsaturated), the glycols, the glycerides, and the pyrrolidones, caprylic acid showed the best enhancement. A pranoprofen-EVA matrix system was formulated containing caprylic acid as an enhancer. The pranoprofen-EVA matrix system (8 mg/kg) was applied to the abdominal skin of rats. The blood samples were collected through the femoral artery for 24 h and the plasma concentrations of pranoprofen were determined by HPLC. The pharmacokinetic parameters were calculated using the MULTI computer program. The area under the curve (AUC) was significantly higher in the enhancer group (55.49 +/- 13.87 ng/mL.h) than in the control group (22.48 +/- 5.63 ng/mL.h), which was treated transdermally without the enhancer, showing about 246% increased bioavailability (p<0.05). As the pranoprofen-EVA matrix containing caprylic acid as an enhancer was administered to rats via the transdermal routes, the relative bioavailability increased about 2.46-fold compared to the control group, showing a relatively constant, sustained blood concentration. These results show that a pranoprofen-EVA matrix containing a permeation enhancer could be developed as a transdermal delivery system to provide a sustained plasma concentration.

Enhanced Transdermal Delivery of Furosemide from the EVA Matrix through the Rat Skin

This study was performed to examine the possibility of increasing the level of furosemide permeation from the ethylene-vinyl acetate (EVA) matrix through the skin by incorporating various enhancers in the EVA matrix. The effects of the enhancers on the level of furosemide permeation through the skin were evaluated using Franz diffusion cells with intact excised rat skins. The enhancers examined were the fatty acids (saturated, unsaturated), the pyrrolidones, the propylene glycol derivatives, the glycerides and the non-ionic surfactants. Among the enhancers used, polyoxyethylene-2-oleyl ether (a non-ionic surfactant) showed the best enhancement. The polyoxyethylene 2-oleyl ether as a permeation enhancer could be used for development of furosemide-EVA transdermal matrix system.

Enhanced Controlled Release of Loratadine From the Ethylene-vinyl Acetate Matrix Containing Plasticizer

An ethylene-vinyl acetate (EVA) matrix containing plasticizer was prepared as a potential controlled release system for loratadine. The EVA matrix containing loratadine was prepared as the transdermal device using casting methods. The solubility of loratadine according to the volume fraction of PEG 400 was determined. The effects of the drug concentration, temperature, and plasticizers on the release of the drug were determined at 37°C using 40% PEG 400 solution as the receptor medium using the modified Keshary-Chien cell. Some types of plasticizers. such as citrates and phthalates, were used to prepare the pores and increase the flexibility of the EVA matrix. The solubility test according to the PEG 400 volume fraction revealed the highest solubility in the 40% PEG 400 solution. The rate of drug released from the EVA matrix increased with increasing temperature and drug loading. There was a linear relationship between the release rate and the square root of the loading dose. The activation energy for drug release from the EVA matrix with a loading dose of 1%, 2%, 3%, 4%, and 5% was estimated to be 6.83, 6.80, 6.77, 6.71, and 6.65 kcal/mol, respectively Among the plasticizers used, diethyl phthalate showed the highest level of loratadine release. In conclusion, an EVA matrix containing plasticizer could be used to enhance the controlled release of loratadine.

Synergistic effects of layered double hydroxide with hyperfine magnesium hydroxide in halogen-free flame retardant EVA/HFMH/LDH nanocomposites

The synergistic effects of layered double hydroxide (LDH) with hyperfine magnesium hydroxide (HFMH) in halogen-free flame retardant ethylene-vinyl acetate (EVA)/HFMH/LDH nanocomposites have been studied by X-ray diffraction (XRD), transmission electron spectroscopy (TEM), thermogravimetric analysis (TGA), limiting oxygen index (LOI), mechanical properties' tests, and dynamic mechanical thermal analysis (DMTA). The XRD results show that the exfoliated EVA/HFMH/LDH can be obtained by controlling the LDH loading. The TEM images give the evidence that the organic-modified LDH (OM-LDH) can act as a disperser and help HFMH particles to disperse homogeneously in the EVA matrix. The TGA data demonstrate that the addition of LDH can raise 5–18 °C thermal degradation temperatures of EVA/HFMH/LDH nanocomposite samples with 5–15 phr OM-LDH compared with that of the control EVA/HFMH sample when 50% weight loss is selected as a point of comparison. The LOI and mechanical tests show that the LDH can act as flame retardant synergist and compatilizer to apparently increase the LOI and elongation at break values of EVA/HFMH/LDH nanocomposites. The DMTA data verify that the T g value (−10 °C) of the EVA/HFMH/LDH nanocomposite sample with 15 phr LDH is much lower than that ( T g = −2 °C) of the control EVA/HFMH sample without LDH and approximates to the T g value (−12 °C) of pure EVA, which indicates that the nanocomposites with LDH have more flexibility than that of the EVA/HFMH composites.

Effects of Organoclay Loading and Ethylene Glycol on Mechanical, Morphology and Thermal Properties of Ethylene Vinyl Acetate/Organoclay Nanocomposites

Effects of organoclay loading (organophilic modified montmorillonite with octadecylamine) on the processing properties, tensile properties, morphology, thermal stability and water absorption behavior of ethylene vinyl acetate (EVA)/organoclay nanocomposites were studied. Organoclay loading from 2 to 10 phr was used as a filler in this study. The EVA/organoclay nanocomposites were produced using the melt compounding technique in an internal mixer, Haake Rheometer, at 120°C and 50 rpm of rotor speed. Ethylene glycol was used to compatibilize the polymer matrix-filler system. The ethylene glycol loading was maintained at 2 phr for all compounding systems. The results indicate that the processing torque increases gradually from 0 to 10 phr of organoclay loading. The tensile strength increases at 2 phr organoclay loading. Young's modulus increases with increasing organoclay loading which slightly reduces the elongation at break. The 2 phr of organoclay loading also showed better thermal stability and less water absorption. These enhanced properties are due to the homogenous dispersion of individual silicate layers in EVA matrix, which is evidenced from the structure that evaluated using X-ray diffraction (XRD), transmission electron microscopy (TEM) and scanning electron microscopy (SEM). This exfoliation was achieved without the addition of compatibilizer. Interestingly, the presence of ethylene glycol reduces the processing torque, improves the tensile strength, elongation at break, and thermal stability of the EVA/organoclay nanocomposites.

Development and Biopharmaceutical Evaluation of Quinupramine-EVA Matrix Containing Penetration Enhancer for the Enhanced Transdermal Absorption in Rats

To increase the skin permeation of quinupramine through the rat skin, different types of enhancers were added to an ethylene-vinyl acetate (EVA) matrix containing 2% quinupramine. The effects of the enhancers on the level of quinupramine permeation through the skin were evaluated by using Franz diffusion cells that were fitted with the intact excised rat skin. Among the enhancers used, which included fatty acids (saturated and unsaturated), glycerides, pyrrolidones, and nonionic surfactants, polyoxyethylene-2-oleyl ether showed the best enhancement. The pharmacokinetics and bioavailability of quinupramine from an EVA matrix were examined to determine the level of percutaneous absorption in rats. The percutaneous absorption of quinupramine from the EVA matrix with or without an enhancer was investigated. Quinupramine was administered orally or intravenously to compare the pharmacokinetic parameters with that of the transdermal route. The relative bioavailability of quinupramine in the matrix containing polyoxyethylene-2-oleyl ether as an enhancer was approximately 2.81 times higher than the group without an enhancer. Histological examination revealed that the skin pretreated with the EVA matrix containing the enhancers had a loosely layered stratum corneum. These results show that the quinupramine-EVA matrix containing a permeation enhancer could be a good transdermal delivery system for providing sustained plasma concentrations.

Controlled Release of Pranoprofen from the Ethylene-Vinyl Acetate Matrix Using Plasticizer

ABSTRACTAn ethylene-vinyl acetate (EVA) matrix containing pranoprofen was prepared using the casting method and the release patterns of pranoprofen were observed. The solubility of pranoprofen was determined to be a function of the volume fraction of polyethylene glycol 400. The release of the drug from the matrix was examined as a function of temperature and drug concentration. Plasticizers such as the citrates and the phthalates were added to prepare the membrane in order to increase the flexibility of the EVA matrix. The solubility of pranoprofen was the highest when the PEG 400 concentration was 20% (v/v). The rate of drug release from the EVA matrix increased with increasing temperature and drug loading dose. There was a linear relationship between the flux of pranoprofen and the square root of the loading dose. The activation energy of release (Ea), which was measured from the slope of the log P versus 1000/T plots, was estimated to be 17.44, 16.14, 14.88, and 14.78 kcal/mol for loading doses of 0.5, 1, 1.5, and 2%, respectively. Among the plasticizers used such as the citrate and the phthalate groups, diethyl phthalate had the best enhancing effects on drug release. In conclusion, the application of an EVA matrix containing a plasticizer might be useful in the development of a controlled drug delivery system.

Preparation and Properties of Ethylene Vinyl Acetate (EVA)/Organoclay/Compatibilizer Nanocomposites: Effects of Organoclay Loading and Methyl Ethyl Ketone

Ethylene vinyl acetate (EVA)/organoclay/compatibilizer nanocomposites were produced using a melt compounding technique in an internal mixer, Haake Rheometer, at 120°C and 50 rpm rotor speed. Effects of organoclay loading (from 2 to 10 phr—parts per hundred of resin and methyl ethyl ketone (MEK), used as a compatibilizer, on the processing properties, tensile properties, morphology, thermal degradation, and water absorption behavior of EVA/organoclay nanocomposites were studied. Results indicate that the presence of organoclay increase the processing torque, tensile properties, thermal degradation, and resistance to water absorption. The optimum organoclay loading was achieved at 2 phr. This was caused by the dispersion state of individual silicate layers (intercalation/exfoliation) in EVA matrix. The intercalation/exfoliation structure affects the properties of EVA/organoclay nanocomposites as evidenced from the morphology studies such as x-ray diffraction (XRD) and transmission electron microscopy (TEM) evaluation. The addition of MEK has the ability to improve the tensile properties, thermal degradation, and slightly reduces the resistance of water permeation of EVA/organoclay nanocomposites. The enhanced properties were seen as a result of the better matrix and filler interaction. The EVA/organoclay/MEK nanocomposites shows better intercalation/exfoliation of individual silicate layers in the EVA matrix as indicated by TEM. Moreover, the XRD evaluation shows that intercalation/exfoliation of the organoclay was formed in the EVA matrix.

Electrical properties of EVA filled by zinc powder

Elastic composites of zinc powder directly dispersed within an EVA (ethylene-vinyl acetate) matrix were prepared by a hot plates procedure. Conductance of samples depends on the filler content in three different regimes: polarization, tunnelling effect and percolation. The surface corrosion was monitored by means of optical, SEM and EDX methods, and after that the loss of mass was checked. The corrosion only affects to the zinc particles placed of the surface of the composite samples.

Molecular transport of aliphatic hydrocarbons through styrene butadiene rubber/ethylene vinyl acetate blends

AbstractPolymer blends based on styrene butadiene rubber and ethylene vinyl acetate (EVA) were prepared. The sorption and diffusion of four aliphatic hydrocarbons through the blends were investigated with temperatures of 26–56°C. Sulfur, dicumyl peroxide (DCP), and a mixed system consisting of sulfur and DCP (mixed) were used as crosslinking agents for the blends. Of the three systems, the peroxide vulcanized blends were found to exhibit the lowest penetrant uptake. The aliphatic liquid penetration through the matrix decreased with an increase in the EVA content in the blends, which was attributed to the semicrystalline nature of the EVA matrix. The experimental observations were correlated with the morphology of the blends. Diffusion and permeation coefficients were calculated from the sorption data. A slight deviation from the Fickian trend was observed for the mechanism of transport with an increase in the EVA content in the blends. The molecular mass between crosslinks and thermodynamic parameters of sorption were determined from swelling data. The experimental observations were compared with different theoretical models. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 101: 2884–2897, 2006

Physicochemical characteristics of quinupramine in the EVA matrix

Ethylene-vinyl acetate (EVA) is widely used as a membrane or matrix for transdermal drug delivery systems. In an attempt to determine the state of a drug in the EVA matrix, X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR) and thermal analysis of the quinupramine–EVA matrix were carried out and the results were compared with those of a physical mixture of quinupramine and EVA at the same ratio. The 1:2 matrix of quinupramine with EVA was prepared using the casting method. The XRD pattern of the quinupramine test preparations revealed that the pure quinupramine was crystalline in nature, whereas the quinupramine in the EVA matrix was an amorphous form, which leads to increased drug release. The FT-IR spectra of quinupramine in the physical mixture showed absorption bands at around 3000–3050 cm −1 whereas these absorption bands were not observed in the quinupramine–EVA matrix. The thermal studies of quinupramine in the physical mixture showed an endothermic peak at 154–156 °C, which is the melting point of the drug, but there was no such endothermic peak observed in the EVA matrix. In conclusion, the physicochemical interactions between quinupramine and EVA, might occur at the molecular level, and that quinupramine was not crystalline in the EVA matrix.

Release characteristics of quinupramine from the ethylene–vinyl acetate matrix

An ethylene–vinyl acetate (EVA) matrix containing quinupramine was prepared in an attempt to develop a controlled delivery system for quinupramine. Permeation studies of quinupramine through the EVA copolymer membrane were carried out using a two-chamber diffusion cell. The rate of drug permeation through the EVA membrane was proportional to the PEG 400 volume fraction. The release of quinupramine from the EVA matrix was examined using a modified Franz diffusion cell. A plasticizer was added to prepare the pore structure of the EVA matrix in order to increase the rate of drug release. The effects of PEG 400, membrane thickness, drug concentration, temperature, and plasticizer on drug release rate were investigated. The drug release rate from the EVA matrix increased with increasing PEG 400 volume fraction, temperature and drug loading dose. The activation energy for drug release was 5.91, 5.39, 4.68 and 4.52 kcal/mol for a loading dose of 0.5%, 1%, 1.5%, and 2%, respectively. Among the plasticizers used, diethyl phthalate showed the best results. The release of quinupramine from the EVA matrix follows a diffusion-controlled model, where the quantity released per unit area is proportional to the square root of time. The controlled release of quinupramine was achieved using the EVA polymer including a plasticizer.

Poly(ethylene- co-vinyl acetate) copolymer matrix for delivery of chlorhexidine and acyclovir drugs for use in the oral environment: Effect of drug combination, copolymer composition and coating on the drug release rate

Objectives This study utilizes a bio-compatible ethylene vinyl acetate (EVA) copolymer to deliver drugs at therapeutic levels over extended periods of time. The release rate of an anti-fungal and an anti-microbial drug namely acyclovir (ACY) and chlorhexidine diacetate (CDA) from EVA was investigated individually and as a mixture. The effect of drug combination, the composition of the copolymer and the coating of the matrix with a different polymer on the rate of drug release are presented. Method Polymer casting solutions were prepared by homogeneously dissolving EVA copolymer and the drugs in the ratio (40:1) in dichloromethane. The drugs ACY and CDA were used individually as well as in three different weight ratios maintaining the total drug concentration in the polymer at 2.5%. Different concentrations of vinyl acetate (VA) 28, 32 and 40% in the EVA matrix were used to study the release of either ACY or CDA alone while 40% VA was used for the release study of the individual drug as well as their mixtures. Thin square films of 3 cm × 3 cm with a thickness of 0.7 mm were cut from the dry sheet obtained by solvent evaporation. Coated films were prepared by dipping ACY and CDA drug-loaded EVA films (VA 40%) into EVA copolymer of VA 32% and then dried. All of the drug-loaded samples were extracted at 37 °C in 10 ml distilled water that was replaced daily. The rate of individual drug release was measured by UV-spectrophotometer while the mixtures of drugs were measured by high performance liquid chromatography (HPLC). Results The release rate of ACY is higher than that of CDA both individually and in the ACY/CDA 50/50 mixture. In the other mixtures, the release of the drug is proportional to its concentration in the mixture. Total release of ACY is higher than CDA in most compositions. The effect of increasing the vinyl acetate content of the EVA matrix increased the drug release rate ( p = 0.02) while coating of films resulted in a decrease of the release rate of the drugs. Significance Measurements of the in vitro rate of drug release showed that there was a sustained release of drug at an almost constant concentration over extended period of time, thus providing a basis for oral treatment modality. We show that it is possible to alter the rate of drug release in the EVA matrix to a desired value by: (1) changing the composition of the EVA copolymer, (2) altering the mixtures of drugs and (3) coating the matrix with additional polymer. The use of mixtures of drugs that can enhance or decrease the rate of drug release may prove more effective in treating persistent oral infections in immunocompromised patients.

Effects of Ethylcellulose and 2-Octyldodecanol Additives on Skin Permeation and Irritation with Ethylene-Vinyl Acetate Copolymer Matrix Patches Containing Formoterol Fumarate

Skin permeation of formoterol fumarate (FF) and irritation with ethylene-vinyl acetate (EVA) copolymer matrix patches was investigated using rat and human skin in vitro and different species of experimental animal, respectively. Skin permeation of FF increased remarkably without addition of ethylcellulose (EC) and was remarkably enhanced by incorporation of 2-octyldodecanol (OD) instead of hydrogenated rosin glycerol ester (Ester Gum H). Effects on skin permeation of FF with EVA matrix patches were similar in rat and human skin, but rat skin was 1000 times more permeable than human skin after 24 h. The primary irritation indices for matrix patches without EC and with EC (OD-0), EC and 0.5 mg OD per square centimeter (OD-0.5), and EC and 1.0 mg OD per square centimeter (OD-1) were 1.46, 1.13,1.29 and 1.38. The results suggested that the irritation induced by these patches was rather mild, but significantly greater than the 0.21 observed with the control. No significant effects were noted for either EC or OD alone. Skin irritation intensity with EVA matrix patches was observed to be in the order of rabbits, guinea pigs, rats and miniature swine.

Enhanced efficacy of triprolidine by transdermal application of the EVA matrix system in rabbits and rats

The bioavailability of triprolidine from the ethylene vinyl acetate (EVA) matrix system containing polyoxyethylene-2-oleyl ether was studied to determine the feasibility of enhanced transdermal delivery of triprolidine in rabbits. The antihistamine effects were also confirmed to determine the percutaneous absorption of triprolidine from the EVA matrix system containing a penetration enhancer and plasticizer in rats. The triprolidine-EVA matrix (50 mg/kg) was applied to the abdominal skin of rabbits. Blood samples were collected via the femoral artery for 36 h and the plasma concentrations of triprolidine were determined by HPLC. The pharmacokinetic parameters were calculated using the LAGRAN computer program. The area under the curve(AUC) was significantly higher in the enhancer group (4582±1456 ng/mL h) than that (2958±997 ng/mL h) in the control group ( P<0.05), showing an approximate 155% increased bioavailability. The average C max in the enhancer group (241±46.5 ng/mL) was significantly higher than that in the control group (198±28.9 ng/mL), ( P<0.05). The mean T max in the enhancer group (8.0±2.57 h) was higher than that in the control group (6.0±2.24 h, but this was not statistically significantly. The relative bioavailability of triprolidine in the transdermal application was 35.9% in the control group and 55.6% in the enhancer group compared comparing with that after oral administration. As the triprolidine-EVA matrix, which contains polyoxyethylene-2-oleyl ether as an enhancer and triethyl citrate as a plasticizer was administered to the rabbits via the transdermal routes, the relative bioavailability increased approximately 1.55 fold compared with that in the control group, showing a relatively constant, sustained blood concentration with minimal fluctuation. The antihistamine effect was determined using the Evans blue dye procedure by comparing the changes in the vascular permeability increase following the transdermal application. The vascular permeability increase was reduced significantly by the transdermal application of the EVA-triprolidine system containing triethyl citrate and polyoxyethylene-2-oleyl ether. These results show that the plasticizer and penetration enhancer increase the skin permeation of triprolidine and the triprolidine-EVA matrix system could be developed as a transdermal delivery system providing the increased constant plasma concentration and antihistamine effects

Controlled release of furosemide from the ethylene-vinyl acetate matrix

The ethylene-vinyl acetate (EVA) matrix containing furosemide was prepared by the casting method and the release patterns were observed. The solubility of furosemide was determined as a function of volume fraction of polyethylene glycol 400. The release of drug from the matrix was studied as a function of temperature and drug concentration. Plasticizers such as the citrates and the phthalates were added for preparing the membrane to increase the flexibility of the EVA matrix. The solubility of furosemide was the highest when the concentration of PEG 400 was 40% (v/v). The release rate of drug from the EVA matrix increased with increasing temperature and drug loading doses. A linear relationship was found between the release rate and the square root of the loading dose. The activation energy ( E a), which was measured from the slope of the log P versus 1000/ T plots, was 12.33 kcal/mol for the 0.5% loading dose, and 11.58 kcal/mol for the 1.0% loading dose, and 11.00 kcal/mol for the 1.5% loading dose. Among the plasticizers used such as the citrates and the phthalates groups, diethyl phthalate showed the best enhancing effects in drug release. In conclusion, the application of an EVA matrix containing a plasticizer might be useful in the development of a controlled drug delivery system.