Ethylene-vinyl Acetate Copolymer Membrane Research Articles

Morphological control of porous ethylene-vinyl acetate copolymer membrane obtained from a co-continuous ethylene-vinyl acetate copolymer/poly(ϵ-caprolactone) blend

Ethylene-vinyl acetate copolymer (EVA)/poly(ϵ-caprolactone) (PCL) blend (50/50 w/w) with co-continuous morphology was prepared via melt mixing for fabricating microporous EVA membrane materials through selective solvent extraction. Shear flow and quiescent annealing techniques were employed to control co-continuous phase size in the EVA/PCL blend, and the time- and temperature-dependent relations of phase size were then evaluated theoretically. Using these techniques, microporous EVA membrane materials with various pore sizes ranging from 2 µm to more than 200 µm were obtained. In contrast to the porous EVA membrane prepared by the traditional way of solvent casting/particulate leaching, the as-obtained microporous membrane shows a higher level of interconnectivity and much narrower pore size distribution with uniform pore structure. © 2013 Society of Chemical Industry

The effect of isopropanol addition on enhancement of transdermal controlled release of ibuprofen from ethylene vinyl acetate copolymer membranes

AbstractThis work reports the study of the addition of isopropanol on controlled release of ibuprofen from ethylene vinyl acetate (EVAc) copolymer membranes. An EVAc solution in cyclohexane (4% w/v) containing triethyl citrate (7% w/v) as plasticizer was mixed with ibuprofen at three different concentrations of 4, 6, and 8%. Isopropanol was mixed with each of the previous mixtures to form solutions of 1, 3, and 5% isopropanol concentrations. Samples were solvent cast on glass petri‐dishes to form membranes. Home‐made diffusion cells were used for in vitro study. These cells were composed of two compartments, donor (exposed to ambient conditions), and receptor (including buffer solution maintained at 37°C). Each cell was equipped with a sampling port and water in and out system. An ultraviolet spectrometer at 222 nm was used to measure release rates of obtained membranes. The diffusion mechanism for drug release was examined by zero‐order, first‐order, Higuchi and Korsmeyer‐Peppas theories to confirm the obtained membranes follow the matrix‐type system. By increasing the drug concentration from 4 to 8%, drug release (cumulative amount) was improved from 20 (47.5%) to 30 (36%) μg/cm2 after 24 h. Addition of 5% isopropanol to the above samples (4 and 8% loading) further increased drug release to 24 and 43 μg/cm2. Results were in good agreement with the Korsmeyer‐Peppas theory for samples with 4 (% w/w) of ibuprofen. The highest percentage of drug release after 24 h was 59% for the sample with 4% drug loading compared to 50% for the sample with 8% drug loading, both with 5% isopropanol. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011

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.

Pervaporation characteristics of ethylene–vinyl acetate copolymer membranes with different composition for recovery of ethyl acetate from aqueous solution

The degree of crystallization, surface property and density of ethylene–vinyl acetate (EVA) copolymer membranes with different vinyl acetate (VA) content were measured by differential scanning calorimetry (DSC), contact angle meter and pycnometer. The pervaporation (PV) characteristics of the EVA copolymer membranes for recovery of ethyl acetate (EA) from aqueous EA solutions have been investigated. The separation factor ( α) decreased with increasing VA content from 26 wt.% (EVA26) to 100 wt.% (poly vinyl acetate, PVAc) in EVA copolymer membranes. A maximum EA flux ( J EA,max) of EVA membrane with 38 wt.% VA content revealed for 2.5 wt.% aqueous EA solution at 30 °C, J EA,max reached to 550 g/(m 2 h) and α was to 118. These PV characteristics of EVA membranes were explained in terms of the crystallinity of EVA copolymer and the affinities between EA or water and VA segment in EVA copolymer membrane. Experimental results also show that both α and J EA increased with increasing feed temperature and feed concentration.

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.

Neural network-based prediction and optimization of estradiol release from ethylene–vinyl acetate membranes

Drug-delivery systems, with predictable delivery rates, were designed using an artificial neural network-based optimization algorithm. A two-chamber diffusion cell was used to study the permeation of estradiol through ethylene–vinyl acetate copolymer membrane. The explanatory variables were the vinyl acetate (VA) content of the membrane, poly(ethylene glycol) (PEG)—solvent-composition, and membrane thickness. After deriving a neural network model to predict estradiol delivery rates as a function of these input variables, a constrained optimization procedure was applied to estimate the membrane/vehicle properties necessary to achieve a prescribed dosage. The results compared adequately well with experimental data with 71% of the data agreeing within one standard deviation. Input sensitivity analysis showed that at specific VA levels, drug delivery was more sensitive to changes in PEG compositions. The non-uniqueness of the inversion method and the accuracy of the procedure were investigated using neural network-based two-dimensional contour plots. The methodology proposed could be used to design customized polymer-based drug-delivery systems that meet specific end-user requirements.

A protective effect against undesirable increase of dihydroetorphine permeation through damaged skin by using pressure-sensitive adhesive tape with an ethylene-vinyl acetate co-polymer membrane.

The release kinetics of dihydroetorphine (DHE) from pressure-sensitive adhesive (PSA) tape with an ethylene-vinyl acetate co-polymer (EVA) membrane as a diffusion-controlling membrane and its protective effect from an unpredictable increase in skin permeation of DHE caused by stratum corneum damage were investigated. The DHE flux through the EVA membrane was enhanced with the increase of vinyl acetate content. Although the DHE release from the PSA tape was proportional to the square root of the time, the release from the PSA tape covered with the EVA membrane was dominated by zero-order rate. The release rate increased by the addition of isopropyl myristate to the PSA layer, due to the increase of solubility and diffusivity of DHE in the PSA layer, and not a decrease of permeation resistance in the EVA membrane. When using the PSA tape with the EVA membrane, the steady-state flux of DHE through hairless rat skin with stratum corneum damage was not 2-fold more than that through non-damaged skin. Plasma DHE concentration rose promptly above 5 ng/ml after the application of the PSA tape onto the damaged skin in hairless rat. In contrast, when the PSA tape with the EVA membrane was applied onto the damaged or non-damaged skin, plasma concentrations in the both cases were maintained in the therapeutic range (0.2-1.2 ng/ml). These results suggest that the PSA tape with the EVA membrane can be used to protect from the unpredictable increase in skin permeation of DHE due to stratum corneum damage.

Pervaporation of chlorinated hydrocarbon-acetone mixtures through poly(ethylene-co-vinyl acetate) membranes

Crosslinked and uncrosslinked ethylene-vinyl acetate copolymer membranes were prepared. The permeation characteristics in the pervaporation process were examined using carbon tetrachloride-acetone mixtures. Modified membranes exhibit carbon tetrachloride permselectivity, but unmodified membranes did not display the permselectivity of crosslinked polymer. Furthermore, membranes modified with dicumyl peroxide (DCP) showed a higher flux and selectivity than those of benzoyl peroxide (BP) modified ones. The effects of feed concentration, molecular size, and polarity of the permeating species on pervaporation were analyzed. The influence of crosslinking density of the membranes on pervaporation was also analyzed. The maximum separation and flux were found to be associated with an optimum amount of crosslinking agent in the membrane. A mixture of chloroform and acetone having a composition near the azeotropic region was also separated by the pervaporation technique.

Sorption of Isosorbide Dinitrate from Solution to Ethylene-Vinylacetate Copolymer Memrane. Permeation of Isosorbide Dinitrate through Ethylene-Vinylacetate Copolymer Membrane.

In ascertain the mechanism of the sorption of isosorbide dinitrate (ISDN) from the solution to the ethylene-vinylacetate copolymer (EVA) membrane, we investigated the permeation of ISDN through an EVA membrane, using a membrane permeation apparatus.The partition coefficient between the EVA membrane and water was constant around 6.3 and was not affected by temperature. It was observed that the permeation-time curve of ISDN through the EVA membrane was straight from the 4 to 7-day period, and that the amount of ISDN permeated was proportional to the time.The permeation of ISDN through the EVA membrane could be analyzed by means of a distribution-diffusion model, which provided us with a method for precisely calculating Pi, a membrane permeation coefficient. Pi depends on temperature, such that as temperature rises, it increases. For example, it increased from 7.37×10-5 (cm2·h-1) at 25°C to 1.73×10-4 (cm2·h-1) at 35°C.

Effect of pH on the Sorption of In-solution Diazepam into the Ethylene-Vinylacetate Copolymer Membrane.

We investigated the mechanism for diazepam sorptions into the ethylene-vinylacetate (EVA) copolymer membrane. A linear relationship was found between the amount of diazepam sorbed into the EVA membrane and the diazepam concentration when it was 5-20 μg/ml. The sorbed amount was influenced by pH. When the diazepam concentration in solution was 20 μg/ml, it was 0.17 mg/ g at pH 3.2 and increased to 0.74 mg/g at pH 7.0. Moreover, the experimental data showed a similar tendency as the calculated values, suggesting that the amount of diazepam sorbed was proportional to the concentration of the diazepam molecular form.

エチレン・酢酸ビニル共重合体膜への硝酸イソソルビドの収着

エチレン・酢酸ビニル共重合体膜への硝酸イソソルビドの収着

Sustained transdermal delivery of zidovudine via controlled release of penetration enhancer

Abstract In vitro permeation of zidovudine (azidothymidine, AZT), a potent antiviral agent acting on acquired immunodeficiency syndrome, through a rat skin from isopropyi myristate (IPM) solution was significantly enhanced by the addition of N -methyl-2-pyrrolidone (MP) as a penetration enhancer. When 50 μl of the IPM solution containing 12 mg/ml of AZT and 20% of MP was applied on rat abdominal skin, about 1 μM of the plasma concentration of AZT was observed at 1–2 h after the application, though the concentration decreased rapidly and was undetectable at 6 h. Though 34% of the applied AZT remained in the IPM solution on the rat skin at 10 h, MP was not detected. In order to maintain a constant level of MP in the solution, ethylene-vinyl acetate copolymer membrane was used for its controlled release in the transdermal delivery system of AZT. A considerable plasma concentration of AZT could be maintained for 10 h after application of this MP release-controlled transdermal system.

Membrane permeation-controlled transdermal delivery system design. Influence of controlling membrane and adhesive on skin permeation of isosorbide dinitrate.

A membrane permeation-controlled transdermal delivery system (MC-TDS) of isosorbide dinitrate (ISDN), a model drug, was prepared from polyvinyl alcohol aqueous gel containing the drug, a membrane consisting of ethylene-vinyl acetate copolymer membrane and acrylic adhesive (EV-a). The permeability of ISDN through the EV-a membrane was 2.5 times higher than that through excised hairless rat skin. The ratio of plasma concentration of ISDN after application of MC-TDS on stripped (damaged) skin relative to intact skin was lower than that after application of Frandol tape-S, a marketed ISDN TDS, which suggests that the EV-a membrane might work as a control membrane for overall delivery rate of ISDN to the body. When MC-TDS stored at 30 degrees C for 13.5-48h was applied to the damaged skin, however, the initial plasma concentration of ISDN was very much higher than the expected therapeutic level and was not controlled by the EV-a membrane. The initial high plasma concentration of ISDN after application of the stored MC-TDS on the damaged skin was due to migration of ISDN from the reservoir to the adhesive during storage at 30 degrees C. The migration of drugs into the adhesive might be an important problem in developing efficient MC-TDS.

Diffusion of a nonionic surfactant through polymeric nonporous and porous membranes

In this work some characteristics of diffusion of a nonionic surfactant, Nonoxynol-9 (N-9, used as a spermicide) through a variety of biocompatible membranes, both nonporous (ethylene-vinyl acetate copolymer membrane) and porous (Celgard 2500 polypropylene film and Mitex filter), are studied. The experiments are conducted in a standard glass diffusion cell, the two chambers of which, i.e., “reservoir” and “sink,” are separated by the interposed membrane. The nonporous membrane is found to be impermeable to the surfactant micelle. The diffusion coefficient of the surfactant in this membrane, obtained from the observed “lag time,” therefore, corresponds to that of the nonaggregated molecule (the “monomer”). An increase in the vinyl-acetate content of the membrane results in a higher diffusivity. The experiments with porous membranes are of two basic types. In type I experiments, the initial reservoir concentration of N-9 is slightly below the CMC while in type II experiments it is above CMC, the initial sink concentration (i.e., that on the other side of the membrane) being zero for both. In the former, the only species diffusing is the monomer. However, in the latter type of experiment two stages of transport are observed, and in the second stage only micellar diffusion takes place. The permeability of the porous membranes to the monomer and the micelle are extracted separately from these two types of experiment. The following observations are made on micellar permeability: (i) it is independent of the surfactant concentration, (ii) it increases by 20%, against a predicted value of 30% (by Stokes-Einstein equation) for a change of temperature from 23 to 37°C, and (iii) its value for the Celgard membrane (pore size = 400 Å) is about 0.53 times that of the Mitex filter (pore size = 10 5Å, the micelle diameter being about 100 Å). The permeability to the monomer, whose size is small (∼50 Å) compared to the membrane pore sizes, is consistent with the value of the free diffusion coefficient reported for a similar surfactant.

ALKALI SAPONIFICATION REACTION OF CELLULOSE TRIACETATE MEMBRANE IN HETEROGENEOUS SYSTEM AND PERVAPORATION WITH THE REACTION

In heterogeneous system, the alkali saponification reaction of cellulose triacetate (CTA) membrane in the mixture of ethanol and water advanced with sharp moving boundary of reacted layer with a linear relationship of the thickness with the reaction time as in the case of ethylene-vinyl acetate copolymer membrane. Sorption and diffusion of H2O and C2 H5 OH under the pervaporation with the reaction were examined, and results were obtained as follows. Experimental values of permeation rates of H2O and C2H5OH through a partially saponified membrane agreed with those calculated by assuming the membrane to be a lamination of two layers of cellulose and CTA. For the pervaporation with the reaction, an equation was obtained. Where F is over all permeation rates for water or ethanol, k is the moving rate of the boundary front, l is the membrane thickness before the reaction and Pcell and PCTA are permeability constants for cellulose and CTA membrane, respectively. Plots of 1/F vs. t showed linear relationships for ethanol and water, respectively. From the results, the permeation constants for H2O and C2H5OH under the heterogeneous reaction were obtained. Diffusivity of alkali ion in the cellulose membrane was found 120 times larger than that in CTA membrane. Summarizing these results, it was concluded that the alkali saponification reaction under pervaporation advanced with a controlling step of boundary reaction. An analogy may be found between the reaction and the Case II type diffusion.

The permeation of benzodiazepines through synthetic membranes.

The permeation of chlordiazepoxide, diazepam, oxazepam, lorazepam, nitrazepam, and nimetazepam through a dimethylpolysiloxane membrane and that of chlordiazepoxide, oxazepam, and nitrazepam through an ethylene-vinyl acetate copolymer membrane were investigated using a newly designed permeation cell. Large permeability values of diazepam and nimetazepam were attributed to their large partition coefficients. Large lag time values of chlordiazepoxide, oxazepam, and nitrazepam through the silicone membrane were rationalized by adsorption of these drugs on silica filler within the silicone membrane. Thus permeation data of these drugs can be interpreted on the basis of their physical properties.

Analysis of permeation profiles of drugs from systems containing micelles.

A theoretical model is introduced to describe the permeation of drug through membranes from systems containing micelles. Taking distribution of drug between aqueous and micellar phases into account, an equation is derived which describes the permeation profile of drug from the system. Applicability of the model was experimentally tested employing local anesthetics, one of five surfactants, and silicone or ethylene-vinyl acetate copolymer membrane.