Ethylene Vinyl Acetate Membranes Research Articles

FTIR imaging for the characterization of controlled-release drug delivery applications.

The diffusion of nicotine in ethanol/water mixtures into an ethylene-vinyl acetate (EVA) copolymer membrane was studied by FTIR imaging. The spatial and temporal distribution of each component in the EVA membrane was demonstrated in the FTIR images. The concentration profiles extracted from these images showed that segregation occurs during diffusion. Nicotine diffuses into EVA ahead of the solvent for 0-60 wt% ethanol/water mixtures, but the segregation behavior changes as the ethanol in the solvent increases to 80 wt%; for the 80 wt% ethanol solvent, D(2)O leads the diffusion front, and for the 100% ethanol solvent, ethanol diffuses into EVA first. The initial swelling rates were calculated from the concentration profiles, and an exponential trend with increasing ethanol in the solvent was observed. The concentration profiles were also used to calculate average diffusion coefficients for the overall solutions and specifically for nicotine. The relative intensities of the aromatic ring stretching bands of nicotine in solution indicate that the solvation properties in pure ethanol and water are not equivalent; a pseudo-conjugation scheme between water and nicotine was proposed to account for this difference. Examination of the intensity of the carbonyl band of the EVA film revealed an interaction with the solvents by hydrogen bonding.

Controlled release of triprolidine using ethylene-vinyl acetate membrane and matrix systems

The studies on the permeability of triprolidine through ethylene-vinyl acetate (EVA) copolymer membrane using two-chamber diffusion cell was carried out to develop the controlled delivery system. To evaluate the effect of drug concentration in reservoir, polyethylene glycol (PEG) 400 was added to saline solution as a solubilizer and a sink condition was maintained in the receptor solution. The permeation rate of drug through EVA membrane was proportional to PEG 400 volume fraction. A linear relationship existed between the permeation rate and the reciprocal of the membrane thickness. Triprolidine-containing matrix was fabricated with EVA copolymer to control the release of the drug. The plasticizers was added for preparing the pore structure of EVA membranes to increase the drug release. The effects of PEG 400, vinyl acetate (VA) contents of EVA, membrane thickness, drug concentration, temperature, and plasticizers, on drug release were studied. The release rate of drug from the EVA matrix increased with PEG 400 volume fraction, increased temperature and drug loading doses. An increased vinyl acetate comonomer content in EVA membrane increased the drug release rate and permeability coefficient. Among the plasticizers used such as alkyl citrates and phthalates, tetra ethyl citrate showed the best enhancing effects showing the enhancement factor of 1.88. The release of triprolidine 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 triprolidine could be achieved using the EVA polymer including the plasticizer.

Formulation of a reservoir-type testosterone transdermal delivery system

A reservoir-type transdermal delivery system of testosterone (TS) was developed using an ethanol/water (70:30) cosolvent system as the vehicle. The maximum permeation rate achieved by 70% (v/v) of ethanol was further increased from 2.69 to 47.83 μg/cm 2/h with the addition of 1.0% dodecylamine as the skin permeation enhancer. The permeation rate of TS through the ethylene vinyl acetate (EVA) membrane was observed to increase as the vinyl acetate content in the copolymer increased. Addition of 1.0% (w/w) gelling agent, hydroxypropyl methlycellulose (HPMC), in the reservoir formulation resulted in desirable rheological properties with an insignificant effect on the skin permeation rate of TS. Thus, a new transdermal delivery system for TS was formulated using EVA membrane coated with a pressure-sensitive adhesive (Duro-Tak 87-2510) and HPMC as a gelling agent. This experimental patch showed comparable plasma concentration profiles in the in vivo study when compared with a commercial product, Androderm®. Moreover, the results suggested the possibility of further enhancing the permeation rate of TS by controlling the composition of the reservoir formulation.

Potentiometric biosensor for l-ascorbic acid based on ascorbate oxidase of natural source immobilized on ethylene–vinylacetate membrane

The development of a potentiometric biosensor for l-ascorbic acid based on ascorbate oxidase is described. The enzyme was extracted of the epicarp of Cucumis sativus L. fruit and immobilized in a graphite/epoxy electrode by occlusion in a poly(ethylene-co-vinyl acetate) matrix (EVA 40% m/m). The electrode showed a sub-Nerntian response (slope of 50.3±0.6 mV), between 8.0×10 −6 and 4.5×10 −4 mol l −1 for ascorbate, when 0.1 mol l −1 KH 2PO 4 buffer at pH 5.0 and 25.0°C was employed. The biosensor was continuously tested, during 15 days (about 300 analyses), and no decrease in the response was observed, for vitamin C determination in pharmaceuticals samples, without any previous treatment. The biosensor was stable for at least 1 month when stored in a refrigerator. The relative standard deviation was about 4% compared to the spectrophotometric method. The response time was about 5 min at room temperature.

Percutaneous absorption and model membrane variations of melatonin in aqueous-based propylene glycol and 2-hydroxypropyl-beta-cyclodextrin vehicles.

Percutaneous absorption and model membrane variations of melatonin (MT) in aqueous-based propylene glycol and 2-hydroxypropyl-beta-cyclodextrin vehicles were investigated. The excised hairless mouse skin (HMS) and two synthetic ethylene vinyl acetate (EVA) and microporous polyethylene (MPE) were selected as a model membrane. The solubility of MT was determined by phase equilibrium study. The vertical Franz type cell was used for diffusion study. The concentration of MT was determined using reverse phase HPLC system. The MT solubility was the highest in a mixture of PG and 2-HP beta CD. The percutaneous absorption of MT through excised HMS increased as the solubility increased. However, the permeability coefficient decreased and then slightly increased in a mixture of PG and 2-HP beta CD. On the other hand, both flux and permeability coefficient through EVA membrane decreased as the solubility increased. No MT was detected over 12 h after starting diffusion through MPE membrane. The flux of MT was dependent on the type of membrane selected. Flux of MT was greatest in excised HMS followed by EVA and MPE membrane. Flux of MT through EVA membrane was 5-20 times lower when compared to excised HMS. Interestingly, volumes of donor phase when MPE membrane was used, significantly increased during the study period. The HMS might be applicable to expect plasma concentration of MT in human subjects based on flux and pharmacokinetic parameters as studied previously. The current studies may be applied to deliver MT transdermally using aqueous-based vehicles and to fabricate MT dosage forms.

Acetylsalicylic acid determination in pharmaceutical samples by FIA-potentiometry using a salicylate-sensitive tubular electrode with an ethylene-vinyl acetate membrane

The construction of a salicylate-sensitive tubular potentiometric electrode for flow injection analysis (FIA) is described, in which an ethylene-vinyl acetate (EVA) copolymeric membrane, 40% in vinyl acetate, is applied directly onto a conducting support consisting of a mixture of an epoxy resin and graphite. The tubular salicylate ion-selective electrode is based on tricaprylyl-trimethyl-ammonium (Aliquat™) salicylate as the ion-exchanger, supported on the polymeric matrix without plasticizer solvent. The tubular electrode showed a response of 58.3 mV per concentration decade within the 5.0×10 −3–5.0×10 −1 mol l −1 salicylate range in 0.1 mol l −1 Tris–HCl buffer (pH=7.5). Iodide is the main analytical interferent; the electrode response time was 5 s at 25°C. Determinations of acetylsalicylic acid in tablet samples by the proposed method exhibit relative errors lower than 2%, when compared with a spectrophotometric method. The useful lifetime of the tubular sensor is longer than 3 months.

Controlled release of ethinylestradiol from ethylene-vinyl acetate membrane

The studies on the permeability of ethinylestradiol (EE) through ethylene-vinyl acetate (EVA) copolymer membrane using a two-chambered diffusion cell were carried out to develop the membrane controlled transdermal delivery system. To evaluate the effect of drug concentration in reservoir, polyethylene glycol (PEG) 400 was added to saline solution as a solubilizer and a sink condition was maintained in the receptor solution. An increased vinyl acetate comonomer content in the EVA membrane increased the drug release rate and permeability coefficient. A linear relationship existed between the permeation rate and the reciprocal of the membrane thickness. Ethinylestradiol-containing matrix was fabricated with EVA copolymer to control the release of the drug. The release of EE from EVA matrix follows a diffusion controlled model, where the quantity released per unit area is proportional to the square root of time. The release rate of drug from EVA matrix increased with PEG 400 volume fraction, temperature and loading dose.

Development of a Transdermal Delivery Device for Melatonin In Vitro Study

AbstractThe present study was undertaken to develop a transdermal delivery device for melatonin and to determine the effects of system design on the release of melatonin. Melatonin(MT) diffusion characteristics from 2 solvents through a series of ethylene vinyl acetate membranes with 4.5%, 9%, 19%, 28% vinyl acetate were characterized using vertical Franz® diffusion cells. The solvent used were 40% (v/v) propylene glycol (PG) and 40%(v/v) propylene glycol with 30%(w/v) 2-hydroxypropyl-β-cytrodextrin. The best release rate (Jss = 0.795 μg/h/cm2) was obtained from the 40% PG vehicle through the 28% vinyl acetate membrane. Melatonin diffusion through this membrane with an acrylate pressure sensitive adhesive (PSA) with and without MT loading was also studied. The data revealed an interaction between MT and the PSA in the systems with MT-loaded adhesive. A MT transdermal delivery device was constructed based on the above data. Effect of storage time (1 day, 2 days, and 3 days) on the developed device was also...

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.

Transdermal Delivery of Propranolol

Three transdermal formulations containing propranolol hydrochloride in a hydrophilic polymer matrix were prepared-one without a rate controlling membrane(H-1), one with a 20μ thick Ethylene Vinyl Acetate(EVA) rate controlling membrane (H-2) and one with a 65μ thick EVA membrane. These patches were evaluated for their in-vitro performance. Cumulative % permeated across excised hairfree rat skin were 79.2% from H-1, 65.53% from H-2 and 53.44% from H-3. Increase in thickness of EVA lead to greater retention of drug in device and a zero order profile was seen with patches H-2 & H-3. Matrix diffusion profile was observed with H-1 patch.

Mechanism of Diffusion of Monosubstituted Benzoic Acids through Ethylene-Vinyl Acetate Copolymers

Ethylene-vinyl acetate (EVAc), a biocompatible copolymer, has been employed as the rate-controlling membrane in several drug delivery systems. To study the mechanism(s) of diffusion of drugs through EVAc membranes, the diffusion, permeability, and partition coefficients of monosubstituted benzoic acids were studied as a function of vinyl acetate content. The diffusion coefficients were found to occupy a narrow range, but the permeability and partition coefficients were found to increase in a nonlinear fashion as a function of vinyl acetate content, indicating that the diffusion process was partition governed. The partitioning data were analyzed on the basis of the partitioning between the vinyl acetate moiety and the aqueous phase, assuming the formation of 1:1 benzoic acid:vinyl acetate complexes. The effects of ionization and the addition of 2-propanol to the diffusion medium were studied. The results suggest that the un-ionized neutral forms of the benzoic acids are responsible for transport across the copolymer. Altering the composition of the medium by addition of 2-propanol increased the donor phase solubility of the acid, the steady-state rate, and the permeability, suggesting that cosolvent modification provides an excellent chemical means to increase release rates.

In vitro percutaneous transport of sodium diclofenac and diclofenac from oleaginous vehicle.

The penetration enhancement of sodium diclofenac and diclofenac by alcohols with various alkyl chains (C8 to C14) was evaluated by the steady state flux of diclofenac through rat abdominal skin. Decanol showed the greatest effect in this series. A more remarkable enhancing effect of the alcohols was observed in sodium diclofenac than in diclofenac. Diclofenac can penetrate through the ethylene-vinyl acetate membrane as a lipoid model membrane, but sodium diclofenac can not. Decanol enhanced the penetration of phenol red being dependent on its concentration in the vehicle. Therefore, decanol may interact with lipoid components of the skin and increase the aqueous pathway in the skin. These results indicate that sodium diclofenac and diclofenac may be penetrated through partially different pathways.

Transdermal Delivery of Levonorgestrel IV: Evaluation of Membranes

A series of experiments were performed to evaluate the flux of levonorgestrel (LN), ethyl acetate (EtAc), and ethanol (EtOH) through excised rat skin, through a variety of synthetic membranes and through membranes supported on rat skin. Using a donor phase of EtAc:EtOH (7:3) containing excess solid LN, the flux of LN through rat skin was approximately 1.0 microgramc/cm2.h. The normalized fluxes of LN, EtAc, and EtOH through ethylene vinyl acetate (EVAc) copolymers of varying vinyl acetate (VAc) content (12 to 25%) were 1.3 to 3.1 x 10(-8), 2.6 to 6.8 x 10(-4), and 4.8 to 9.9 x 10(-5) g.cm/cm2.h, respectively. Permeability experiments were also performed with the EVAc membranes supported on rat skin. By selecting the VAc content and thickness of the EVAc membranes, it was possible to control the delivery of enhancer (EtAc:EtOH) through rat skin (membrane-rate control) or to let the skin control the overall delivery of enhancer.

Ethanok:Water Mutually Enhanced Transdermal Therapeutic System I: Nitroglycerin Solution Properties and Membrane Transport

The solution properties of aqueous ethanol donor solutions were characterized for the particular case of an increased flux nitroglycerin transdermal system. Permeation through porous and nonporous polymer membranes was investigated and modelled. While the permeation of ethanol through the porous membranes is adequately described by theory, clogging of pores occurs in the presence of lactose. Permeation through ethylene vinyl acetate membranes reflects interactions of the solute and solvent with the polymer.

Enhancement of transdermal delivery by superfluous thermodynamic potential. I. Thermodynamic analysis of nifedipine transport across the lipoidal barrier.

In vitro techniques were used to test certain concepts regarding the enhancement of the transdermal delivery of nifedipine from topical vehicles. Tested vehicles include the volatile solvent acetone, nonvolatile solvents such as propylene glycol and isopropyl myristate, volatile/nonvolatile mixtures, and those mixtures with a polymer additive. An ethylene-vinyl acetate (EVA) copolymer membrane was used as the lipoidal barrier for the diffusing drug. Not merely the rate of transport per unit area, but the activity coefficient and the diffusion coefficient of the penetrating agent in the barrier were obtained. Despite the 10,000-fold difference in the vehicle concentration, water and several hydrophilic vehicles containing finely ground suspensions of the drug produced nearly the same rate of penetration. Some lipophilic solvents affected the barrier function of the EVA membrane to promote penetration of the drug. It has been found that the activity coefficient in the EVA membrane is very susceptible to wide variations by imbibition of such solvents. From volatile/nonvolatile mixtures, a transient enhancement in the transport of nifedipine across the membrane was observed. The increase in the flux was accounted for by the increase in the thermodynamic activity of the drug in the nonvolatile vehicle caused by the evaporation of the volatile component. The eventual decrease in penetration was the result of the drug precipitation from the supersaturated solution. The precipitation was inhibited and/or retarded during the entire time course of the experiments when a polymer additive was present. The steady-state fluxes from mixtures with a polymer additive were higher by about 3 to 5 times than that of the control experiment.

Mechanism of diffusion of compounds through ethylene vinyl acetate copolymers I. Kinetics of diffusion of l-chloro-4-nitrobenzene, 3,4-dimethylphenol and 4-hexylresorcinol

The mechanism of diffusion of drugs through ethylene-vinyl acetate (EVA) copolymers has been studied. The observed permeability coefficients for the phenols, 4-hexylresorcinol and 3,4-dimethylphenol, increase in a non-linear fashion with increasing vinyl acetate content in the copolymer. Furthermore, their partition coefficients vary in a non-linear manner with increasing vinyl acetate content, while the partition coefficient of a non-phenolic compound, 1-chloro-4-nitrobenzene, increases in a linear manner. Since the diffusion coefficients for the two phenols are shown to be independent of vinyl acetate content, the permeability of phenols in EVA membranes depends almost entirely on the partition coefficient. The non-linear partitioning behavior of the phenolic compounds can be attributed to the formation of vinyl acetate-phenol complexes. The linear increase in partition coefficient for 1-chloro-4-nitrobenzene is attributed to a straightforward solubility enhancement.