Ethylene Vinyl Acetate Membranes Research Articles

Expression Microdissection for the Analysis of miRNA in a Single-Cell Type

Cell-specific microRNA (miRNA) expression estimates are important in characterizing the localization of miRNA signaling within tissues. Much of these data are obtained from cultured cells, a process known to significantly alter miRNA expression levels. Thus, our knowledge of in vivo cell miRNA expression estimates is poor. We previously demonstrated expression microdissection-miRNA-sequencing (xMD-miRNA-seq) to acquire in vivo estimates, directly from formalin-fixed tissues, albeit with a limited yield. In this study, we optimized each step of the xMD process, including tissue retrieval, tissue transfer, film preparation, and RNA isolation, to increase RNA yields and ultimately show strong enrichment for in vivo miRNA expression by qPCR array. These method improvements, such as the development of a noncrosslinked ethylene vinyl acetate membrane, resulted in a 23- to 45-fold increase in miRNA yield, depending on the cell type. By qPCR, miR-200a increased by 14-fold in xMD-derived small intestine epithelial cells, with a concurrent 336-fold reduction in miR-143 relative to the matched nondissected duodenal tissue. xMD is now an optimized method to obtain robust in vivo miRNA expression estimates from cells. xMD will allow formalin-fixed tissues from surgical pathology archives to make theragnostic biomarker discoveries.

Never boring: Non-invasive palaeoproteomics of mummified human skin

The scientific analysis of mummified individuals can reveal important details on the way people lived and died in the past. Palaeoproteomic approaches are theoretically suitable for obtaining information on the extent of tissue preservation, on the use of protein-based substances for embalming and/or restoration, as well as for characterising the microbiota from both the individual and the environment. However, these analyses usually require the destruction of a sample of tissue, a practice which is (obviously) discouraged by most museums. Unfortunately, this means that in-depth studies, for example by taking multiple samples from each individual, are seldom feasible. Here we show that a non-invasive sampling technique, based on mixed-bed chromatographic media embedded on ethylene vinyl acetate membranes (EVA), which had previously been used exclusively on historical material, was successful in extracting ancient proteins from the surface of Egyptian mummies. We tested the method on a decontextualised fragment of skin and assessed the endogeneity of its metaproteome by comparison with a procedural blank. Furthermore, we retrieved and authenticated sequences of human collagen and keratin, as well as potential bacterial/fungal biodeteriogens, from the mummy of a young woman (Supp. 16747 of the Museum of Anthropology and Ethnography of the University of Turin) who lived and died during the Old Kingdom of Egypt.

Synergistic Tandem Solar Electricity-Water Generators

Summary Energy and clean water are two intertwined fundamental elements for human civilization and sustainable development. Here, we devise a monolithic tandem solar electricity-water generator that synergistically produces electricity and clean water by utilizing the full spectrum of solar irradiance. The tandem generator has two components: a top infrared-transparent photovoltaic device using above-band-gap photons, and a bottom solar water purifier using the below-band-gap photons. More strikingly, a well-designed water-proof thermal interconnecting layer (WTIL) makes these two components work synergistically: the bottom purifier serves as an evaporative cooler of the top solar cell to increase its efficiency, whereas the thermalization energy of the top cell is reutilized by the bottom purifier for producing more clean water. We experimentally demonstrate that a prototype hybrid tandem solar device with WTIL can generate electricity with a power output of 204 W m−2 and purify water at a rate of 0.80 kg m−2 h−1 under 1-sun illumination.

Surface roughness of different contraceptive vaginal rings: evaluation by scanning electron microscope (SEM)

Objective: The aim of the study was to evaluate whether the compositions of the ethylene vinyl acetate (EVA) membrane of two different contraceptive vaginal rings could influence the surface roughness, which is associated with the possible accumulation of vaginal biomass on the rings during use.Methods: We measured and compared the surface roughness of unused vaginal rings, NuvaRing and Ornibel, using a scanning electron microscope (SEM) and dedicated software that can convert SEM images into 3D models. Average roughness (Ra), average quadratic roughness (Rq) and mean height of the irregularities at 10 points (Rz) were calculated.Results: Different thicknesses of the EVA membranes between the two rings were noted. No significant differences were found between the two rings in the three evaluated values of surface roughness (NuvaRing vs Ornibel, respectively: Ra, 1.53 ± 0.14 vs 1.61 ± 0.14 µm, p = 0.141; Rq, 2.03 ± 0.25 vs 2.07 ± 0.16 µm, p = 0.688; Rz, 11.4 ± 3.1 vs 11.4 ± 2.4 µm, p = 0.987).Conclusion: The different composition of the vaginal rings’ EVA membrane is not associated with different surface roughness. Ornibel is equivalent to NuvaRing in terms of surface roughness, despite the different composition of the membrane polymers.

Surface modification of ethylene-vinyl acetate membrane grafted with poly(N-isopropylacrylamide) by UV-irradiation

Surface modification of ethylene-vinyl acetate membrane by grafting poly(N-isopropylacrylamide) was initiated under UV-irradiation. Besides benzophenone and ammonium persulfate were used as initiators, which could enhance the yield of grafting markedly. The occurrence of grafting polymerization of N-isopropylacrylamide was testified by the attenuated total multiple reflection technique and X-ray photoelectron spectroscopy. Scanning electron micrograph showed that the surface morphology of ethylene-vinyl acetate membrane changed after modification. The lower critical solution temperature of the membrane was determined by differential scanning calorimetry. The wettability of membrane was investigated by water contact angle measurement. The results showed that the grafting degree increased with irradiation time, monomer and ammonium persulfate concentration at the beginning of reaction. It was also found that the modified membrane surface became hydrophilic and displayed thermosensitivity similar to that of poly(N-isopropylacrylamide) gel, and the lower critical solution temperature was about 32°C.

Radon diffusion coefficients in 360 waterproof materials of different chemical composition

This paper summarises the results of radon diffusion coefficient measurements in 360 common waterproof materials available throughout Europe. The materials were grouped into 26 categories according to their chemical composition. It was found that the diffusion coefficients of materials used for protecting houses against radon vary within eight orders from 10(-15) to 10(-8) m(2) s(-1). The lowest values were obtained for bitumen membranes with an Al carrier film and for ethylene vinyl acetate membranes. The highest radon diffusion coefficient values were discovered for sodium bentonite membranes, rubber membranes made of ethylene propylene diene monomer and polymer cement coatings. The radon diffusion coefficients for waterproofings widely used for protecting houses, i.e. flexible polyvinyl chloride, high-, low-density polyethylene, polypropylene and bitumen membranes, vary in the range from 3 × 10(-12) to 3 × 10(-11) m(2) s(-1). Tests were performed which confirmed that the radon diffusion coefficient is also an effective tool for verifying the air-tightness of joints.

Transdermal delivery of fentanyl from matrix and reservoir systems: Effect of heat and compromised skin

The United States Food and Drug Administration (FDA) has received numerous reports of serious adverse events, including death, in patients using fentanyl transdermal systems (FTS). To gain a better understanding of these problems, the current research focuses on the in vitro characterization of fentanyl reservoir (Duragesic®) and matrix (Mylan) systems with respect to drug release and skin permeation under conditions of elevated temperature and compromised skin. In addition, different synthetic membrane barriers were evaluated to identify the one that best simulates fentanyl skin transport, and thus may be useful as a model for these systems in future studies. The results indicate that reservoir and matrix FTS are comparable when applied to intact skin at normal skin temperature but the kinetics of drug delivery are different in the two systems. At 40°C, the permeation rate of fentanyl was twice that seen at 32°C over the first 24 h in both systems; however, the total drug permeation in 72 h is significantly higher in the reservoir FTS. When applied to partially compromised skin, matrix FTS has a greater permeation enhancement effect than reservoir FTS. The intrinsic rate limiting membrane of the reservoir system served to limit drug permeation when the skin (barrier) permeability was compromised. Different ethylene vinyl acetate membranes were shown to have fentanyl permeability values encompassing the variability in human skin. Results using the in vitro model developed using synthetic membranes suggest that they mimic the effect of compromised skin on fentanyl permeability. Especially for highly potent drugs such as fentanyl, it is important that patients follow instructions regarding application of heat and use of the product on compromised skin. © 2009 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 99: 2357–2366, 2010

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.

Timely drug delivery from controlled-release devices: Dynamic analysis and novel design concepts

Design tools are provided to assist in the development of drug-release devices that can control the time to establish a steady-state flux in addition to a desired delivery rate. In this contribution, the primary focus is placed on passive, heat-aided, and electrically assisted transport through planar membranes. Approximate analytical methods, that describe process dynamics, were applied to appropriate mathematical models to derive relationships between the system properties (e.g., diffusion coefficient, temperature and voltage potential) and the flux response time. Three case studies were investigated to illustrate the theoretical results. A steady-state benzocaine flux through ethylene-vinyl acetate membranes was achieved in 40 min as predicted by a first-moment time constant approach. It took 5 h and 45 min to reach a constant delivery rate of amitriptyline HCl across human skin for a donor cell concentration of 0.032 M and an electric current of 0.4 mA/cm 2. Based on the upper limit and range estimates of the first eigenvalue, the onset of steady-state flux occurred between 3.4 and 3.5 min when the donor and receiver cells were maintained at 47 and 37 °C, respectively. These predictions were confirmed by simulation, experimental evidence and graphical examination of drug-release data.

Study of gas separation properties of ethylene vinyl acetate (EVA) copolymer membranes prepared via phase inversion method

The gas separation properties of ethylene vinyl acetate (EVA) membranes containing 18 and 28 wt% of vinyl acetate (VA) were investigated in this study. The effects of membrane preparation conditions, such as thermal and thermal/wet phase inversion, and the type of solvent on the gas separation properties of EVA membranes were investigated. The permeation of pure O 2, N 2, CH 4, and CO 2 gases at different feed pressures ranging from 2 to 11 bar were examined. The results indicated that the CO 2 permeability was evidently higher than those of the other gases. Furthermore, the solubility mechanism was found to be the dominant mechanism for permeation of gases through EVA membranes. Moreover, the membranes prepared using tetrahydrofuran (THF) as solvent showed higher gas permeabilities than those prepared using chloroform (CHCl 3) as solvent. The results indicated that the gas permeabilities through membranes prepared using wet phase inversion technique were higher. Also, the membranes prepared by thermal/wet phase inversion method at higher temperatures showed improved gas separation properties. In addition, the membrane with higher VA content prepared using THF as solvent presents higher gas separation properties. Trade-off evaluation also showed that certain types of the prepared EVA membranes in this study have potential for commercialization.

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.

Effect of formation conditions of poly(ethylene- co-vinyl acetate) membrane on the membrane physical structure and pervaporation properties in the recovery of ethyl acetate from aqueous solution

The solution properties, intrinsic viscosity [ η] and Huggins constant K H of ethylene-vinyl acetate (EVA) copolymer with 38 wt% vinyl acetate content (EVA38) in solvents of chloroform (CF), 1,2-dichloroethane (DCE) and cyclohexane (CYH) were measured by an Ubbelohode viscometer. The physical structure and pervaporation performances of the EVA membranes cast from different solvents were also investigated by wide-angle X-ray diffraction (WAXD), contact angle, etc. The EVA38 in non-selective solvent CF reveals high [ η] and low K H, both chain segments of vinyl acetate and ethylene are expanded in the solutions, and homogeneous distribution in the EVA38 membranes. It results in high pervaporation performance of both separation factor and permeation flux in the recovery of ethyl acetate from aqueous solutions. Oppositely, EVA38 membranes from selective solvents DCE and CYH give low pervaporation performance relatively due to chains aggregation of ethylene segments or vinyl acetate segments in EVA38. The differences of the pervaporation performance and physical structure of EVA38 membranes from different solvents weaken gradually and disappeared finally with increasing the intensity of post-treatment.

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.

Transdermal Delivery of Flurbiprofen: Permeation Enhancement, Design, Pharmacokinetic, and Pharmacodynamic Studies in Albino Rats

The enhancing effects of lemon oil on the transdermal penetration of flurbiprofen through rat skin invitro and in vivo was investigated. The maximum flux achieved by Isopropyl alcohol (IPA):Propylene glycol (PG) (70:30% v/v) solvent mixture was further increased by lemon oil. The flux of flurbiprofen through ethylene vinyl acetate microporous membrane was evaluated. The membrane altered the flux of flurbiprofen significantly. The reservoir type of transdermal patch was fabricated using flurbiprofen viscous system, ethylene vinyl acetate membrane, and backing film. Histological investigations were done on rat skin samples treated with solvent systems with or without penetration enhancer for 24 hr. No skin irritation was seen. Lemon oil produced more pronounced change in stratum corneum and the epidermis as compared with the control groups.The pharmacokinetics of flurbiprofen in albino rats following application of a transdermal patch for 24 hr was evaluated. The maximum plasma concentration (Cmax) and AUC0–α of the patch formulation was 1.7 and 1.6 times, increased respectively as compared with the control patch formulation. Quantity of the drug accumulated in the excised skin to which test patch formulation was applied was more than the one to which control patch formulation was applied.Anti-inflammatory effect in the Carrageenin-induced paw edema in rat was significantly higher than the control patch formulation.

In Vitro and in Vivo Characterization of a Newly Developed Clonidine Transdermal Patch for Treatment of Attention Deficit Hyperactivity Disorder in Children

The aim of this study was to characterize a newly developed clonidine transdermal patch, KBD-transdermal therapeutic system (TTS), for the treatment of attention deficit hyperactivity disorder in children. In vitro release, penetration, and in vivo pharmacokinetics in rabbits were investigated. The smaller size of KBD-TTS (2.5 mg/2.5 cm2) showed a similar in vitro penetration to those of Catapres-TTS (2.5 mg/3.5 cm2, a clonidine transdermal patch used for the treatment of hypertension, Alza Corporation, U.S.A.). The transdermal penetration rate of clonidine was mainly controlled by the ethylene vinylacetate membrane used in the patch. The skin layer may be only a minor rate-limiting barrier after the topical skin layer at the dosing site is saturated with penetrating clonidine in the initial phase (0 to 12 h). A sensitive liquid chromatography-mass spectrometry method for the quantification of clonidine in rabbit plasma was developed using solid-phase extraction and gradient elution on LC combined with the selected-ion monitoring (SIM) mode. A single dose of clonidine transdermal patch (KBD-TTS) or Catapres-TTS was transdermally administered to rabbits (n=6 each) and removed after 168 h. The average half-life, Tmax, Cmax and Css values of clonidine in rabbits following administration of KBD-TTS were 19.27+/-4.68 h, 52.56+/-25.77 h, 27.39+/-9.03 ng/ml, and 25.82+/-9.34 ng/ml, similar to those of Catapres-TTS, respectively. The clonidine plasma concentration of KBD-TTS reached a steady state at 24 h through 168 h. The in vitro release rate of the clonidine from KBD-TTS significantly correlated with the in vivo absorption rate (p<0.001).

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.

Feasibility of drug delivery to the posterior pole of the rabbit eye with an episcleral implant.

To evaluate the feasibility of a nonbiodegradable polymeric episcleral implant as a new controlled intraocular delivery system of betamethasone (BM) to the posterior pole of the eye. The episcleral implant, which is composed of a drug-releasing component and a suture tag, released BM through an ethylene vinyl acetate membrane. The implants were placed on the sclera in 12 eyes of 12 Japanese white rabbits so that the drug-releasing surface could attach to the sclera at the posterior pole. BM concentrations in the aqueous humor, vitreous, and retina-choroid (posterior half and anterior half) were determined by high-performance liquid chromatography (HPLC) at weeks 1, 2, and 4 after implantation. In addition, the intraocular tissue distribution of the drug was evaluated by fluorescein microscopy after implantation of the implant loaded with 6-carboxy fluorescein diacetate (6-CFDA) as a drug marker. Retinal toxicity was evaluated by electroretinography and histologic examination. The implant showed zero-order release profiles both in vitro and in vivo for 4 weeks. BM concentrations in the retina-choroid after implantation were maintained above the concentrations effective for suppressing inflammatory reactions for at least 4 weeks. The BM concentration was greater in the posterior half of the retina-choroid than in the vitreous. It was confirmed that 6-CFDA penetrated through the sclera and dispersed into the retina-choroid. Fluorescence from 6-CFDA gradually decreased in intensity with increased distance from the implantation site. Electroretinography and histologic study showed no substantial toxic reactions. These findings suggest that the episcleral implant may be a useful drug carrier for intraocular delivery of BM, especially for the posterior part of the eye.

Formulation and Evaluation of Limonene-Based Membrane-Moderated Transdermal Therapeutic System of Nimodipine

The aim of the present study was to design a membranemoderated transdermal therapeutic system (TTS) of nimodipine using 2% w/w hydroxypropyl methylcellulose (HPMC) gel as a reservoir system containing 4% w/w of limonene as a penetration enhancer. The permeability flux of nimodipine through ethylene vinyl acetate (EVA) copolymer membrane was found to increase with an increase in vinyl acetate content in the copolymer (9 to 28%). The effect of pressure-sensitive adhesives such as TACKWHITE A 4MED® on the permeability of nimodipine through EVA membrane 2825 (28% w/w vinyl acetate) or membrane/rat skin composite also was studied. The permeability flux of nimodipine from the chosen EVA 2825 (with 28% vinyl acetate content) was 159.72 ± 1.96 μg/cm2/hr, and this flux further decreased to 141.85 ± 1.54 μg/cm2/hr on application of pressure-sensitive adhesive (TACKWHITE A 4MED®). However, the transdermal permeability flux of nimodipine across EVA 2825 membrane coated with TACKWHITE A 4MED®/rat skin composite was found to be 126.59 ± 2.72 μg/cm2/hr, which is 1.3-fold greater than the required flux. Thus, a new transdermal therapeutic system for nimodipine was formulated using EVA 2825 membrane coated with a pressure-sensitive adhesive TACKWHITE 4A MED® and 2% w/w HPMC gel as reservoir containing 4% w/w of limonene as a penetration enhancer. The bioavailability studies in healthy human volunteers indicated that the TTS of nimodipine, designed in the present study, provided steady-state plasma concentration of the drug with minimal fluctuations for 20 hr with improved bioavailability in comparison with the immediate release tablet dosage form.

Enhanced transdermal delivery of triprolidine from the ethylene-vinyl acetate matrix

Triprolidine-containing matrix was fabricated with ethylene–vinyl acetate (EVA) copolymer to control the release of the drug. The permeation rate of triprolidine in the stripped skin was greatly larger than that in the whole skin. Thus it showed that the stratum corneum acts as a barrier of skin permeation. The effect of penetration enhancer and stripping of skin on the permeation of triprolidine through the excised mouse skin was studied. Penetrating enhancers showed increased flux probably due to the enhancing effect on the skin barrier, the stratum corneum. Among enhancers used such as glycols, fatty acids and non-ionic surfactants, polyoxyethylene-2-oleyl ether showed the best enhancement. The permeability of triprolidine was markedly increased with stripping of the mouse skin to remove the stratum corneum that acts as a barrier of skin permeation. For the controlling transdermal delivery of triprolidine, the application of EVA membrane containing permeation enhancer could be useful in the development of transdermal drug delivery system.

Influence of limonene on the bioavailability of nicardipine hydrochloride from membrane-moderated transdermal therapeutic systems in human volunteers

The aim of the present study was to develop a membrane-moderated transdermal therapeutic system (TTS) of nicardipine hydrochloride using 2%w/w hydroxy propyl cellulose (HPC) gel as a reservoir system containing 4%w/w of limonene as a penetration enhancer. The permeability flux of nicardipine hydrochloride through ethylene vinyl acetate (EVA) copolymer membrane was found to increase with an increase in vinyl acetate (VA) content in the copolymer. The effect of various pressure-sensitive adhesives (MA-31, MA-38 or TACKWHITE A 4MED) on the permeability of nicardipine hydrochloride through EVA membrane 2825 (28% w/w VA) or membrane/skin composite was also studied. The results showed that nicardipine hydrochloride permeability through EVA 2825 membrane coated with TACKWHITE 4A MED/skin composite was higher than that coated with MA-31or MA-38. Thus a new TTS for nicardipine hydrochloride was formulated using EVA 2825 membrane coated with a pressure-sensitive adhesive TACKWHITE 4A MED and 2%w/w HPC gel as reservoir containing 4%w/w of limonene as a penetration enhancer. The bioavailability studies in healthy human volunteers indicated that the TTS of nicardipine hydrochloride, designed in the present study, provided steady state plasma concentration of the drug with minimal fluctuations for 20 h with improved bioavailability in comparison with the immediate release capsule dosage form.