Ethylene-vinyl Acetate Copolymer Matrix Research Articles

3D Printed Mini-Floating-Polypill for Parkinson's Disease: Combination of Levodopa, Benserazide, and Pramipexole in Various Dosing for Personalized Therapy.

Therapy for Parkinson’s disease is quite challenging. Numerous drugs are available for symptomatic treatment, and levodopa (LD), in combination with a dopa decarboxylase inhibitor (e.g., benserazide (BZ)), has been the drug of choice for years. As the disease progresses, therapy must be supplemented with a dopamine agonist (e.g., pramipexole (PDM)). Side effects increase, as do the required dose and dosing intervals. For these specific requirements of drug therapy, the 3D printing method fused deposition modelling (FDM) was applied in this study for personalized therapy. Hot melt extrusion was utilized to produce two different compositions into filaments: PDM and polyvinyl alcohol for rapid drug release and a fixed combination of LD/BZ (4:1) in an ethylene-vinyl acetate copolymer matrix for prolonged drug release. Since LD is absorbed in the upper gastrointestinal tract, a formulation that floats in gastric fluid was desired to prolong API absorption. Using the FDM 3D printing process, different polypill geometries were printed from both filaments, with variable dosages. Dosage forms with 15–180 mg LD could be printed, showing similar release rates (f2 > 50). In addition, a mini drug delivery dosage form was printed that released 75% LD/BZ within 750 min and could be used as a gastric retentive drug delivery system due to the floating properties of the composition. The floating mini-polypill was designed to accommodate patients’ swallowing difficulties and to allow for individualized dosing with an API release over a longer period of time.

Comparing Multi-Walled Carbon Nanotubes and Halloysite Nanotubes as Reinforcements in EVA Nanocomposites.

The influence of carbon multi-walled nanotubes (MWCNTs) and halloysite nanotubes (HNTs) on the physical, thermal, mechanical, and electrical properties of EVA (ethylene vinyl acetate) copolymer was investigated. EVA-based nanocomposites containing MWCNTs or HNTs, as well as hybrid nanocomposites containing both nanofillers were prepared by melt blending. Scanning electron microcopy (SEM) images revealed the presence of good dispersion of both kinds of nanotubes throughout the EVA matrix. The incorporation of nanotubes into the EVA copolymer matrix did not significantly affect the crystallization behavior of the polymer. The tensile strength of EVA-based nanocomposites increased along with the increasing CNTs (carbon nanotubes) content (increased up to approximately 40% at the loading of 8 wt.%). In turn, HNTs increased to a great extent the strain at break. Mechanical cyclic tensile tests demonstrated that nanocomposites with hybrid reinforcement exhibit interesting strengthening behavior. The synergistic effect of hybrid nanofillers on the modulus at 100% and 200% elongation was visible. Moreover, along with the increase of MWCNTs content in EVA/CNTs nanocomposites, an enhancement in electrical conductivity was observed.

Synergistic effects of two types of ionic liquids on the dispersion of multiwalled carbon nanotubes in ethylene-vinyl acetate elastomer: preparation and characterization of flexible conductive composites

Flexible conductive composites based on an elastomer, ethylene-vinyl acetate copolymer (EVM), and multiwalled carbon nanotubes (MWCNTs) were fabricated by melt-blending and subsequent crosslinking. Two types of ionic liquids, tributylmethylammoniu bis(trifluoromethanesulfonyl)imide and 1-ehtyl-3-methylimidazolium tetrafluoroborate, have been used to modify MWCNTs for the purpose to improve the dispersion of MWCNTs in the polymer matrix. It was found that the MWCNTs modified by the individual IL form agglomerates in the EVM matrix, while the MWCNTs modified by the two types of ILs simultaneously disperse in the EVM matrix homogeneously. Moreover, the nanocomposites based the MWCNTs modified by the combination of the two ILs exhibit improved mechanical and electrical properties. The mechanism of such synergistic effects has been investigated. It was found that EVM is miscible with tributylmethylammoniu bis(trifluoromethanesulfonyl)imide and it is immiscible with 1-ehtyl-3-methylimidazolium tetrafluoroborate. On the other hand, MWCNTs show higher interaction with 1-ehtyl-3-methylimidazolium tetrafluoroborate than tributylmethylammoniu bis(trifluoromethanesulfonyl)imide. Therefore, the uniform dispersion of MWCNTs in EVM matrix is attributed to the “bridging” effects by the two ILs due to the different interactions of the two ILs with MWCNTs and EVM. The application by two types of ILs modified MWCNTs in polymer matrix opens a new fabrication strategy for high performance polymer nanocomposites.

Molecular transport behaviour of organic solvents through halloysite nanotubes filled ethylene–vinyl acetate copolymer

The transport behaviour of three organic solvents (benzene, toluene and xylene) through halloysite nanotubes (HNTs) filled ethylene–vinyl acetate (EVA) copolymer composites have been investigated in the temperature range 303–323 K. The effects of HNTs loading, nature of solvent and temperature on the transport behaviour of solvents through composites were studied. It has been observed that all the systems follow a Fickian mode of transport on increasing temperature. The solvent uptake and sorption coefficient decreases with the increase in halloysite loading while diffusion coefficients and permeation coefficients were found to be dependent on the concentration of filler. The percentage of bounds rubber content and swelling ratio decreases up to 7.5 phr filler content, whereas above 7.5 phr filler loading were found to be increased due to poor dispersion of halloysite in EVA copolymer matrix. The transport behaviour of three organic solvents was further validated by their crosslink density values. The thermodynamic parameters such as enthalpy, entropy and free energy of sorption were evaluated. The positive values of free energy indicate the non-spontaneity of the sorption of HNTs filled EVA in aromatic solvents at 303 K.

Preparation and flame retardancy of a novel flame‐retardant poly(ethylene‐co‐vinyl acetate)/aluminum hydroxide composites containing phosphorus

AbstractA novel flame‐retardant (SPDH) containing phosphorus was synthesized through the reaction of 10‐(2,5‐dihydroxyphenyl)‐9,10‐dihydro‐9‐oxa‐10‐phosphaphenanthrene‐10‐oxide and synthesized intermediate product 3,9‐dichloro‐2,4,8,10‐tetraoxa‐3,9‐diphosphaspiro[5.5] undecane‐3,9‐dioxide, which was used for optimizing the flame retardancy of ethylene‐vinyl acetate copolymer (EVM) rubber/aluminum hydroxide (ATH) composites. The microstructure of SPDH was characterized and determined by Fourier transform infrared and nuclear magnetic resonance spectroscopy. Thermogravimetric analysis (TGA) showed that SPDH had good charring effect at high temperature (600°C). The flame retardancy of the optimized EVM/ATH composites by SPDH was investigated by limiting oxygen index (LOI), cone calorimeter, and UL‐94 vertical burning tests. A higher LOI value (29.8%) and better UL‐94 rating (V‐0) can be achieved for the optimized EVM/ATH composite (EVM‐7) than EVM/ATH composite without SPDH (EVM‐3) with the total loading of additives. The heat release rate decreased and residual mass increased gradually as the loading of SPDH increased for the optimized EVM/ATH composites. There existed distinct synergistic flame‐retardant effect between SPDH and ATH in EVM matrix. POLYM. COMPOS., 2011. © 2011 Society of Plastics Engineers

Study on the flame retardancy of EVM/magnesium hydroxide composites optimized with a flame retardant containing phosphorus and silicon

A novel phosphorus-silicon-containing flame retardant, spirocyclic pentaerythritol bisphosphorate disphosphoryl chloride/9, 10-dihydro-9-oxa-10-phosphaphanthrene-10-oxide/vinyl methyl dimethoxysilane (SPDV), was synthesized successfully and used for optimizing the flame retardancy of ethylene-vinyl acetate copolymer (EVM) rubber/magnesium hydroxide (MDH) composites. The microstructure of SPDV was characterized and determined by Fourier transform infrared (FTIR) and nuclear magnetic resonance (NMR) spectroscopy. Thermogravimetric analysis (TGA) showed that SPDV had good charring effect in air even at high temperature (800°C). The flame retardancy of the optimized EVM/MDH composites by SPDV was investigated by limiting oxygen index (LOI), cone calorimeter, and UL-94 vertical burning tests. A higher LOI value (29.4%) and better UL-94 rating (V-0) can be achieved for the optimized EVM/MDH composite (EVM-7) than EVM/MDH composite without SPDV (EVM-3) with the total loading of additives. The HRR decreased and residual mass increased gradually as the loading of SPDV increased for the optimized EVM/MDH composites. There existed distinct synergistic intumescent flame-retardant effect between SPDV and MDH in EVM matrix. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011

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.

Formulation and Evaluation of Ethylene-Vinyl Acetate Copolymer Matrix Patches Containing Formoterol Fumarate

The skin permeability and stability of formoterol fumarate (FF) in matrix patches containing l-menthol as an enhancer and N-methyl-2-pyrrolidone (NMP) as the solvent were investigated. Using a total of 28 matrix patches having a similar composition, containing ethylene-vinyl acetate (EVA) as the forming polymer and hydrogenated rosin glycerol ester (Ester Gum H) as the adhesive, the skin permeation of FF was found to increase with increasing l-menthol and NMP contents. FF in the matrix patches containing NMP in the range of 4.8-7.2% was stable, but stability decreased at higher values. With a standard matrix patch containing FF, the Cmax and AUC(0-24) values were found to be 1.93 ng/ml after 4 h percutaneous application to rats and 25.6 ng x h/ml. The bioavailability after percutaneous exposure was equivalent to 15.2% of the AUC(0-24) after intravenous administration. Percutaneous application proved efficacious with regard to control of simulated asthma at dose levels lower than those with which side effects occurred. Thus an optimized matrix patch containing FF was prepared with potential advantages for control of asthma.

Characterization of Glucose-Mediated Insulin Release from Implantable Polymers

We characterized a glucose-sensitive, controlled-release insulin delivery system. Insulin release rates increased when glucose was perfused in the release media surrounding the matrix. The system was composed of solid, particulate insulin, incorporated into an ethylene–vinyl acetate copolymer (EVAc) matrix. Feedback control was mediated by the glucose oxidase enzyme immobilized to Sepharose beads, which were incorporated along with insulin into the EVAc matrix. When glucose in solution entered the insulin delivery system, gluconic acid was produced, causing a drop in the microenvironmental pH of the matrix. This fall in pH resulted in a rise in insulin solubility and consequently a rise in the insulin release rate from the matrix. Insulin concentrations increased in vitro and in vivo in response to glucose infusion. The increased insulin release was shown to consist of a finite pulse of insulin that required an optimal recovery period of 1h to achieve a maximal repeated response to a glucose stimulus. Repeated pulses were demonstrated over a 4h period. An optimum enzyme ratio was also determined.

Macromolecules released from polymers: diffusion into unstirred fluids

Polymers that release macromolecules may be useful for preventing and treating human disease. In certain applications of polymeric controlled release, like drug therapy of brain disease and immunoprotection of mucus epithelia, effectiveness may be limited by diffusion through an unstirred fluid near the polymer. Using computer-assisted epifluorescence microscopy, we have examined the local distribution of fluorescently labelled macromolecules released from an ethylene-vinyl acetate copolymer matrix into unstirred layers of phosphate-buffered water and mid-cycle human cervical mucus. Diffusion coefficients in the fluid were determined by observing the concentration profiles as a function of time. Diffusion coefficients determined for fluorescein, bovine serum albumin, and three classes of human immunoglobulins (IgG, slgA and IgM) in phosphate-buffered water were in good agreement with literature values. For fluorescein, albumin and IgG, diffusion in mucus was comparable with diffusion in water: the largest molecule tested was slowed by only a factor of 3.

Dynamic mechanical analysis of some randomly-oriented viscoelastic short-fiber composites

The mechanical properties of two series of composites consisting of tanned leather fibers in an ethylene-vinyl acetate copolymer matrix were studied by means of tensile and dynamic mechanical tests. The effect of fiber content on Young's modulus and the viscoelastic properties was studied by using five distinct fiber concentrations. Dynamic measurements were carried out at a frequency of 11 Hz and temperatures from - 70 to 80°C. The applicability of the Hashin correspondence principle was tested in order to provide a better understanding of the fiber content effect on the viscoelastic properties of these composites.

Controlled release of insulin from polymer matrices. In vitro kinetics.

A biocompatible system was developed that permits continuous release of biologically active insulin from small polymer matrices. Powdered insulin particles were incorporated into an ethylene-vinyl acetate copolymer matrix. The presence of particulate insulin resulted in a matrix composed of tortuous channels and constricted pores through which release occurred. When aqueous release media permeated the matrix, the insulin dissolved and diffused slowly through this tortuous network. The large concentration of insulin within the matrix provided the driving force for release. Release kinetics from these insulin polymer matrices were enhanced by increasing the insulin solubility, the insulin powder particle size, the loading of insulin within the matrix, and the porosity of the matrix. Appropriate geometric design of the polymer matrix resulted in near-constant insulin release rates.

Features of the fracture of ultrathin fibres in extrudates of polymer blends

Theoretical and experimental studies of features of the fracture of liquid jets in Newtonian and non-Newtonian systems described in literature have been generalized. Experimental data on the fracture of ultrathin polyoxymethylene fibres in extrudates of blends (polyoxymethylene-ethylene-vinyl acetate copolymer) have been analyzed. The length of the disturbance wave causing fracture proved to be greater for viscoelastic systems than for the Newtonian ones. Ultrathin polyoxymethylene fibres in the ethylene-vinyl acetate copolymer matrix show maximum instability at a viscosity ratio that is close to unity. Viscoelastic properties of the medium affect the stability of the jets more than those of the dispersed phase.

Magnetic modulation of release of macromolecules from polymers.

Sustained-release systems were made by incorporating bovine serum albumin and magnetic steel beads in an ethylene-vinyl acetate copolymer matrix. When exposed to aqueous medium, the polymer matrix released the albumin slowly and continuously. Application of an oscillating magnetic field increased the release rate by as much as 100%. Intervals of 6-hr periods of magnetic exposure and nonexposure were alternated over a 5-day period, resulting in corresponding increases and decreases in release and establishing a pattern of modulated sustained release.

Controlled release of prednisolone from ethylene-vinyl acetate copolymer matrix.

Ethylene-vinyl acetate (EVA) copolymer was evaluated as a carrier for controlled release of prednisolone. The vinyl acetate content of EVA copolymer varied from 8 to 33% w/w. Increase in vinyl acetate comonomer content of EVA copolymer matrix brought about an increase in the release rate. The release rate could be controlled by modifying the ethylene-vinyl acetate ratio in the polymer matrix. Fabrication parameters such as matrix coating and drug content also significantly affected the release kinetics. Matrices composed of EVA copolymer could be useful vehicles for the controlled release of the corticosteroid.

Effect of comonomer ratio on hydrocortisone diffusion from sustained-release composite capsules.

The daily in vitro release of hydrocortisone from composite polymer capsules is reported here for over 120 days. Increase in vinyl acetate comonomer content of the ethylene-vinyl acetate copolymer matrix brought about an increase in the diffusion rate. Variation in the initial drug content of the capsules from 40 mg to 20 mg affects the daily drug release less significantly than the variation in copolymer ratio. The correlation between vinyl acetate comonomer content and the percent crystallinity of the copolymer matrix is suggested as one of the possible major factors in controlling diffusion rate from this drug-polymer system. The diffusion constant (D) calculated was 0.212 X 10(10) cm2/sec when the copolymer carrier has 30% vinyl acetate content and 0.430 X 10(11) cm2/sec when the copolymer carrier has 20% vinyl acetate content for capsules with 20 mg initial drug content, and 0.118 X 10(-11) cm2/sec and 0.226 X 10(-11) cm2/sec, respectively, for capsules with 40 mg initial drug content.