Monolithic Matrices Research Articles

A Modular Platform for Cytocompatible Hydrogels with Tailored Mechanical Properties Based on Monolithic Matrices and Particulate Building Blocks.

We establish a versatile hydrogel platform based on modular building blocks that allows the design of hydrogels with tailored physical architecture and mechanical properties. We demonstrate its versatility by assembling (i) a fully monolithic gelatin methacryloyl (Gel-MA) hydrogel, (ii) a hybrid hydrogel composed of 1:1 Gel-MA and gelatin nanoparticles, and (iii) a fully particulate hydrogel based on methacryloyl-modified gelatin nanoparticles. The hydrogels were formulated to exhibit the same solid content and comparable storage modulus but different stiffness and viscoelastic stress relaxation. The incorporation of particles resulted in softer hydrogels with enhanced stress relaxation. Murine osteoblastic cells cultured in two-dimensional (2D) on hydrogels showed proliferation and metabolic activity comparable to established collagen hydrogels. Furthermore, the osteoblastic cells showed a trend of increased cell numbers, cell expansion, and more defined protrusions on stiffer hydrogels. Hence, modular assembly allows the design of hydrogels with tailored mechanical properties and the potential to alter cell behavior.

Development of an amorphous based sustained release system for apremilast a selective phosphodiesterase 4 (PDE4) inhibitor

Apremilast is a selective PDE4 inhibitor and has been approved for several inflammatory disorders. It is classified as a BCS-IV drug and has 7 polymorphic forms. In this research we report the development of an ASD based sustained-release (SR) drug delivery system. A simplified material sparing ASD formulation approach was employed to identify ideal carrier polymers for optimum drug loadings. HPMCAS-M at 20% and Copovidone at 40% drug loadings were selected as the lead formulations. A stable single-phase amorphous system of apremilast via spray drying was created and fully characterized by mDSC, XRPD, DMA, micro-dissolution, dissolution, and accelerated stability analysis. Micro-dissolution study of ASD confirmed attainment and maintenance of supersaturated state over 3 h. ASD showed 8-fold higher solubility relative to its crystalline counterpart. Novel monolithic and bilayer SR HPMC tablet matrices containing 30 mg or 60 mg of ASD system were manufactured. Tablets during dissolution exhibited gradual swelling, erosion, and disentanglement over 15–20-hours with over 90% drug released. The designed SR amorphous based matrix system showed ability to increase apremilast solubility, dissolution rate, and inhibit recrystallization or polymorphic interconversion by stabilizing its amorphous form. This new development may allow for once-daily drug administration and improve both bioavailability and patient compliance.

Thermogalvanic and Thermocapacitive Behavior of Superabsorbent Hydrogels for Combined Low-Temperature Thermal Energy Conversion and Harvesting

Around two-thirds of the energy generated by the society is lost as waste heat. Thermogalvanic cells can continuously convert thermal energy directly into electrical energy. Conversely, thermocapacitors can convert and store thermal energy as thermocapacitance. Here, we report two superabsorbent monolithic polymer hydrogel matrices designed through vessel-templated synthesis, which act as soft host materials for extremely high concentrations of redox-active ions, namely, [Fe(CN)6]3–/4– and Fe2+/3+. These highly charged superabsorbent hydrogels were found to improve both electrocatalysis and ohmic resistance of the hosted redox couples, preventing electrolyte leakage, and enable the ability to perform both thermogalvanic conversion and thermocapacitive storage. An unoptimized maximum thermogalvanic power density was observed at ca. 95 mW m–2 (ΔT of 20 K), on par with other reported gelled systems. An optimized thermocapacitance density of ca. 220 F cm–2 was achieved, which is 15-fold higher than the highest previously reported. These novel systems therefore present new possibilities in both the harvesting and storage of low-grade waste thermal energy.

Design and characterization of Kerberos: a 48-channel analog pulse processing and data acquisition platform

A multi-channel data processing and acquisition system based on an analog ASIC (SFERA) has been designed and realized. The platform, called Kerberos, is suitable for the readout of large arrays of Silicon Drift Detector (SDD) for X-ray, γ-ray and electron spectroscopy applications. Each one of its 48 inputs is equipped with a 9th order semi-Gaussian shaping amplifier with programmable peaking time (0.5, 1, 2, 3, 4 and 6 ). The pulse amplitudes are multiplexed into three 16-bit high linearity SAR ADCs and digitized into an Artix-7 FPGA module. Kerberos will be used for the characterization of monolithic SDD matrices for the TRISTAN project. Many different readout strategies can be selected on Kerberos Graphic User Interface: for TRISTAN it has been decided to use a full detector readout strategy, with maximum input throughput of about 166 kcount/s. This work presents a full characterization of this scalable platform and its use with several detectors types (SDD, micro-strips) in X-ray, gamma and beta spectroscopy.

The potential use of a gyroid structure to represent monolithic matrices for bioseparation purposes: Fluid dynamics and mass transfer analysis via CFD

This work describes the application of the gyroid model to represent a cryogel structure whose mass and momentum transport were investigated via Computational Fluid Dynamics (CFD) simulations. Initially, a gyroid was built using a computer platform and was morphologically characterized in terms of the tortuosity distribution, porosity and specific surface area. Hydrodynamic characteristics were then obtained, including permeability, pressure drop and Residence Time Distribution (RTD). Analyzing the velocity field, a heterogeneous flow was observed due to curve obstacles. This phenomenon was more noticeable at high flow rates due to lower contraction of the RTD curve which results in undesired conditions for the adsorption process. From a scaling analysis, mass transfer is governed by advection, adsorption and axial dispersion. Finally, there was a close agreement between the experimental and predicted breakthrough for different flow rates, indicating that the gyroid model was adequate to describe the flow, mass transfer and adsorption profile in the cryogel matrix. This is the first time that gyroid architecture is used to portray and simulate a bioseparation process in a cryogel chromatographic column.

Improvement of thermal conductivity of carbonaceous matrix in monolithic Al2O3–C refractory composite by surface-modified graphites

The thermal conductivity of the matrix part of alumina – carbon unshaped refractory has been estimated to accurately interpret its thermophysical and thermomechanical behavior. The properties of precalcined composite matrix containing either as-received or surface-modified graphite in equal quantity (20.0 wt%) have been investigated at three different temperatures (110,550,900 °C). The thermal compatibility or degradation of both kinds of carbonaceous matrices had been correlated with respective scanning electron microscope (SEM) and energy dispersive spectroscopy (EDS) analyses. The monolithic matrices were also subjected to X-ray diffraction (XRD) studies to distinguish between their phase evolution patterns. A synergestic study on an equivalent graphite-free formulation was also carried out. The thermal shock resistance profile of respective castables had been addressed to confirm the superiority of surface-treated graphites. Nanoengineering at graphite surface was conceived by Rietveld analysis of the (004) peak that substantiated the additional influence of calcium aluminate coating on selective clumping and partial exfoliation of graphite sheets.

Aerodynamics of Monolithic Matrices for Supporting Solid Reactant or Catalyst

Heterogeneous solid/fluid chemical reactions—as well as reactions dependent on solid catalysts—require spreading the active solid substance on the largest accessible area. The solution is a thin layer covering as much as possible convoluted surface of an inert support. This is nowadays the internal surface of narrow parallel passages. The supporting body is usually ceramic, its passages now mostly of square cross section. Reliable detailed knowledge of pressure drop across the set of passages has to be available, especially for flow control based on fluid property changes (e.g., with temperature or fluid composition). This paper presents results of laboratory measurements as well as numerical flowfield computations of the passage flows, with discovered universal law.

An insight into chiral monolithic stationary phases for enantioselective high-performance liquid chromatography applications.

In this review, three main classes of chiral monolithic stationary phases, namely silica-, organic polymer-, and hybrid-based monolithic stationary phases, are covered. Their preparations, applications, and advantages compared with the conventional-packed and open-tubular capillary columns are discussed. A detailed description of the different types and techniques used for the introduction of chiral selectors into the monolithic matrices such as immobilization, functionalization, coating, encapsulation, and bonding. Special emphasis is given to the recent developments of chiral selectors in HPLC monolithic stationary phases during the past 18 years.

Enhancements in sugar immobilization in polymeric macroporous matrices for affinity capture

ABSTRACTThe use of macroporous monolithic matrices in the purification of biocompounds is constantly growing and developing. In this work, the objective was to optimize the quantity of N‐acetyl‐D‐glucosamine (D‐GlcNAc) immobilized on the surface of macroporous polymeric cryogels for capture of lectins from less clarified solutions. Surface response methodology was applied and it was observed that the immobilization temperature of the glutaraldehyde (GLU) and the D‐GlcNAc concentration influenced the amount of sugar immobilized. The matrices produced with 1.1% of allyl glycidyl ether were functionalized by GLU. Optimal maximum condition was obtained with mean value of 160.39 ± 26.38 mg of D‐GlcNAc immobilized per gram of dry cryogel. Characterization analyses of the matrices showed that the activation process was effective, maintaining the macroporous structure and physical characteristics. The adsorbents produced were tested for capture of lectins from a crude protein solution of barley. At tested conditions, adsorbent capture around 11% of protein in solution but reduce the hemaglutinating capacity in 40%, demonstrating its selectivity. The cryogels functionalized with D‐GlcNAc present potential for use in capture compounds by affinity with carbohydrates, such as lectins. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019, 136, 47956.

Leachability and Microstructural Analysis of Clay and Lime Stabilized/Solidified Polluted Sediment – Long-Term Performance

The objective of this study is to enable a better understanding of the effectiveness of solidification/stabilization (S/S) technique in treating polluted sediment, and provide the much needed validation of the longevity of the technology. In this research kaolinite and montmorillonite, with a certain proportion of lime, were used for S/S treatment of sediment polluted with metals. Leachability of metals was examined using the toxicity characteristic leaching procedure (TCLP) and the German standard leaching test (DIN 3841-4 S4) prescribed in national legislative. Results indicated successful S/S treatment using both clays and lime, from the aspect of all leached metals even with pH variations over time and slight changes in structural integrity of specimens. X-ray diffraction (XRD), scanning electron microscope (SEM) analyses and porosity measurement were also performed on the prepared monolithic matrices. XRD qualitative and semi-quantitative analysis proved hydration and pozzolanic product formation with increase in their content and finer crystallites formation over time. SEM analysis confirmed the presence of morphologically dense and stable structures while pore size distribution indicated on mesoporous matrices with ongoing compaction over time. Generally, structural microanalysis indicated the formation of hardened matrices over time and hydration process has been fully completed and further carbonation took place. Unconfined compressive strength measurement gave the satisfying results and matured monolite with 30 % of montmorillonite and 10 % of lime can be considered potentially applicable as non-load-bearing material. In summary, all results indicated that this kind of S/S treatment can achieve satisfactory durability and represent reliable and economically feasible technique for long-term remediation of metal polluted sediment.

Characterisation of AMS H35 HV-CMOS monolithic active pixel sensor prototypes for HEP applications

Monolithic Active Pixel Sensors (MAPS) produced in High Voltage CMOS (HV-CMOS) technology are being considered for High Energy Physics applications due to the ease of production and the reduced costs. Such technology is especially appealing when large areas to be covered and material budget are concerned. This is the case of the outermost pixel layers of the future ATLAS tracking detector for the High Luminosity LHC. For experiments at hadron colliders, radiation hardness is a key requirement which is not fulfilled by standard CMOS sensor designs that collect charge by diffusion. This issue has been addressed by depleted active pixel sensors in which electronics are embedded into a large deep implantation ensuring uniform charge collection by drift. Very first small prototypes of hybrid depleted active pixel sensors have already shown a radiation hardness compatible with the ATLAS requirements. Nevertheless, to compete with the present hybrid solutions a further reduction in costs achievable by a fully monolithic design is desirable. The H35DEMO is a large electrode full reticle demonstrator chip produced in AMS 350 nm HV-CMOS technology by the collaboration of Karlsruher Institut für Technologie (KIT), Institut de F'isica d'Altes Energies (IFAE), University of Liverpool and University of Geneva. It includes two large monolithic pixel matrices which can be operated standalone. One of these two matrices was characterised at beam test before and after irradiation with protons and neutrons. Results demonstrated the feasibility of producing radiation hard large area fully monolithic pixel sensors in HV-CMOS technology. H35DEMO chips with a substrate resistivity of 200 Ωcm} irradiated with neutrons showed a radiation hardness up to a fluence of 1×1015 neq/cm2 with a hit efficiency of about 99% and a noise occupancy lower than 10-6 hits in a LHC bunch crossing of 25 ns at 150 V.

Evaluating the conventional mixing grades of demolished tiles aggregate concrete and mortar for sustainable use

Demolished marble and ceramic clay tiles waste management are one of the greatest concerns for sustainable development nowadays. The reason behind that chemical components of these two substances create a serious threat to the biodiversity. Consequently, this study aims to find the scope of applying marble and ceramic clay tiles wastes as green materials through immobilizing the potential contaminants in the structural bond of concrete and mortar. In favour of this, four widely used compositions such as 1:1:2 (OPC: FA: CA), 1:1.5:3, 1:2:4 and 1:3:6 for concrete specimens as well as 1:1 (OPC: FA), 1:1.5, 1:2 and 1:3 for mortar were selected as surrogate composition, where both wastes was substituted by 20% of the total volume of both natural aggregates. The study analyzed the relationship between the engineering characteristics of monolithic matrices and migration behavior of Ca2+ and Mg2+, which are abundantly available in the adopted demolished aggregates. The research revealed that releasing content of Ca2+ and Mg2+ from the representative samples increased with the increase of demolished aggregate content, void space and water absorption ratio, as well as with the reduction in compressive strength, density and coefficient of permeability. Furthermore, the combination 1:3:6 for concrete and 1:3 for mortar specimens showed that the total transport content of Ca2+ and Mg2+ exceeded the standard for disposal in the earth surface in static and hydraulic pressure leaching test and not safe for land disposal. The remaining employed mixtures of both cases exhibited the satisfactory level with non-pollutant in which entrapment of the measured ions ranged from 99.5% to 97.2%. Finally, the outcomes can be a potential option in producing eco-friendly construction materials by utilizing the concern wastes.

Controlled release of glibenclamide from monolithic silica subdermal implants produced by the sol-gel process and its use for hyperglycaemia treatment in a murine model

Glibenclamide is an anti-hyperglycaemic drug that is commonly used for the treatment of type 2 diabetes mellitus and has promising new medical indications. However, this drug is associated with high rates of serious hypoglycaemic episodes as a result of its pharmacological activity. Administering the drug through controlled release delivery systems could reduce the incidence of these episodes. In this study, glibenclamide silica monolithic xerogel implants for subdermal application (GMSIx) were developed using the sol-gel technique for matrix synthesis with TEOS with different drying conditions (environmental, 60, 90, and 120 °C, which were named as GMSIE, GMSI60, GMSI90, and GMSI120, respectively). The inclusion of the drug in monoliths was monitored by DSC, FTIR, and PXRD. The effect of drying conditions on the morphology, moisture content, hardness, dosage uniformity, surface characteristics, and drug release mechanism of glibenclamide from the matrices was systematically investigated. Oral Glucose Tolerance Tests were performed with mice to evaluate the efficacy of the GMSI in maintaining blood glucose levels. Glibenclamide was completely included in a non-crystalline solid form in the matrixes. The moisture content, hardness, dosage uniformity, and surface characteristics depend on the drying conditions. The monolithic matrices showed a mesoporous surface with high surface area, and a narrower pore size distribution occurred for GMSI60. GMSIE and GMSI60 showed non-Fickian anomalous Korsmeyer-Peppas glibenclamide release kinetics. GMSI90 and GMSI120 showed controlled release of the drug through dissolution. When GMSI60 was administered to mice, glucose blood levels were effectively maintained despite a high oral glucose load in the animals, showing a sustained effect of the drug released from this new sol-gel drug delivery system.

Self-stabilized chitosan and its complexes with carboxymethyl starch as excipients in drug delivery

This study focuses on the behavior of chitosan (CHI) and its polyelectrolyte complexes with carboxymethyl starch (CMS) used as monolithic matrices with acetaminophen as drug tracer. Two different chitosan grades were tested alone or associated in various ratios with CMS as excipients for tablets obtained by direct compression. The degree of deacetylation (DDA) of CHI, estimated from 1H NMR and FTIR data, was correlated with X-ray diffraction and scanning electron microscopy (SEM) to evaluate structural organization of the monolithic matrices. In vitro drug dissolution assays showed major differences in CHI kinetic profiles between tablets exposed to acidic medium for 2h (to mimick gastric passage) prior to dissolution in simulated intestinal fluid (SIF), and those administered directly to SIF. Prior exposure to acidic SGF conducted to longer dissolution profiles (release completed after 16 h) and preservation of tablet shape, whereas tablets directly incubated in SIF were rapidly disintegrated. The improved properties of chitosan matrices exposed to SGF may be related to an outer compact coating layer (visible in SEM). The effect of self-stabilization of chitosan in acidic medium was compared to that due to formation of polyelectrolyte complexes (PEC) in co-processed polymeric systems (CHI:CMS). The self-formed membrane following exposure to gastric acidity appears to help maintaining tablet integrity and allows higher drug loading, recommending CHI and its complexes with CMS as excipients for drug delivery.

Frontal dynamics of erythromycin sorption on monolithic molecularly imprinted polymer sorbents

The effect the flow rate of a mobile phase has on the frontal dynamics of antibiotic erythromycin sorption by monolithic molecularly imprinted polymeric sorbents based on 2-hydroxyethyl methacrylate and ethylene glycol dimethacrylate and their non-imprinted analog is studied. It is shown that erythromycin sorption proceeds in both the interglobular and intraglobular space of monolithic matrices, and the dynamic capacity of sorption can be regulated by changing the time of the experiment. The mobile phase flow rate at which the maximum specific bonding of the antibiotic by molecularly imprinted monolithic sorbents is observed is determined.

Discrete least-squares finite element methods

A finite element methodology for large classes of variational boundary value problems is defined which involves discretizing two linear operators: (1) the differential operator defining the spatial boundary value problem; and (2) a Riesz map on the test space. The resulting linear system is overdetermined. Two different approaches for solving the system are suggested (although others are discussed): (1) solving the associated normal equation with linear solvers for symmetric positive-definite systems (e.g. Cholesky factorization); and (2) solving the overdetermined system with orthogonalization algorithms (e.g. QR factorization). The finite element assembly algorithm for each of these approaches is described in detail. The normal equation approach is usually faster for direct solvers and requires less storage. The second approach reduces the condition number of the system by a power of two and is less sensitive to round-off error. The rectangular stiffness matrix of second approach is demonstrated to have condition number O(h−1) for a variety of formulations of Poisson’s equation. The stiffness matrix from the normal equation approach is demonstrated to be related to the monolithic stiffness matrices of least-squares finite element methods and it is proved that the two are identical in some cases. An example with Poisson’s equation indicates that the solutions of these two different linear systems can be nearly indistinguishable (if round-off error is not an issue) and rapidly converge to each other. The orthogonalization approach is suggested to be beneficial for problems which induce poorly conditioned linear systems. Experiments with Poisson’s equation in single-precision arithmetic as well as the linear acoustics problem near resonance in double-precision arithmetic verify this conclusion. The methodology described here is an outgrowth of the discontinuous Petrov–Galerkin (DPG) methodology of Demkowicz and Gopalakrishnan (2015). The strength of DPG is highlighted throughout, however, the majority of theory presented is more general. Extensions to constrained minimization principles are also considered throughout but are not analyzed in experiments.

Characterisation of novel prototypes of monolithic HV-CMOS pixel detectors for high energy physics experiments

An upgrade of the ATLAS experiment for the High Luminosity phase of LHC is planned for 2024 and foresees the replacement of the present Inner Detector (ID) with a new Inner Tracker (ITk) completely made of silicon devices. Depleted active pixel sensors built with the High Voltage CMOS (HV-CMOS) technology are investigated as an option to cover large areas in the outermost layers of the pixel detector and are especially interesting for the development of monolithic devices which will reduce the production costs and the material budget with respect to the present hybrid assemblies. For this purpose the H35DEMO, a large area HV-CMOS demonstrator chip, was designed by KIT, IFAE and University of Liverpool, and produced in AMS 350 nm CMOS technology. It consists of four pixel matrices and additional test structures. Two of the matrices include amplifiers and discriminator stages and are thus designed to be operated as monolithic detectors. In these devices the signal is mainly produced by charge drift in a small depleted volume obtained by applying a bias voltage of the order of 100V. Moreover, to enhance the radiation hardness of the chip, this technology allows to enclose the electronics in the same deep N-WELLs which are also used as collecting electrodes. In this contribution the characterisation of H35DEMO chips and results of the very first beam test measurements of the monolithic CMOS matrices with high energetic pions at CERN SPS will be presented.

Status of HVCMOS developments for ATLAS

This paper describes the status of the developments made by ATLAS HVCMOS and HVMAPS collaborations. We have proposed two HVCMOS sensor concepts for ATLAS pixels—the capacitive coupled pixel detector (CCPD) and the monolithic detector. The sensors have been implemented in three semiconductor processes AMS H18, AMS H35 and LFoundry LFA15. Efficiency of 99.7% after neutron irradiation to 1015 neq/cm2W has been measured with the small area CCPD prototype in AMS H18 technology. About 84% of the particles are detected with a time resolution better than 25 ns. The sensor was implemented on a low resistivity substrate. The large area demonstrator sensor in AMS H35 process has been designed, produced and successfully tested. The sensor has been produced on different high resistivity substrates ranging from 80 Ωcm to more than 1 kΩ. Monolithic- and hybrid readout are both possible. In August 2016, six different monolithic pixel matrices for ATLAS with a total area of 1 cm2 have been submitted in LFoundry LFA15 process. The matrices implement column drain and triggered readout as well as waveform sampling capability on pixel level. Design details will be presented.

Effects of specimen size and mix ratio on the nickel migration behavior of landfill waste mixed mortar

Landfill solid waste management system poses the potential source of silent wide-spread heavy metals like nickel poisoning in the entire ecosystem of nearby environment. Nickel containing demolish solid wastes are disposed at landfill zones to a great extent from where nickel migrate into the food chain through the surface water body as well as groundwater. Consequently, nickel exposure may cause different environmental problems. From this sense, it may be an attractive proposal to recycle the waste as a sustainable product. Herein is presented a long-term feasibility study on potential leaching behavioral pattern of nickel from different sizes and mixes based solidified landfill waste mixed mortar block. The calculated results revealed the larger sizes block entrapped more nickel content than the smaller in relation to the available for leaching. Moreover, the specimen bearing the higher amount of waste resulted the significant nickel immobilization within the crystalline structure. The study observed the fixation results 97.72%–99.35%, 97.08%–99.11%, 96.19%–98.58% and 95.86%–91.6% under the stabilizing agent to fine aggregate mixing combination 1:1, 1:1.5, 1:2 and 1:2.5 respectively where 30% of the total volume of fine aggregate was replaced by landfill waste. Although, mechanical strength test of all surrogate waste forms was also conducted that showed acceptable performance for land disposal, the current research pointing out that constructed green products were non-hazardous except the specimens having mixture ratio 1:2.5 because nickel ion release mechanism was observed under this ratio by surface decay or physical erosion of the monolithic matrices. Furthermore, semi-empirical based dominant leaching mechanism models were justified against the goodness of fit statistical parameters for interpreting the experimental observations of nickel transport profile where the adopted models possessed strong potential for predicting Ni content with high accuracy.

Carboxymethyl Starch Excipients for Drug Chronodelivery.

Carboxymethyl starch (CMS) is a pH-responsive excipient exhibiting also interesting properties for applications in delayed drug delivery systems. This work was aimed to investigate the release properties of monolithic and dry-coated tablets based on ionic sodium CMS and on protonated CMS, formulated with three model tracers: acetaminophen, acetylsalicylic acid (ASA), and sodium diclofenac. The sodium or protonated CMS were obtained from the same CMS synthesis by controlling the final pH of reaction media. The two forms of CMS were confirmed by the Fourier transform infrared spectroscopy. The in vitro dissolution profiles for monolithic and double core tablets were different and allowed a better understanding of characteristics of the two excipient forms. It was found that the protonated CMS exhibited a better stability in simulated gastric fluid in comparison to its sodium salt in monolithic dosage forms, whereas both excipients afforded a complete gastric protection of drugs when formulated as dry-coated dosages. Determination of water uptake and erosion rate of monolithic matrices based on the two CMS forms showed different mechanisms involved in the delivery of the three model active molecules in simulated intestinal media. When pancreatic enzymes were added in dissolution media, the drug release was accelerated showing that CMS is still a substrate for alpha-amylase. Both sodium and protonated starch excipients, formulated as dry-coated dosages, afforded a good gastro-protection and allowed a drug chronodelivery at various intervals up to 4-5h. They could be considered as an alternative for delayed delivery and a solvent-free coating procedure.