Viscoelasticity of a carbon nanotube-laden air-water interface.

The viscoelasticity of a carbon nanotube (CNT)-laden air-water interface was characterized using two different experimental methods. The first experimental method used a Langmuir-Pockels (LP) trough coupled with a pair of oscillating barriers. The second method is termed the Bicone-Trough (BT) method, where a LP trough was custom-built and fit onto a rheometer equipped with a bicone fixture to standardize the preparation and conditioning of a particle-laden interface especially at high particle coverages. The performance of both methods was evaluated by performing Fast Fourier Transform (FFT) analysis to calculate the signal-to-noise ratios (SNR). Overall, the rheometer-based BT method offered better strain control and considerably higher SNRs compared to the Oscillatory Barriers (OB) method that oscillated barriers with relatively limited positional and speed control. For a CNT surface coverage of 165 mg/m2 and a frequency of 100 mHz, the interfacial shear modulus obtained from the OB method increased from 39 to 57 mN/m as the normal strain amplitude increased from 1 to 3%. No linear viscoelastic regime was experimentally observed for a normal strain as small as 0.5%. In the BT method, a linear regime was observed below a shear strain of 0.1%. The interfacial shear modulus decreased significantly from 96 to 2 mN/m as the shear strain amplitude increased from 0.025 to 10%.

Numerical study of drop dynamics for inkjet based 3D printing of pharmaceutical tablets.

Interest in 3D printing has been growing rapidly especially in pharmaceutical industry due to its multiple advantages such as manufacturing versatility, personalization of medicine, scalability, and cost effectiveness. Inkjet based 3D printing gained special attention after FDA's approval of Spritam® manufactured by Aprecia pharmaceuticals in 2015. The precision and printing efficiency of 3D printing is strongly influenced by the dynamics of ink/binder jetting, which further depends on the ink's fluid properties. In this study, Computational Fluid Dynamics (CFD) has been utilized to study the drop formation process during inkjet-based 3D printing for piezoelectric and thermal printhead geometries using Volume of Fluid (VOF) method. To develop the CFD model commercial software ANSYS-Fluent was used. The developed CFD model was experimentally validated using drop watcher setup to record drop progression and drop velocity. During the study, water, Fujifilm model fluid, and Amitriptyline drug solutions were evaluated as the ink solutions. The drop properties such as drop volume, drop diameter, and drop velocity were examined in detail in response to change ink solution properties such as surface tension, viscosity, and density. A good agreement was observed between the experimental and simulation data for drop properties such as drop volume and drop velocity.

Pilot-scale binder jet 3D printing of sustained release solid dosage forms.

The additive nature and versatility of 3D printing show great promise in the rapid prototyping of solid dosage forms for clinical trials and mass customization for personalized medicine applications. This paper reports the formulation and process development of sustained release solid dosage forms, termed "printlets", using a pilot-scale binder jetting (BJT) 3D printer and acetaminophen (APAP) as the model drug. With the inclusion of hydroxypropyl methylcellulose (HPMC) as a release retardant polymer in the print powder, the drug release time of APAP increased considerably from minutes to hours. However, given the swelling propensity of HPMC, a thicker layer of powder must be laid down during printing to avoid any shape distortion of the printlets. For a fixed print volume, the level of binder saturation (i.e., ratio between the liquid binder and powder in the as-printed sample) is inversely proportional to the thickness of the spread powder layer. An increase in the spread powder layer inadvertently resulted in a lower level of binder saturation and consequently weaker printlets. By increasing the level of binder saturation with jetting from more print heads, the mechanical strength of printlets containing 18% HPMC was successfully restored. The resultant printlets have a drug release time of 3.5 h and a breaking force of 12.5 kgf that is comparable to the fast-disintegrating printlets containing no HPMC and surpasses manually pressed tablets with the same HPMC content.

Pharmaceutical applications of powder-based binder jet 3D printing process - A review.

Pharmaceutical applications of the 3D printing process have recently matured, followed by the FDA approval of Spritam, the first commercial 3D printed dosage form. Due to being a new technology in the conventional dosage formulation field, there is still a dearth of understanding in the 3D printing process regarding the effect of the raw materials on the printed dosage forms and the plausibility of using this technology in dosage development beyond the conventional ways. In this review, the powder-based binder jet 3D printing (BJ3DP) process and its pharmaceutical applications have been discussed, along with a perspective of the formulation development step. The recent applications of BJ3DP in pharmaceutical dosage development, the advantages, and limitations have further been discussed here. A discussion of the critical formulation parameters that need to be explored for the preformulation study of the solid oral dosage development using the BJ3DP process is also presented.

Development of a pilot-scale HuskyJet binder jet 3D printer for additive manufacturing of pharmaceutical tablets.

This paper reports a custom-built binder jet 3D printer for pilot-scale manufacturing of pharmaceutical tablets. The printer is equipped with high-throughput piezoelectric inkjet print heads and allows direct control of several key process parameters, including the build layer thickness, amount of jetted liquid binder, and powder spreading rate. The effects of these parameters on the properties of the as-printed tablets were studied using a powder mixture of lactose monohydrate and Kollidon® VA64 (KL) and an aqueous binder containing 5% of KL. The appropriate processing windows for two different powder spreading rates were identified, and the final properties of the printed samples were explained using a dimensionless "degree of overlap" parameter which is defined as the ratio between the penetrating depth of the binder into the powder and the build layer thickness. Lastly, 10% of indomethacin was added to the powder feedstock as a model drug. Drug-loaded tablets were produced at a rate of 32 tablets/min, having an average breaking force of 9.4 kgf, a friability of 2.5%, and an average disintegration time of 8 s. These properties are comparable to commercially available tablets and represent one of the best values reported in the literature of 3D printed tablets thus far.

Impact of powder-binder interactions on 3D printability of pharmaceutical tablets using drop test methodology.

In this study, a pre-screening test has been developed for the binder-jet 3D printing process (BJ3DP) which has been validated using statistical analysis. The pre-screening test or drop test has been adapted from the wet granulation field and modified later on to be used for tablet manufacturing in BJ3DP. Initially, a total of eight powders and ten water-based binder solutions have been introduced in the preliminary test to understand the powder-binder interactions. Afterward, based on the preliminary test results, three blends were developed which had undergone the same drop test. All these powder and binder combinations were then used for 3D printing. The key parameters such as mechanical strength and shape factors of the drop test agglomerates and 3D printed tablets were then compared using multiple linear regressions. Few dimensionless parameters were introduced in this study such as binding capacity and binding index to capture the printability properties of the powders used in this study. Significant relations (p<0.05) were found between the drop test and the BJ3DP process. Application of drop test was carried out to establish a prescreening test, ii) to develop new blend formulations as well as iii) to develop a fundamental understanding of powder-binder interaction during BJ3DP process.

Toward Long-Term Accurate and Continuous Monitoring of Nitrate in Wastewater Using Poly(tetrafluoroethylene) (PTFE)-Solid-State Ion-Selective Electrodes (S-ISEs).

Long-term accurate and continuous monitoring of nitrate (NO3-) concentration in wastewater and groundwater is critical for determining treatment efficiency and tracking contaminant transport. Current nitrate monitoring technologies, including colorimetric, chromatographic, biometric, and electrochemical sensors, are not feasible for continuous monitoring. This study addressed this challenge by modifying NO3- solid-state ion-selective electrodes (S-ISEs) with poly(tetrafluoroethylene) (PTFE, (C2F4)n). The PTFE-loaded S-ISE membrane polymer matrix reduces water layer formation between the membrane and electrode/solid contact, while paradoxically, the even more hydrophobic PTFE-loaded S-ISE membrane prevents bacterial attachment despite the opposite approach of hydrophilic modifications in other antifouling sensor designs. Specifically, an optimal ratio of 5% PTFE in the S-ISE polymer matrix was determined by a series of characterization tests in real wastewater. Five percent of PTFE alleviated biofouling to the sensor surface by enhancing the negative charge (-4.5 to -45.8 mV) and lowering surface roughness (Ra: 0.56 ± 0.02 nm). It simultaneously mitigated water layer formation between the membrane and electrode by increasing hydrophobicity (contact angle: 104°) and membrane adhesion and thus minimized the reading (mV) drift in the baseline sensitivity ("data drifting"). Long-term accuracy and durability of 5% PTFE-loaded NO3- S-ISEs were well demonstrated in real wastewater over 20 days, an improvement over commercial sensor longevity.

Silk fibroin reactive inks for 3D printing crypt-like structures.

A reactive silk fibroin ink formulation designed for extrusion three-dimensional (3D) printing of protein-based hydrogels at room temperature is reported. This work is motivated by the need to produce protein hydrogels that can be printed into complex shapes with long-term stability using extrusion 3D printing at ambient temperature without the need for the addition of nanocomposites, synthetic polymers, or sacrifical templates. Silk fibroin from the Bombyx mori silkworm was purified and synthesized into reactive inks by enzyme-catalyzed dityrosine bond formation. Rheological and printing studies showed that tailoring the peroxide concentration in the reactive ink enables the silk to be extruded as a filament and printed into hydrogel constructs, supporting successive printed layers without flow of the construct or loss of desired geometry. To enable success of longer-term in vitro studies, 3D printed silk hydrogels were found to display excellent shape retention over time, as evidenced by no change in construct dimensions or topography when maintained for nine weeks in culture medium. Caco-2 (an intestinal epithelial cell line) attachment, proliferation, and tight junction formation on the printed constructs was not found to be affected by the geometry of the constructs tested. Intestinal myofibroblasts encapsulated within reactive silk inks were found to survive shearing during printing and proliferate within the hydrogel constructs. The work here thus provides a suitable route for extrusion 3D printing of protein hydrogel constructs that maintain their shape during printing and culture, and is expected to enable longer-term cellular studies of hydrogel constructs that require complex geometries and/or varying spatial distributions of cells on demand via digital printing.

Binder-Jet 3D Printing of Indomethacin-laden Pharmaceutical Dosage Forms.

Emerging 3D printing technologies offer an exciting opportunity to create customized 3D objects additively from a digital design file. 3D printing may be further leveraged for personalized medicine, clinical trial, and controlled release applications. A wide variety of 3D printing methods exists, and many studies focus on extrusion-based 3D printing techniques that closely resemble hot melt extrusion. In this paper, we explore different pharmaceutical-grade feedstock materials for creating tablet-like dosage forms using a binder jet 3D printing method. In this method, pharmaceutical-grade powders are repeatedly spread onto a build plate, followed by inkjet printing a liquid binder to selectively bind the powders in a predetermined pattern. The physical properties of the pharmaceutical-grade powders and binders have been characterized and a molding method has been developed to select appropriate powder and binder materials for subsequent printing experiments. There was a correlation between the breaking forces of the molded and printed samples, but no clear correlation was observed for disintegration time, which was primarily controlled by the higher porosity of the printed samples. The breaking force and disintegration properties of as-printed and post-processed samples containing indomethacin as an active pharmaceutical ingredient have been measured and compared with relevant literature data.

Formulation design for inkjet-based 3D printed tablets.

The drug loading efficiency was evaluated using a binder-jet 3D printing process by incorporating an active pharmaceutical ingredient (API) in ink, and quantifying the printability property of ink solutions. A dimensionless parameter Ohnesorge was calculated to understand the printability property of the ink solutions. A pre-formulation study was also carried out for the raw materials and printed tablets using thermal analysis and compendial tests. The compendial characterization of the printed tablets was evaluated with respect to weight variation, hardness, disintegration, and size; Amitriptyline Hydrochloride was considered as the model API in this study. Four concentrations of the API ink solutions (5, 10, 20, 40 mg/mL) were used to print four printed tablet batches using the same tablet design file. The excipient mixture used in the study was kept the same and consists of Lactose monohydrate, Polyvinyl pyrrolidone K30, and Di-Calcium phosphate Anhydrate. The minimum drug loading achieved was 30 µg with a minimal variation (RSD) of <0.26%. The distribution of the API on the tablet surface and throughout the printed tablets were observed using SEM-EDS. In contrast, the micro-CT images of the printed tablets indicated the porous surface structure of the tablets. The immediate release properties of the printed tablets were determined using a dissolution study in a modified USP apparatus II.

Influence of Manufacturing Process Variables on the Properties of Ophthalmic Ointments of Tobramycin.

PURPOSE: The main purpose of this study was to evaluate qualitative (Q1) and quantitative (Q2) equivalent oleaginous ophthalmic ointments of tobramycin (TOB) with different physicochemical properties and identify critical process/quality attributes using various in vitro methods of characterization. METHODS: Various sources of petrolatum and TOB, and two mixing methods were employed to generate Q1/Q2 equivalent ointments. Characterization studies included content uniformity, microscopy, modulated temperature differential scanning calorimetry (MTDSC), gas chromatography-mass spectrometry (GC/MS), thermogravimetric analysis (TGA) and rheology. RESULTS: The particle size distribution of TOB influenced the content uniformity of ointments. Differences in the MTDSC endothermic and exothermic peaks of TOB suggested the presence of different polymorphic forms. GC/MS revealed variations in the composition and distribution of linear and branched hydrocarbons of petrolatums. Differences were also observed in the TGA derivative weight loss peaks demonstrating differences in the composition of petrolatum that may be the source of the observed variations in the rheological parameters of the ointments. CONCLUSIONS: Source and composition of the petrolatum played a more critical role in determining the rheological properties compared to the method of preparation. Results demonstrated the impact of the source of TOB, excipients and manufacturing processes on the quality attributes of TOB ophthalmic ointments.

The Margination of Particles in Areas of Constricted Blood Flow.

Stroke is a leading cause of death globally and is caused by stenoses, abnormal narrowings of blood vessels. Recently, there has been an increased interest in shear-activated particle clusters for the treatment of stenosis, but there is a lack of literature investigating the impact of different stenosis geometries on particle margination. Margination refers to the movement of particles toward the blood vessel wall and is desirable for drug delivery. The current study investigated ten different geometries and their effects on margination. Microfluidic devices with a constricted area were fabricated to mimic a stenosed blood vessel with different extent of occlusion, constricted length, and eccentricity (gradualness of the constriction and expansion). Spherical fluorescent particles with a diameter of 2.11 µm were suspended in blood and tracked as they moved into, through, and out of the constricted area. A margination parameter, M, was used to quantify margination based on the particle distribution after velocity normalization. Experimental results suggested that a constriction leads to an enhanced margination, whereas an expansion is responsible for a decrease in margination. Further, margination was found to increase with increasing percent occlusion and constriction length, likely a result of higher shear rate and longer residence time, respectively. Margination decreases as the stenosis geometry becomes more gradual (eccentricity increases) with the exception of a sudden constriction/expansion geometry. The findings demonstrate the importance of geometric effects on margination and call for detailed numerical modeling and geometric characterization of the stenosed areas to fully understand the underlying physics.

Dissolution and Characterization of Boron Nitride Nanotubes in Superacid.

Boron nitride nanotubes (BNNTs) are of interest for their unique combination of high tensile strength, high electrical resistivity, high neutron cross section, and low reactivity. The fastest route to employing these properties in composites and macroscopic articles is through solution processing. However, dispersing BNNTs without functionalization or use of a surfactant is challenging. We show here by cryogenic transmission electron microscopy that BNNTs spontaneously dissolve in chlorosulfonic acid as disentangled individual molecules. Electron energy loss spectroscopy of BNNTs dried from the solution confirms preservation of the sp2 hybridization for boron and nitrogen, eliminating the possibility of BNNT functionalization or damage. The length and diameter of the BNNTs was statistically calculated to be ∼4.5 µm and ∼4 nm, respectively. Interestingly, bent or otherwise damaged BNNTs are filled by chlorosulfonic acid. Additionally, nanometer-sized synthesis byproducts, including boron nitride clusters, isolated single and multilayer hexagonal boron nitride, and boron particles, were identified. Dissolution in superacid provides a route for solution processing BNNTs without altering their chemical structure.

Direct Tracking of Particles and Quantification of Margination in Blood Flow.

Margination refers to the migration of particles toward blood vessel walls during blood flow. Understanding the mechanisms that lead to margination will aid in tailoring the attributes of drug-carrying particles for effective drug delivery. Most previous studies evaluated the margination propensity of these particles via an adhesion mechanism, i.e., by measuring the number of particles that adhered to the channel wall. Although particle adhesion and margination are related, adhesion also depends on other factors. In this study, we quantified the margination propensity of particles of varying diameters (0.53, 0.84, and 2.11 µm) and apparent wall shear rates (30, 61, and 121 s-1) by directly tracking fluorescent particles flowing through a microfluidic channel. The margination parameter, M, is defined as the total number of particles found within the cell-free layers normalized by the total number of particles that passed through the channel. In this study, an M-value of 0.2 indicated no margination, which was observed for all particle sizes in water. In the case of blood, larger particles were found to have higher M-values and thus marginated more effectively than smaller particles. The corresponding M-values at the device outlet were 0.203, 0.223, and 0.285 for 0.53-, 0.84-, and 2.11-µm particles, respectively. At the inlet, the M-values for all particle sizes in blood were <0.2, suggesting that non-fully-developed flow and constriction may lead to demargination. For particle velocities transverse to the flow direction (vy), all particle sizes showed a larger standard deviation of vy as well as a higher effective diffusivity when the particles were suspended in blood relative to water. These higher values are attributed to collisions between the blood cells and particles, further supporting recent simulation results. In terms of flow rates, for a given particle size, the higher the flow rate, the higher the M-value.

Controlling system components with a sound card: A versatile inkjet fluid testing platform.

In this paper, we demonstrate how to use a personal computer sound card to develop an experimental platform for evaluating the jettability and jetting behavior of inkjet fluids. The test fluid is driven out of a nozzle acoustically using a loudspeaker, forming a jet. The subsequent jet breakup process is then captured using a stroboscopic light source and a camera. Instead of using a delay generator as in previous work, the current setup uses a computer sound card and audio amplifier to (i) generate actuation waveforms of arbitrary shapes and (ii) synchronize the jet actuation and imaging with a time precision close to 5 µs. To correct for any signal distortions caused by the built-in high pass filters of the sound card and amplifier, a numerical filter is created and applied before sending the desired signal to the sound card. Such correction method does not require physically modifying the hardware of the sound card or amplifier and is applicable to different waveforms and filters provided that the transfer function is correctly identified. The platform has been tested using 20% (v/v) glycerol in water as a model fluid. Combining this platform with digital image analysis further enables a quantitative assessment of parameters such as the volumes and positions of the jet and drop that are important for quality control and development of new ink formulations.

Surface pressure and microstructure of carbon nanotubes at an air-water interface.

This article reports the surface pressure and microstructure of two different types of carbon nanotubes (CNTs) at an air-water interface; namely, as-produced CNTs (nf-CNTs) and CNTs functionalized with carboxyl groups (f-CNTs). Both types of CNTs formed 3D aggregates upon compression using a Langmuir-Pockels trough. However, f-CNTs showed a lower degree of aggregation compared with that of nf-CNTs. This is attributed to the deprotonation of the carboxyl groups within the water subphase, leading to additional electrostatic repulsion between f-CNTs. For the same initial amount of CNTs spread onto the interface, the actual coverage of f-CNTs was higher than that of nf-CNTs at a given trough area. At high compression, f-CNTs formed aligned CNT domains at the interface. These 2D domains resembled 3D liquid-crystalline structures formed by excluded volume interactions. The denser packing and orientational ordering of f-CNTs also contributed to a compressional modulus higher than that of nf-CNTs, as calculated from the surface pressure isotherms. A Volmer equation of state was applied to model the measured surface pressure containing both thermodynamic and mechanical contributions. The Volmer model, however, did not consider the loss of CNTs from the interface due to 3D aggregation and consequently overestimated the surface pressure at high compression. The actual coverage of CNT during compression was back calculated from the model and was in agreement with the value obtained independently from optical micrographs. The findings of this work may have a broader impact on understanding the assembly and collective behavior of rod-like particles with a high aspect ratio at an air-water interface.

Facile synthesis of Co3O4@CNT with high catalytic activity for CO oxidation under moisture-rich conditions.

The catalytic oxidation reaction of CO has recently attracted much attention because of its potential applications in the treatment of air pollutants. The development of inexpensive transition metal oxide catalysts that exhibit high catalytic activities for CO oxidation is in high demand. However, these metal oxide catalysts are susceptible to moisture, as they can be quickly deactivated in the presence of trace amounts of moisture. This article reports a facile synthesis of highly active Co3O4@CNT catalysts for CO oxidation under moisture-rich conditions. Our synthetic routes are based on the in situ growth of ultrafine Co3O4 nanoparticles (NPs) (∼2.5 nm) on pristine multiwalled CNTs in the presence of polymer surfactant. Using a 1% CO and 2% O2 balanced in N2 (normal) feed gas (3-10 ppm moisture), a 100% CO conversion with Co3O4@CNT catalysts was achieved at various temperatures ranging from 25 to 200 °C at a low O2 concentration. The modulation of surface hydrophobicity of CNT substrates, other than direct surface modification on the Co3O4 catalytic centers, is an efficient method to enhance the moisture resistance of metal oxide catalysts for CO oxidation. After introducing fluorinated alkyl chains on CNT surfaces, the superhydrophobic Co3O4@CNT exhibited outstanding activity and durability at 150 °C in the presence of moisture-saturated feed gas. These materials may ultimately present new opportunities to improve the moisture resistance of metal oxide catalysts for CO oxidation.

Particle margination and its implications on intravenous anticancer drug delivery.

"Margination" refers to the movement of particles in flow toward the walls of a channel. The term was first coined in physiology for describing the behavior of white blood cells (WBCs) and platelets in blood flow. The margination of particles is desirable for anticancer drug delivery because it results in the close proximity of drug-carrying particles to the endothelium, where they can easily diffuse into cancerous tumors through the leaky vasculature. Understanding the fundamentals of margination may further lead to the rational design of particles and allow for more specific delivery of anticancer drugs into tumors, thereby increasing patient comfort during cancer treatment. This paper reviews existing theoretical and experimental studies that focus on understanding margination. Margination is a complex phenomenon that depends on the interplay between inertial, hydrodynamic, electrostatic, lift, van der Waals, and Brownian forces. Parameters that have been explored thus far include the particle size, shape, density, stiffness, shear rate, and the concentration and aggregation state of red blood cells (RBCs). Many studies suggested that there exists an optimal particle size for margination to occur, and that nonspherical particles tend to marginate better than spherical particles. There are, however, conflicting views on the effects of particle density, stiffness, shear rate, and RBCs. The limitations of using the adhesion of particles to the channel walls in order to quantify margination propensity are explained, and some outstanding questions for future research are highlighted.

Strong, light, multifunctional fibers of carbon nanotubes with ultrahigh conductivity.

Broader applications of carbon nanotubes to real-world problems have largely gone unfulfilled because of difficult material synthesis and laborious processing. We report high-performance multifunctional carbon nanotube (CNT) fibers that combine the specific strength, stiffness, and thermal conductivity of carbon fibers with the specific electrical conductivity of metals. These fibers consist of bulk-grown CNTs and are produced by high-throughput wet spinning, the same process used to produce high-performance industrial fibers. These scalable CNT fibers are positioned for high-value applications, such as aerospace electronics and field emission, and can evolve into engineered materials with broad long-term impact, from consumer electronics to long-range power transmission.

High-performance carbon nanotube transparent conductive films by scalable dip coating.

Transparent conductive carbon nanotube (CNT) films were fabricated by dip-coating solutions of pristine CNTs dissolved in chlorosulfonic acid (CSA) and then removing the CSA. The film performance and morphology (including alignment) were controlled by the CNT length, solution concentration, coating speed, and level of doping. Using long CNTs (∼10 µm), uniform films were produced with excellent optoelectrical performance (∼100 Ω/sq sheet resistance at ∼90% transmittance in the visible), in the range of applied interest for touch screens and flexible electronics. This technique has potential for commercialization because it preserves the length and quality of the CNTs (leading to enhanced film performance) and operates at high CNT concentration and coating speed without using surfactants (decreasing production costs).