Personalisation of warfarin therapy using thermal ink-jet printing

Three-dimensional (3D) bioprinting techniques, developed over the past two decades, have the potential to fabricate living, patient-specific tissues and organs for use in regenerative medicine (Kesti et al. 2016). Inkjet-based bioprinting is one of the oldest yet promising technologies, which combines the solid freeform fabrication process and precise cell placement in 2D and 3D. Typically, inkjet printing takes digital data of an image or character from a computer and reproduces it on to a material or substrate using ink drops in a noncontact mode (Mohebi and Evans 2002). In addition to its wide application in automation office tool, it has also been widely used in microengineering for printing electronic materials (Sirringhaus et al. 2000). Inkjet printer deposits controlled volume of ink in a layer-by-layer fashion to predefined locations on successive layers to form a 3D construct (Xu et al. 2008). Drop-on-demand (DOD) printers, a commonly used inkjet printers, are used for biological and nonbiological applications. The idea of printing of biological substances was introduced by Klebe after using HP thermal DOD inkjet printer to deposit collagen and fibronectin in 1988 (Klebe 1988). Later, Thomas Boland customized the thermal inkjet printer for printing living cells in a viable state (Wilson and Boland 2003). After this, scientists have made great progress in patterning molecules such as DNA, depositing proteins (Eric et al. 2009, Ilkhanizadeh et al. 2007, Miller et al. 2006), and printing tissues and organs by inkjet printing (Okamoto et al. 2000). The current focus of inkjet bioprinting is fabrication of 3D structures with clinically significant heights to extend its effectiveness in the direction of clinical applications. In this chapter, we discuss about the principle of inkjet bioprinting technology, types of inkjet printers in use, materials used for printing, and the critical parameters involved in this technique. Then, challenges associated with techniques and the future perspectives are also discussed.

To deliver maximum amount of paroxetine in shortest duration of time, the orodispersible films (ODF) were formulated and tested for their suitability as a carrier system. ODF were prepared by using hydroxypropyl methylcellulose and polyvinyl alcohol and different superdisintegrants at a specific proportion. The newly developed ODF were subjected to characterization for folding endurance, weight variations, thickness, disintegration time, drug release pattern and drug content. The surface morphology of orodispersible film was examined by means of scanning electron microscope. Moreover physical compatibility between the drug and excipients was guaranteed in the orodispersible film by Fourier transform infrared spectroscopy. It was found that all films prepared were transparent, smooth and elegant in appearance. ODF showed good folding endurance, uniform thickness, weight and drug content. The surface pH of all orodispersible film was found to be neutral and they disintegrate within few seconds. FTIR spectroscopy supported compatible among all excipients and they can be used together in formulation. It was concluded that stable paroxetine orodispersible films can be made by solvent casting technique with ultrafast dissolution rate.

In recent years, solid dosage forms have gained interest in pediatric therapy because they can provide valuable benefits in terms of dose accuracy and stability. Particularly for orodispersible films (ODFs), the literature evidences increased acceptability and dose flexibility. Among the various available technologies for obtaining ODFs, such as solvent casting, hot-melt extrusion, and ink printing technologies, the solvent-free preparation methods exhibit significant advantages. This study investigated Vacuum Compression Molding (VCM) as a solvent-free manufacturing method for the preparation of flexible-dose pediatric orodispersible films. The experimental approach focused on selecting the appropriate plasticizer and ratios of the active pharmaceutical ingredient, diclofenac sodium, followed by the study of their impacts on the mechanical properties, disintegration time, and drug release profile of the ODFs. Additional investigations were performed to obtain insights regarding the solid-state properties. The ODFs obtained by VCM displayed adequate quality in terms of their critical characteristics. Therefore, this proof-of-concept study shows how VCM could be utilized as a standalone method for the production of small-scale ODFs, enabling the customization of doses to meet the individual needs of pediatric patients.

In recent years, ink jet has emerged as one of the mainstream printing technologies. Since its market inception in 1985, Hewlett-Packard's thermal ink jet technology (TIJ) has evolved progressively from a 12 nozzle 96 dpi print head to a 300 nozzle 600 dpi print head. TIJ has made rapid progress enabling it to print text output on plain paper that challenges laser printers, and realistic photographic images that rival silver halide, at a low consumer price. Thermal ink jet technology continues to enjoy a greater unit market share than any other digital printing technology and all other ink jet technologies combined. The driving forces for the advancement of TIJ have been better, faster, and cheaper printers for consumers. These goals involve key attributes such as ink performance (gamut, sharpness, fastness), minimum deliverable colorant (drop volume), rate of colorant delivery (firing frequency, nozzle integration, firing chamber volume), and print engine cost per unit throughput. In this paper, key technology challenges for TIJ will be outlined. New materials and new processes that are required for the advancement of thermal ink jet printing are discussed. Recently, competing ink jet methods have (re-)emerged, notably piezoelectric ink jet. References will be made to piezoelectric ink jet when appropriate.© (1998) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

The advantages of digital printing are emerging into commercial printing. Deinking of inkjet prints is important because they will become a sizable portion of the waste stream. Thermal inkjet ink dispersions are water-based and under certain chemical environments can remain suspended in the process water during flotation, potentially causing discoloration in a closed-loop water system during deinking [1]. Newsprint has not been a major inkjet printing category for digital commercial inkjet prints but the recycling industry has expressed concern about the deinkability of this combination. Also, while newsprint is rarely used in the office, the advent of the commercial inkjet web press will see increasing interest in the recyclability of inkjet on newsprint media, since it provides the option for deployment of newsprint media for short-life (non-archival) printing. When inkjet inks are printed on newsprint, made from wood-containing pulp with lignin, which is then included in the papermaking furnish, the problem of process water darkening can be exacerbated under some chemical conditions. Ideally, the individual sub-micron pigments and molecular dyes in inkjet ink dispersions should be collected to form larger particles of the appropriate size and also made hydrophobic for efficient flotation.In this paper, we show that inkjet-printed newsprint can be satisfactorily deinked via chemistry based on our near-neutral HPES deinking chemistry, described previously [2]. Two kinds of chemicals are used; the “E” in HPES is ethoxylated fatty alcohol, which interacts with the ink and fibers, separates them and prevents the ink from reattaching, while aggregating small ink particles into larger ones. The “S” in HPES is a small amount of an ionic surfactant added into the flotation cell, which facilitates the creation of bubbles which carry particles to the top where they can be skimmed off with the froth, leaving the clean pulp fibers to be recovered. We studied the effect of pH, collecting and clarifying agents, water hardness, chemical loading, and bleaching chemistry on filtrate darkening. In particular, we have found that the color shade and brightness of the deinked pulp and the process water can be significantly enhanced with the addition of a suitable collector or flocculating agent, in this case aluminum sulfate.

ObjectivesWarfarin is the most commonly used oral anticoagulant in the treatment and prevention of many thrombotic disorders. However, warfarin’s narrow therapeutic index and substantial interindividual variation make its dosing notoriously...

In the recent years, thermal ink jet (bubble jet) has emerged to become a fast growing printing technology with market applications first aimed at the low end, high quality and color workstation printers. The break-through in this ink jet technology came in the areas of low cost/high volume manufacture using semiconductor thin-film processing, improved apparent reliability and the ability of high quality printing on wide range of office papers. Although the print head technology appears simple and compact, the underlining thin-film structures, micro fluid channels and drop generation process are by no mean straight-forward. In fact, the ink chemistry, the material integrity and the device physics are closely coupled to provide the proper functionality of the print engine. Hence optimization of the technology can only be achieved through complete device integration. In this paper, the basic implementations of the thermal ink jet technology is presented. The physics of bubble/drop formation process is described using results obtained from our experimental studies. Different failure modes of the electro-thermal drop generator (in particular, the thin-film resistive heater) are discussed. Results can be extrapolated to obtain a basic understanding in the requirements of the ink media and the material structure. Based on the current knowledge of this printing method, projections of the technology limitations in practical implementations can be made to support a view that thermal ink jet will become the dominant low end printing technology in the near future.

The main limitations of the therapeutic effectiveness of tizanidine hydrochloride (TNZ) are its low bioavailability due to its tendency to undergo first-pass metabolism and short biological half-life. These factors make it an ideal candidate for formulating orally disintegrating films. The present study was aimed to prepare nanoparticles of tizanidine hydrochloride using biodegradable polymers and loading them on orodispersible films to obtain a sustained release dissolution profile with improved permeability and further study the cytotoxicity on A549 lung carcinoma cells, MCF7 breast cancer cells, and HOP 92 non-small lung adenocarcinoma cells. The fast-dissolving film of TNZ HCl was prepared by the solvent-casting method and characterized using scanning electron microscopy, FTIR, and XRD, and evaluated for critical quality attributes for this type of dosage form such as disintegration time, tensile strength, drug content, dissolution, and ex vivo permeability. In vitro cytotoxicity studies were also conducted on cancer cell lines to confirm the cytotoxic effect. The polymeric matrix containing the drug provided a rapid disintegration time varying between 7±2 and 30±2 seconds, adequate tensile strength between 1.4 and 11.25 N/mm2, and improved permeability through porcine buccal mucosa when compared to the reference product. A study of the cytotoxic effect on the MCF-7 breast cancer cells and A549 lung carcinoma cells revealed that tizanidine hydrochloride nanoparticles at 2.3 mg/film exhibited an IC50 value of 65.1 % cytotoxicity on MCF-7, approximately 100% on HOP92, and 83.5 % on A549 lung carcinoma cells, thus paving the way for a new paradigm of research for a cytotoxic study on MCF-7, HOP92, and A549 cell lines using the subject drug model prepared as oral films or biodegradable nanoparticles in oral films for site-specific targeting.

Interactions of ink colourants with chemically modified paper surfaces concerning inkjet print improvement

Ink-jet printing is a cost-effective technology that has had varied applications recently. The technology was applied here to an important microbiological procedure, minimum inhibitory concentration (MIC) determination. MIC evaluations were conducted by printing varying concentrations of the antibiotics, ampicillin or tetracycline, onto agar-coated glass slides then printing an even film of known bacterial density of Lactobacillus acidophilus onto the antibioticimprinted slide. Results obtained were validated with a broth microdilution technique. The MICs for ampicillin and tetracycline obtained were two-fold higher than those determined by the conventional technique.

Thermal inkjet printing of thin-film electrolytes and buffering layers for solid oxide fuel cells with improved performance

An amperometric glucose biosensor prototype fabricated by thermal inkjet printing

5 - Digital image design and creation of printed images on textile fabrics

PurposeThe use of two-dimensional (2D) printing technologies of drugs on orodispersible films (ODF) can promote dose individualization and facilitate drug delivery in vulnerable patients, including children. We investigated midazolam pharmacokinetics after the administration of 2D-printed ODF.MethodsMidazolam doses of 0.03 and 3 mg were printed on an ODF using a 2D drug printer. We investigated the bioavailability of the two midazolam doses with ODF swallowed immediately (ODF-IS) or delayed after 2 min (ODF-DS) by comparing their pharmacokinetics with intravenous and oral midazolam solution in 12 healthy volunteers.ResultsThe relative bioavailability of ODF-IS 0.03 mg was 102% (90% confidence interval: 89.4–116) compared to oral solution and for 3 mg 101% (86.8–116). Cmax of ODF-IS 0.03 mg was 95.5% (83.2–110) compared to oral solution and 94.3% (78.2–114) after 3 mg. Absolute bioavailability of ODF-IS 0.03 mg was 24.9% (21.2–29.2) and for 3 mg 28.1% (23.4–33.8) (oral solution: 0.03 mg: 24.4% (22.0–27.1); 3 mg: 28.0% (25.0–31.2)). Absolute bioavailability of ODF-DS was significantly larger than for ODF-IS (0.03 mg: 61.4%; 3 mg: 44.1%; both p < 0.0001).ConclusionThis trial demonstrates the tolerability and unchanged bioavailability of midazolam printed on ODF over a 100-fold dose range, proving the suitability of ODF for dose individualization. Midazolam ODF-IS AUC0–∞ in both doses was bioequivalent to the administration of an oral solution. However, Cmax of the therapeutic dose of ODF-IS missed bioequivalence by a clinically not relevant extent. Prolonged mucosal exposure increased bioavailability. (Trial Registration EudraCT: 2020–003984-24, August 10, 2020).

Heparin anticoagulant therapy for thromboembolic disorders during pregnancy is problematic due to unexpected adverse bleeding. To avoid bleeding, we have used a less-intensive anticoagulation protocol of unfractionated heparin (UFH). The protocol had a therapeutic activated partial thromboplastin time (APTT) ratio of 1.5-2.0 with the control value, a UFH dose of ≤ 30,000U/day, and an antithrombin (AT) activity target of ≥ 70%. In the present study, we evaluated this protocol using an anti-Xa assay. We collected UFH-treated plasma samples from ten consecutive pregnant Japanese patients with current or previous thromboembolic disorders. Seven patients remained in the therapeutic APTT ratio range (heparin-sensitive [HS] group). The other three patients had difficulty remaining within the therapeutic range (heparin-resistant [HR] group). In the HR group, two had AT deficiency and one had congenital absence of the inferior vena cava. Of the HS and HR samples, 73% and 31%, respectively, were within the therapeutic anti-Xa activity range 0.3-0.7U/mL, indicating difficulty for the HR group to remain within the therapeutic range. Neither major bleeding nor symptomatic thromboembolic episodes occurred in either group. These findings suggest that the less-intensive anticoagulation protocol is permissive and may be beneficial in the HS group.