Petri Ihalainen

Inkjet printing of drug substances and use of porous substrates‐towards individualized dosing

Medicines are most often oral solid dosage forms made into tablets or capsules, and there is little room for individualized doses. The drug substance and additives are processed through multiple production phases, including complex powder handling steps. In drug manufacturing, the control of the solid-state properties of active pharmaceutical ingredient (API) is essential and it offers opportunities for enhancement of drug delivery systems. In this context, inkjet printing technologies have emerged over the last decades in pharmaceutical and biological applications and offer solutions for controlling material and product characteristics with high precision. Here we report the concept of conventional inkjet printing technology to produce printable pharmaceutical dosage forms on porous substrates. Data are shown to demonstrate inkjet printing of APIs into paper substrates, and how the model drug substances (paracetamol, theophylline, and caffeine) are penetrating the porous substrates used. The method enables controlling not only the deposition but also the crystallization of the drug substances. We anticipate that the inkjet printing approach has immense potential in making sophisticated drug delivery systems by use of porous substrates in the future. For example, it may offer new perspectives for solving problems around poorly soluble drugs and dosing low-dose medicines accurately. Furthermore, with the advent of genetic mapping of humans, controlled inkjet dosing can bring solutions to fabricate on-demand individualized medicines for patients.

Tailoring controlled-release oral dosage forms by combining inkjet and flexographic printing techniques.

We combined conventional inkjet printing technology with flexographic printing to fabricate drug delivery systems with accurate doses and tailored drug release. Riboflavin sodium phosphate (RSP) and propranolol hydrochloride (PH) were used as water-soluble model drugs. Three different paper substrates: A (uncoated woodfree paper), B (triple-coated inkjet paper) and C (double-coated sheet fed offset paper) were used as porous model carriers for drug delivery. Active pharmaceutical ingredient (API) containing solutions were printed onto 1 cm × 1 cm substrate areas using an inkjet printer. The printed APIs were coated with water insoluble polymeric films of different thickness using flexographic printing. All substrates were characterized with respect to wettability, surface roughness, air permeability, and cell toxicity. In addition, content uniformity and release profiles of the produced solid dosage forms before and after coating were studied. The substrates were nontoxic for the human cell line assayed. Substrate B was smoothest and least porous. The properties of substrates B and C were similar, whereas those of substrate A differed significantly from those of B, C. The release kinetics of both printed APIs was slowest from substrate B before and after coating with the water insoluble polymer film, following by substrate C, whereas substrate A showed the fastest release. The release rate decreased with increasing polymer coating film thickness. The printed solid dosage forms showed excellent content uniformity. So, combining the two printing technologies allowed fabricating controlled-release oral dosage forms that are challenging to produce using a single technique. The approach opens up new perspectives in the manufacture of flexible doses and tailored drug-delivery systems.

Inkjet-printed gold electrodes on paper: characterization and functionalization.

Gold nanoparticles were synthesized and inkjet-printed on a paper substrate and IR-sintered to produce conductive electrodes. The electrodes were further functionalised by using self-assembled octadecanethiol monolayers (SAMs). The effect of sintering, print quality, and SAM formation were examined by topographical, chemical and electrical methods. With optimised printing parameters, a volume resistivity of ~1.6 × 10(-7) Ω m was attained by a single print layer.

Biocomposites of Nanofibrillated Cellulose, Polypyrrole, and Silver Nanoparticles with Electroconductive and Antimicrobial Properties

In this work, flexible and free-standing composite films of nanofibrillated cellulose/polypyrrole (NFC/PPy) and NFC/PPy-silver nanoparticles (NFC/PPy-Ag) have been synthesized for the first time via in situ one-step chemical polymerization and applied in potential biomedical applications. Incorporation of NFC into PPy significantly improved its film formation ability resulting in composite materials with good mechanical and electrical properties. It is shown that the NFC/PPy-Ag composite films have strong inhibition effect against the growth of Gram-positive bacteria, e.g., Staphylococcus aureus. The electrical conductivity and strong antimicrobial activity makes it possible to use the silver composites in various applications aimed at biomedical treatments and diagnostics. Additionally, we report here the structural and morphological characterization of the composite materials with Fourier-transform infrared spectroscopy, atomic force microscopy, and scanning and transmission electron microscopy techniques.

Printing technologies in fabrication of drug delivery systems.

Introduction: There has been increased activity in the field recently regarding the development and research on various printing techniques in fabrication of dosage forms and drug delivery systems. These technologies may offer benefits and flexibility in manufacturing, potentially paving the way for personalized dosing and tailor-made dosage forms. Areas covered: In this review, the most recent observations and advancements in fabrication of drug delivery systems by utilizing printing technologies are summarized. A general overview of 2D printing techniques is presented including a review of the most recent literature where printing techniques are used in fabrication of drug delivery systems. The future perspectives and possible impacts on formulation strategies, flexible dosing and personalized medication of using printing techniques for fabrication of drug delivery systems are discussed. Expert opinion: It is evident that there is an urgent need to meet the challenges of rapidly growing trend of personalization of medicines through development of flexible drug-manufacturing approaches. In this context, various printing technologies, such as inkjet and flexography, can play an important role. Challenges on different levels exist and include: i) technological development of printers and production lines; ii) printable formulations and carrier substrates; iii) quality control and characterization; and iv) regulatory perspectives.

Biocompatibility of printed paper-based arrays for 2-D cell cultures.

The use of paper-based test platforms in cell culture experiments is demonstrated. The arrays used for two-dimensional cell cultures were prepared by printing patterned structures on a paper substrate using a hydrophobic polydimethylsiloxane (PDMS) ink. The non-printed, PDMS-free areas formed the array for the cell growth experiments. Cell imaging was enabled by using a lipophilic staining agent. A set of coated paper substrates was prepared to study the effect of the physicochemical properties of the substrate (topography, roughness and surface energetics) on cell attachment and growth. The studied paper substrates were found to be cell-repellent or cell-supporting. Cell growth was supported by substrates with a large bearing area, low surface area ratio (Sdr), high total surface free energy and an intermediate electron donor surface energy component. The cells were grown to full confluency within 72 h.

Improvement of dissolution rate of indomethacin by inkjet printing

The aim of this study was to prepare printable inks of the poorly water soluble drug indomethacin (IMC), fabricate printed systems with flexible doses and investigate the effect of ink excipients on the printability, dissolution rate and the solid state properties of the drug. A piezoelectric inkjet printer was used to print 1×1cm(2) squares onto a paper substrate and an impermeable transparency film. l-arginine (ARG) and polyvinylpyrrolidone (PVP) were used as additional formulation excipients. Accurately dosed samples were generated as a result of the ink and droplet formation optimization. Increased dissolution rate was obtained for all formulations. The formulation with IMC and ARG printed on transparency film resulted in a co-amorphous system. The solid state characteristics of the printed drug on porous paper substrates were not possible to determine due to strong interference from the spectra of the carrier substrate. Yet, the samples retained their yellow color after 6months of storage at room temperature and after drying at elevated temperature in a vacuum oven. This suggests that the samples remained either in a dissolved or an amorphous form. Based on the results from this study a formulation guidance for inkjet printing of poorly soluble drugs is also proposed.

Application of Paper-Supported Printed Gold Electrodes for Impedimetric Immunosensor Development

In this article, we report on the formation and mode-of-operation of an affinity biosensor, where alternate layers of biotin/streptavidin/biotinylated-CRP-antigen/anti-CRP antibody are grown on printed gold electrodes on disposable paper-substrates. We have successfully demonstrated and detected the formation of consecutive layers of supra-molecular protein assembly using an electrical (impedimetric) technique. The formation process is also supplemented and verified using conventional surface plasmon resonance (SPR) measurements and surface sensitive characterization techniques, such as X-ray photoelectron spectroscopy (XPS) and atomic force microscopy (AFM). The article provides a possible biosensor development scheme, where—(1) fabrication of paper substrate (2) synthesis of gold nanoparticle inks (3) inkjet printing of gold electrodes on paper (4) formation of the biorecognition layers on the gold electrodes and (5) electrical (impedimetric) analysis of growth—all are coupled together to form a test-structure for a recyclable and inexpensive point-of-care diagnostic platform.

Thermodynamic characterization of Langmuir monolayers of thiolipids: A conceptual analysis

A comprehensive thermodynamic analysis of Langmuir monolayers of two thiolipids has been carried out. Starting from the differentiated integral characteristic state functions for thin films, the consecutive partial derivatives were calculated and arranged to isothermal area derivatives, isobaric temperature derivatives and isoarea pressure derivatives. The obtained surface compressibility, surface expansivity and surface pressure coefficient parameters where then analyzed for the studied monolayers. These parameters appeared to be quite powerful in detecting the extension and sharpness of the characteristic co-operativity of the film-forming substances.

Printing technologies for biomolecule and cell-based applications

Biomolecules, such as enzymes, proteins and other biomacromolecules (polynucleotides, polypeptides, polysaccharides and DNA) that are immobilized on solid surfaces are relevant to many areas of science and technology. These functionalized surfaces have applications in biosensors, chromatography, diagnostic immunoassays, cell culturing, DNA microarrays and other analytical techniques. Printing technologies offer opportunities in this context. The main interests in printing biomolecules are in immobilizing them on surfaces for sensors and catalysts or for controlled delivery of protein-based drugs. Recently, there have been significant developments in the use of inkjet printing for dispensing of proteins, biomacromolecules and cells. This review discusses the use of roll-to-roll and inkjet printing technologies in manufacturing of biomolecule and cell-based applications.