Crystalline nanoxylan from hot water extracted wood xylan at multi-length scale: Molecular assembly from nanocluster hydrocolloids to submicron spheroids.

As a contribution to expand accessibility in the territory of bio-based nanomaterials, we demonstrate a novel material strategy to convert amorphous xylan preserved in wood biomass to hierarchical assemblies of crystalline nanoxylan on a multi-length scale. By reducing the end group in pressurized hot water extracted (PHWE) xylan to primary alcohol as a xylitol form with borohydride reduction, the endwise-peeling depolymerization is effectively impeded in the alkali-catalyzed hydrolytic cleavage of side substitutions in xylan. Nanoprecipitation by a gradual pH decrease resulted in a stable hydrocolloid dispersion in the form of worm-like nanoclusters assembled with primary crystallites, owing to the self-assembly of debranched xylan driven by strong intra- and inter-chain H-bonds. With evaporation-induced self-assembly, we can further construct the hydrocolloids as dry submicron spheroids of crystalline nanoxylan (CNX) with a high average elastic modulus of 47-83 GPa. Taking the advantage that the chain length and homogeneity of PHWE-xylan can be tailored, a structure-performance correlation was established between the structural order in CNX and the phosphorescent emission of this crystalline biopolymer. Rigid clusterization and high crystallinity that are constructed by strong intra- and inter-molecule interactions within the nanoxylan effectively restrict the molecular motion, thereby promoting the emission of ultralong organic phosphorescence.

Gastric acid challenge of lithium disilicate-reinforced glass-ceramics and zirconia-reinforced lithium silicate glass-ceramic after polishing and glazing-impact on surface properties.

OBJECTIVES: To investigate the impact of simulated gastric acid on the surface properties of lithium disilicate-reinforced glass-ceramics and zirconia-reinforced lithium silicate glass-ceramic after certain polishing and glazing procedures. MATERIALS AND METHODS: Four different types of square-shaped specimens (10 × 10 × 2 mm3, n = 13) were manufactured: lithium disilicate-reinforced glass-ceramic milled and polished (LDS-P); milled, polished, and glazed (LDS-PG); milled, glazed, and no polishing (LDS-G); and milled and polished zirconia-reinforced lithium silicate glass-ceramic (ZR-LS). Specimens were immersed in hydrochloride acid (HCl 0.06 M, pH 1.2) to simulate gastric acid irritation and stored in the acid for 96 h in 37 °C. Specimen weight, surface gloss, Vickers surface microhardness and surface roughness (Ra, Rq, with optical profilometer), and surface roughness on nanometer level (Sq, Sal, Sq/Sal, Sdr, Sds with atomic force microscope) were measured before and after the acid immersion. RESULTS: ZR-LS specimens lost significantly more weight after acid immersion (p = 0.001), also surface microhardness of ZR-LS was significantly reduced (p = 0.001). LDS-G and LDS-PG showed significantly lower surface roughness (Sa, Sq) values compared to LDS-P before (p ≤ 0.99) and after (p ≤ 0.99) acid immersion and ZR-LS after acid immersion (p ≤ 0.99). CONCLUSIONS: Gastric acid challenge affects the surface properties of lithium disilicate-reinforced glass-ceramic and zirconia-reinforced lithium silicate glass-ceramic. Glazing layer provides lower surface roughness, and the glazed surface tends to smoothen after the gastric acid challenge. CLINICAL RELEVANCE: Surface finish of lithium disilicate-reinforced glass-ceramic and zirconia-reinforced lithium silicate glass-ceramic has a clear impact on material's surface properties. Gastric acidic challenge changes surface properties but glazing seems to function as a protective barrier. Nevertheless, also glazing tends to smoothen after heavy gastric acid challenge. Glazing can be highly recommended to all glass-ceramic restorations but especially in patients with gastroesophageal reflux disease (GERD) and eating disorders like bulimia nervosa.

Aqueous Processable One-Dimensional Polypyrrole Nanostructured by Lignocellulose Nanofibril: A Conductive Interfacing Biomaterial.

One-dimensional (1D) nanomaterials of conductive polypyrrole (PPy) are competitive biomaterials for constructing bioelectronics to interface with biological systems. Synergistic synthesis using lignocellulose nanofibrils (LCNF) as a structural template in chemical oxidation of pyrrole with Fe(III) ions facilitates surface-confined polymerization of pyrrole on the nanofibril surface within a submicrometer- and micrometer-scale fibril length. It yields a core-shell nanocomposite of PPy@LCNF, wherein the surface of each individual fibril is coated with a thin nanoscale layer of PPy. A highly positive surface charge originating from protonated PPy gives this 1D nanomaterial a durable aqueous dispersity. The fibril-fibril entanglement in the PPy@LCNFs facilely supported versatile downstream processing, e.g., spray thin-coating on glass, flexible membranes with robust mechanics, or three-dimensional cryogels. A high electrical conductivity in the magnitude of several to 12 S·cm-1 was confirmed for the solid-form PPy@LCNFs. The PPy@LCNFs are electroactive and show potential cycling capacity, encompassing a large capacitance. Dynamic control of the doping/undoping process by applying an electric field combines electronic and ionic conductivity through the PPy@LCNFs. The low cytotoxicity of the material is confirmed in noncontact cell culture of human dermal fibroblasts. This study underpins the promises for this nanocomposite PPy@LCNF as a smart platform nanomaterial in constructing interfacing bioelectronics.

Template-Directed Polymerization of Binary Acrylate Monomers on Surface-Activated Lignin Nanoparticles in Toughening of Bio-Latex Films.

Fabricating bio-latex colloids with core-shell nanostructure is an effective method for obtaining films with enhanced mechanical characteristics. Nano-sized lignin is rising as a class of sustainable nanomaterials that can be incorporated into latex colloids. Fundamental knowledge of the correlation between surface chemistry of lignin nanoparticles (LNPs) and integration efficiency in latex colloids and from it thermally processed latex films are scarce. Here, an approach to integrate self-assembled nanospheres of allylated lignin as the surface-activated cores in a seeded free-radical emulsion copolymerization of butyl acrylate and methyl methacrylate is proposed. The interfacial-modulating function on allylated LNPs regulates the emulsion polymerization and it successfully produces a multi-energy dissipative latex film structure containing a lignin-dominated core (16% dry weight basis). At an optimized allyl-terminated surface functionality of 1.04 mmol g-1 , the LNPs-integrated latex film exhibits extremely high toughness value above 57.7 MJ m-3 . With multiple morphological and microstructural characterizations, the well-ordered packing of latex colloids under the nanoconfinement of LNPs in the latex films is revealed. It is concluded that the surface chemistry metrics of colloidal cores in terms of the abundance of polymerization-modulating anchors and their accessibility have a delicate control over the structural evolution of core-shell latex colloids.

Physicochemical and biological characterization of silica-coated alumina particles.

OBJECTIVES: A tribochemical silica-coating (TSC) method has been developed to improve the adhesion of dental resin composites to various substrates. The method utilizes airborne-particle abrasion using particles having a silica surface and an alumina core. The impact of the TSC method has been extensively studied but less attention has been paid to the characterization of the silica-modified alumina particles. Due to the role of silicate ions in cell biology, e.g. osteoblast function and bone mineralization, silica-modified alumina particles could also be potentially used as a biomaterial in scaffolds of tissue regeneration. Thus, we carried out detailed physicochemical characterization of the silica-modified alumina particles. METHODS: Silica-modified alumina particles (Rocatec, 3 M-ESPE) of an average particle size of 30 µm were studied for the phase composition, spectroscopic properties, surface morphology, dissolution, and the capability to modify the pH of an immersion solution. The control material was alumina without silica modification. Pre-osteoblastic MC3T3-E1 cells were used to assess cell viability in the presence of the particles. Cell viability was tested at 1, 3, 7 and 10 days of culture with various particle quantities. Multivariate ANOVA was used for statistical analyses. RESULTS: Minor quantities of silica enrichment was verified on the surface of alumina particles and the silica did not evenly cover the alumina surface. In the dissolution test, no change in the pH of the immersion solution was observed in the presence of the particles. Minor quantities of silicate ions were dissolved from the particles to the cell culture medium but no major differences were observed in the viability of pre-osteoblastic cells, whether the cells were cultured with silica-modified or plain alumina particles. SIGNIFICANCE: Characterization of silica-modified alumina particles demonstrated differences in the particle surface structure compared to control alumina. Dissolution of silica layer in Tris buffer or SBF solution varied from that of cell culture medium: minor quantities of dissolved Si were observed in cell culture test medium. The cell viability test did not shown significant differences between control alumina and its silica-modified counterpart.

Water-soluble polysaccharides promoting production of redispersible nanocellulose.

To date, the energy-intensive production and high-water content severely limits nanocellulose applications on a large scale off-site. In this study, adding water-soluble polysaccharides (PS) to achieve an integrated process of water-redispersible nanocellulose production was well established. The addition of PS, in particular carboxymethylated-galactoglucomannan (cm-GGM), facilitates fibre fibrillation enabling homogenization at a higher solid content at 1.5 wt% compared with around 0.4 wt% for neat fibre. More importantly, the addition of cm-GGM saved 73 % energy in comparison without PS addition. Good water redispersibility of thus-prepared nanocellulose was validated in viewpoints of size distribution, morphology, viscosity and film properties as compared with neat nanocellulose. The tensile strength and optical transmittance of nanocellulose films increased to 116 MPa and 77 % compared to those without PS addition of 62 MPa and 74 %, respectively. Collectively, this study provides a new avenue for large-volume production of redispersible nanocellulose at a high solid content with less energy-consumption.

Role of Surface Coverage and Film Quality of the TiO2 Electron Selective Layer for Optimal Hole-Blocking Properties.

Titanium dioxide (TiO2) is a commonly used electron selective layer in thin-film solar cells. The energy levels of TiO2 align well with those of most light-absorbing materials and facilitate extracting electrons while blocking the extraction of holes. In a device, this separates charge carriers and reduces recombination. In this study, we have evaluated the hole-blocking behavior of TiO2 compact layers using charge extraction by linearly increasing voltage in a metal-insulator-semiconductor structure (MIS-CELIV). This hole-blocking property was characterized as surface recombination velocity (S R) for holes at the interface between a semiconducting polymer and TiO2 layer. TiO2 layers of different thicknesses were prepared by sol-gel dip coating on two transparent conductive oxide substrates with different roughnesses. Surface coverage and film quality on both substrates were characterized using X-ray photoelectron spectroscopy and atomic force microscopy, along with its conductive imaging mode. Thicker TiO2 coatings provided better surface coverage, leading to reduced S R, unless the layers were otherwise defective. We found S R to be a more sensitive indicator of the overall film quality, as varying S R values were still observed among the films that looked similar in their characteristics via other methods.

Structural and elemental characterization of glass and ceramic particles for bone surgery.

OBJECTIVE: Clinically used bioceramics have been characterized previously with different kinds of methods and comparison of results have proven to be difficult due to varieties of the material properties of interest. Therefore, in this study we compared clinically commonly used bioceramics of hydroxyapatite and carbonate apatite, two bioactive glasses 45S5 and S53P4, and alumina with respect of properties which according to the present knowledge are significant for bone biology. METHODS: Physicochemical properties of the materials were characterized by various methods. Attenuated Total Reflectance Fourier Transform Infrared (ATR-FTIR) was used to analyze the material vibrational features. X-ray Power Diffraction (XRD) was used to characterize the material crystal structure and scanning electron microscopy-energy-dispersive x-ray analysis (SEM-EDXA) was used to evaluate the morphology and size of the materials and to calculate their oxide content. The dissolution behavior of the materials, ion release and pH changes in Tris buffer in a continuous flow-through reaction for 24-hours were determined. The change of the surface of the bioactive glasses by interfacial reaction during the Tris immersion was examined and the thickness of the surface reaction layer of the materials was studied. RESULTS: SEM examination showed that the particle morphology of BG 45S5, BG S53P4 and alumina particle's surface was smooth. The surface of HAP was porous, but also CAP showed some surface porosity. An increase in the pH of the immersion solution was observed especially for BG 45S5 and BG S53P4. HAP, CAP and alumina caused only a minor increase in pH. BGs 45S5 and S53P4 showed a rapid initial release of sodium and calcium ions, followed by the release of silicon species. Minor release of sodium ions was registered for HAP, CAP and alumina. Calcium ion release was low but constant over the experimental time while only a minor initial dissolution was measured for HAP. SIGNIFICANCE: The in vitro study showed differences in the materials' properties, which are considered to be important for biological suitability and in clinical applications, such as materials tomography, ion release and pH changes.

Structural and Functional Dynamics of Staphylococcus aureus Biofilms and Biofilm Matrix Proteins on Different Clinical Materials.

Medical device-associated staphylococcal infections are a common and challenging problem. However, detailed knowledge of staphylococcal biofilm dynamics on clinically relevant surfaces is still limited. In the present study, biofilm formation of the Staphylococcus aureus ATCC 25923 strain was studied on clinically relevant materials-borosilicate glass, plexiglass, hydroxyapatite, titanium and polystyrene-at 18, 42 and 66 h. Materials with the highest surface roughness and porosity (hydroxyapatite and plexiglass) did not promote biofilm formation as efficiently as some other selected materials. Matrix-associated poly-N-acetyl-ß-(1-6)-glucosamine (PNAG) was considered important in young (18 h) biofilms, whereas proteins appeared to play a more important role at later stages of biofilm development. A total of 460 proteins were identified from biofilm matrices formed on the indicated materials and time points-from which, 66 proteins were proposed to form the core surfaceome. At 18 h, the appearance of several r-proteins and glycolytic adhesive moonlighters, possibly via an autolysin (AtlA)-mediated release, was demonstrated in all materials, whereas classical surface adhesins, resistance- and virulence-associated proteins displayed greater variation in their abundances depending on the used material. Hydroxyapatite-associated biofilms were more susceptible to antibiotics than biofilms formed on titanium, but no clear correlation between the tolerance and biofilm age was observed. Thus, other factors, possibly the adhesive moonlighters, could have contributed to the observed chemotolerant phenotype. In addition, a protein-dependent matrix network was observed to be already well-established at the 18 h time point. To the best of our knowledge, this is among the first studies shedding light into matrix-associated surfaceomes of S. aureus biofilms grown on different clinically relevant materials and at different time points.

Immobilization of proteolytic enzymes on replica-molded thiol-ene micropillar reactors via thiol-gold interaction.

We introduce rapid replica molding of ordered, high-aspect-ratio, thiol-ene micropillar arrays for implementation of microfluidic immobilized enzyme reactors (IMERs). By exploiting the abundance of free surface thiols of off-stoichiometric thiol-ene compositions, we were able to functionalize the native thiol-ene micropillars with gold nanoparticles (GNPs) and these with proteolytic α-chymotrypsin (CHT) via thiol-gold interaction. The micropillar arrays were replicated via PDMS soft lithography, which facilitated thiol-ene curing without the photoinitiators, and thus straightforward bonding and good control over the surface chemistry (number of free surface thiols). The specificity of thiol-gold interaction was demonstrated over allyl-rich thiol-ene surfaces and the robustness of the CHT-IMERs at different flow rates and reaction temperatures using bradykinin hydrolysis as the model reaction. The product conversion rate was shown to increase as a function of decreasing flow rate (increasing residence time) and upon heating of the IMER to physiological temperature. Owing to the effective enzyme immobilization onto the micropillar array by GNPs, no further purification of the reaction solution was required prior to mass spectrometric detection of the bradykinin hydrolysis products and no clogging problems, commonly associated with conventional capillary packings, were observed. The activity of the IMER remained stable for at least 1.5 h (continuous use), suggesting that the developed protocol may provide a robust, new approach to implementation of IMER technology for proteomics research. Graphical abstract.

Human dermal fibroblast proliferation controlled by surface roughness of two-component nanostructured latex polymer coatings.

In this study hierarchically-structured latex polymer coatings and self-supporting films were characterised and their suitability for cell growth studies was tested with Human Dermal Fibroblasts (HDF). Latex can be coated or printed on rigid or flexible substrates thus enabling high-throughput fabrication. Here, coverslip glass substrates were coated with blends of two different aqueous latex dispersions: hydrophobic polystyrene (PS) and hydrophilic carboxylated acrylonitrile butadiene styrene (ABS). The nanostructured morphology and topography of the latex films was controlled by varying the mixing ratio of the components in the latex blend. Thin latex-coatings retain high transparency on glass allowing optical and high resolution imaging of cell growth and morphology. Compared to coverslip glass surfaces and commercial well-plates HDF cell growth was enhanced up to 150-250 % on latex surfaces with specific nanostructure. Growth rates were correlated with selected roughness parameters such as effective surface area (Sq), RMS-roughness (Sdr) and correlation length (Scl37). High-resolution confocal microscopy clearly indicated less actin stress-fibre development in cells on the latex surface compared to coverslip glass. The results show that surface nanotopography can, by itself, passively modulate HDF cell proliferation and cytoskeletal architecture.

Dissolution and mineralization characterization of bioactive glass ceramic containing endodontic sealer Guttaflow Bioseal.

Aim of the study was to evaluate apatite forming ability and ion dissolution of bioactive glass-ceramic (BGC) particles from novel polydimethylsiloxane (PDMS) based endodontic sealer Guttaflow Bioseal. Firstly, water sorption and solubility were determined for Guttaflow 2 and Guttaflow Bioseal (GB), the latter containing BGC filler particles. Mineral precipitations in simulated body fluid (SBF) were observed with SEM/EDX. Ion-release from the sealer was determined with inductively coupled plasma optical emission spectrometry (ICP-OES) in Tris-buffer solution. Change in pH was also measured. The obtained data was statistically analyzed with Tukey's HSD test (p<0.05). GB exhibited significantly higher water sorption and solubility in comparison with Guttaflow 2. Surface structure exposed particles of BGC in the PDMS matrix. The BGC particles (size of 20-40 µm) indicated to consist of CaO-SiO2-Na2O-ZrO2-P2O5. Morphologically spherical Ca/P precipitation formed after 3 days in the SBF on the sealer surface. Ca/P ratio of the precipitation ranged in 1.20-1.65 indicating transformation to hydroxyapatite (HA). The pH of the immersion solution rose gradually.

Gold nanoparticle printed coverslips to facilitate fluorescence-TEM correlative microscopy.

Correlative light and electron microscopy (CLEM) allows combining the advantages of fluorescence microscopy and electron microscopy for cell imaging. Rare phenomenon expressing cells can be studied by specifically tagged fluorophores with fluorescence microscopy. Subsequently, cells can be fixed and ultra-structural details can be studied with transmission electron microscopy (TEM) at a higher resolution. However, precise landmarks are necessary to track the same cell throughout the CLEM process. In this technical report, we present a high contrast inkjet-printed gold nanoparticle patterns over commercial glass coverslip to facilitate cell tracking with correlative microscopy. High contrast and strong reflection from nano gold pattern can be used as a fixed landmark for cell identification with fluorescence microscopy. Nano gold printed letters over coverslips are visible in resin blocks, which can be further used to identify the cell of interest for performing sectioning of embedded cell blocks for TEM.

Tailored Approaches in Drug Development and Diagnostics: From Molecular Design to Biological Model Systems.

Approaches to increase the efficiency in developing drugs and diagnostics tools, including new drug delivery and diagnostic technologies, are needed for improved diagnosis and treatment of major diseases and health problems such as cancer, inflammatory diseases, chronic wounds, and antibiotic resistance. Development within several areas of research ranging from computational sciences, material sciences, bioengineering to biomedical sciences and bioimaging is needed to realize innovative drug development and diagnostic (DDD) approaches. Here, an overview of recent progresses within key areas that can provide customizable solutions to improve processes and the approaches taken within DDD is provided. Due to the broadness of the area, unfortunately all relevant aspects such as pharmacokinetics of bioactive molecules and delivery systems cannot be covered. Tailored approaches within (i) bioinformatics and computer-aided drug design, (ii) nanotechnology, (iii) novel materials and technologies for drug delivery and diagnostic systems, and (iv) disease models to predict safety and efficacy of medicines under development are focused on. Current developments and challenges ahead are discussed. The broad scope reflects the multidisciplinary nature of the field of DDD and aims to highlight the convergence of biological, pharmaceutical, and medical disciplines needed to meet the societal challenges of the 21st century.

Bioactive glass combined with bisphosphonates provides protection against biofilms formed by the periodontal pathogen Aggregatibacter actinomycetemcomitans.

Biofilms play a pivotal role in the progression of periodontitis and they can be treated with antiseptics (i.e. chlorhexidine) or antibiotics, but these therapeutic alternatives are unable of ameliorating periodontal alveolar bone loss, which has been, on the other hand, successfully treated with bone-preserving agents. The improved bone formation achieved in animal models by the combination of two such agents: bioactive glass (BAG) and bisphosphonates has attracted the interest for further exploring dental applications. However, the antimicrobial effects that may result from combining them have not been yet investigated. Here, our aim was to explore the anti-biofilm effects that could result from combining BAG with bisphosphonates, particularly in a dental biofilm model. The experiments were performed with an oral cavity single-specie (Aggregatibacter actinomycetemcomitans) biofilm assay, which was optimized in this contribution. Risedronate displayed an intrinsic anti-biofilm effect, and all bisphosphonates, except clodronate, reduced biofilm formation when combined with BAG. In particular, the anti-biofilm activity of risedronate was significantly increased by the combination with BAG. Since it has been proposed that some of the antimicrobial effects of BAG are caused by local pH changes, studies of pH variations were performed to gain a mechanistic understanding. However, the observed anti-biofilm effects could not be explained with lowered pHs. Overall, these results do provide further support for the promising use of bisphosphonate-BAG combinations in dental applications. These findings are particularly relevant for patients undergoing cancer chemotherapy, or osteoporotic patients, which are known to be more vulnerable to periodontitis. In such cases, bisphosphonate treatment could play a double positive effect: local treatment of periodontitis (in combination with BAG) and systemic treatment of osteoporosis, prevention of hypercalcemia and metastases.

Protein and bacterial interactions with nanostructured polymer coatings.

Adsorption of proteins and adhesion of bacteria to a surface is affected by chemical and physical interactions. In this study, polymer coatings and their ability to adsorb avidin and Staphylococcus aureus were investigated. The surface chemistry and topography of the polymer coatings was modified by changing the weight ratio of the hydrophobic polystyrene (PS) and the hydrophilic acrylonitrile butadiene styrene (ABS) components in the polymer blend. Avidin adsorbed less to the ABS phase compared with the PS phase. The side-on orientation of avidin on the ABS surface, however, resulted in a higher specific binding of biotinylated bovine serum albumin. Steric effects and hydrophobic protein-surface interactions decreased the activity of avidin on the PS phase. The increased hydrophobicity and roughness of the polymer coatings enhanced the adhesion of S. aureus. The avidin-coated latex surface with 55% relative surface coverage of the PS phase showed anti-microbial behavior.

Cellulose nanocrystals prepared via formic acid hydrolysis followed by TEMPO-mediated oxidation.

Cellulose nanocrystals (CNCs) as a renewable and biodegradable nanomaterial have wide application value. In this work, CNCs were extracted from bleached chemical pulp using two stages of isolation (i.e. formic acid (FA) hydrolysis and 2,2,6,6-tetramethyl-piperidine-1-oxyl (TEMPO) mediated oxidation) under mild conditions. In the first stage, FA was used to remove hemicellulose, swell cellulose fibers, and release CNCs. The FA could be readily recovered and reused. In the second stage, the CNCs isolated by FA were further modified by TEMPO-mediated oxidation to increase the surface charge of CNCs. It was found that the modified CNCs with more ordered crystal structure and higher surface charge had better redispersibility and higher viscosity in aqueous phase. Therefore, the modified CNCs could be more effective when used as rheology modifier in the fields of water based coating, paint, food etc.

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.

Fabrication of drug-loaded edible carrier substrates from nanosuspensions by flexographic printing.

The main goal of the current work was to investigate the possible use of flexographic printing for the conversion of nanosuspensions into solid dosage forms. Aqueous nanosuspensions of indomethacin (IND) and itraconazole (ITR) with Poloxamer 407 as the stabilizer agent were prepared by wet ball-milling. The nanosuspensions were flexographically printed on three different substrates, including two commercially available edible substrates. The printed formulations were characterized with X-ray diffractometry (XRD) and scanning electron microscopy (SEM). In addition, dissolution studies for the printed IND and ITR formulations were conducted. The mean particle size of milled nanosuspensions of IND and ITR was 422.6 ± 7.7 nm and 698.1 ± 14.0 nm, respectively. The SEM imaging showed even distribution of nanosuspensions on the substrates after printing without any evident agglomeration. The printed formulations contained drug at least partially in crystalline form. The drug dissolution rate from the prepared formulations was improved compared to the pure drug. The drug release from the preparations on edible substrates was slightly slower due to the incorporation of the drug particles into the substrate matrix. In conclusion, the results indicated that flexographic printing can be considered as a promising fabrication method of solid nanoparticulate systems with enhanced dissolution behavior.

Hyperspectral imaging in quality control of inkjet printed personalised dosage forms.

The aim of the study was to investigate applicability of near infra-red (NIR) hyperspectral imaging technique in quality control of printed personalised dosage forms. Inkjet printing technology was utilized to fabricate escalating doses of an active pharmaceutical ingredient (API). A solution containing anhydrous theophylline as the model drug was developed as a printable formulation. Single units solid dosage forms (SDFs) were prepared by jetting the solution onto 1 cm × 1 cm areas on carrier substrate with multiple printing passes. It was found that the number of printing passes was in excellent correlation (R(2)=0.9994) with the amount of the dispensed drug (µg cm(-2)) based on the UV calibration plot. The API dose escalation was approximately 7.5 µg cm(-2) for each printing pass concluding that inkjet printing technology can optimally provide solutions to accurate deposition of active substances with a potential for personalized dosing. Principal component analysis (PCA) was carried out in order to visualize the trends in the hyperspectral data. Subsequently, a quantitative partial least squares (PLS) regression model was created. NIR hyperspectral imaging proved (R(2)=0.9767) to be a reliable, rapid and non-destructive method to optimize quality control of these planar printed dosage forms.