Three-dimensional printing (3DP) has gained popularity among scientists and researchers in every field due to its potential to drastically reduce energy costs for the production of customized products by utilizing less energy-intensive machines as well as minimizing material waste. The 3D printing technology is an additive manufacturing approach that uses material layer-by-layer fabrication to produce the digitally specified 3D model. The use of 3D printing technology in the pharmaceutical sector has the potential to revolutionize research and development by providing a quick and easy means to manufacture personalized one-off batches, each with unique dosages, distinct substances, shapes, and sizes, as well as variable release rates. This overview addresses the concept of 3D printing, its evolution, and its operation, as well as the most popular types of 3D printing processes utilized in the health care industry. It also discusses the application of these cutting-edge technologies to the pharmaceutical industry, advancements in various medical fields and medical equipment, 3D bioprinting, the most recent initiatives to combat COVID-19, regulatory frameworks, and the major challenges that this technology currently faces. In addition, we attempt to provide some futuristic approaches to 3DP applications.
- MeSH
- Printing, Three-Dimensional * MeSH
- Bioprinting methods MeSH
- COVID-19 * MeSH
- Drug Industry MeSH
- Humans MeSH
- Delivery of Health Care MeSH
- SARS-CoV-2 isolation & purification MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
OBJECTIVE: This study aimed to compare the force degradation of intermaxillary elastics (IE) in vitro and in vivo while stretching the IE to a precise diameter. MATERIALS AND METHODS: IE 3/16′′ medium Dentaurum from five different batches of packaging were analyzed. The in vivo study involved 10 volunteers, of which 100 IE were examined. To achieve three times the original diameter of the elastic, the distance between the upper canine and the lower dental arch was measured. Buttons were then placed in the mouth accordingly, and IE and passive aligners were inserted for five sessions of 48 h each. To investigate in vitro, 100 IE were placed in an incubator set at 37°C in a humid environment and stretched three times their diameter. The force of the elastics was measured in both investigations using a force meter at 0, 2, 8, 24, and 48 h. RESULTS: In all patients except one, the three times diameter distance extended from the upper canine to the lower second premolar. The force degradation in vivo at 2, 8, 24, and 48 h was 20.58%, 26.78%, 34.81%, and 38.56% and in vitro was 16.38%, 22.83%, 28.32%, and 30.78%. CONCLUSIONS: The amount of stretching of IE varies for each patient when using standard insertion points. The force of IE decreases exponentially, the force degradation in vivo being higher. The clinician must consider the force decrease when advising the patient of the time interval to change the elastics.
- MeSH
- Dental Stress Analysis MeSH
- Adult MeSH
- Latex * chemistry MeSH
- Humans MeSH
- Stress, Mechanical MeSH
- Young Adult MeSH
- Orthodontic Appliances MeSH
- Orthodontic Appliance Design MeSH
- Materials Testing * MeSH
- Dental Arch MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Young Adult MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Comparative Study MeSH
Many small molecules require derivatization to increase their volatility and to be amenable to gas chromatographic (GC) separation. Derivatization is usually time-consuming, and typical batch-wise procedures increase sample variability. Sequential automation of derivatization via robotic liquid handling enables the overlapping of sample preparation and analysis, maximizing time efficiency and minimizing variability. Herein, a protocol for the fully automated, two-stage derivatization of human blood-based samples in line with GC-[Orbitrap] mass spectrometry (MS)-based metabolomics is described. The protocol delivers a sample-to-sample runtime of 31 min, being suitable for better throughput routine metabolomic analysis. Key features • Direct and rapid methoximation on vial followed by silylation of metabolites in various blood matrices. • Measure ~40 samples per 24 h, identifying > 70 metabolites. • Quantitative reproducibility of routinely measured metabolites with coefficients of variation (CVs) < 30%. • Requires a Thermo ScientificTM TriPlusTM RSH (or comparable) autosampler equipped with incubator/agitator, cooled drawer, and automatic tool change (ATC) station equipped with liquid handling tools. Graphical overview Workflow for profiling metabolites in human blood using automated derivatization.
- Publication type
- Journal Article MeSH
OBJECTIVE: Radiographic assessment of sacroiliac joints (SIJs) according to the modified New York (mNY) criteria is key in the classification of axial spondyloarthritis but has moderate interreader agreement. We aimed to investigate the improvements of the reliability in scoring SIJ radiographs after applying an online real-time iterative calibration (RETIC) module, in addition to a slideshow and video alone. METHODS: Nineteen readers, randomized to 2 groups (A or B), completed 3 calibration steps: (1) review of manuscripts, (2) review of slideshow and video with group A completing RETIC, and (3) re-review of slideshow and video with group B completing RETIC. The RETIC module gave instant feedback on readers' gradings and continued until predefined reliability ([Formula: see text]) targets for mNY positivity/negativity were met. Each step was followed by scoring different batches of 25 radiographs (exercises I to III). Agreement ([Formula: see text]) with an expert radiologist was assessed for mNY positivity/negativity and individual lesions. Improvements by training strategies were tested by linear mixed models. RESULTS: In exercises I, II, and III, mNY [Formula: see text] were 0.61, 0.76, and 0.84, respectively, in group A; and 0.70, 0.68, and 0.86, respectively, in group B (ie, increasing, mainly after RETIC completion). Improvements were observed for grading both mNY positivity/negativity and individual pathologies, both in experienced and, particularly, inexperienced readers. Completion of the RETIC module in addition to the slideshow and video caused a significant [Formula: see text] increase of 0.17 (95% CI 0.07-0.27; P = 0.002) for mNY-positive and mNY-negative grading, whereas completion of the slideshow and video alone did not ([Formula: see text] = 0.00, 95% CI -0.10 to 0.10; P = 0.99). CONCLUSION: Agreement on scoring radiographs according to the mNY criteria significantly improved when adding an online RETIC module, but not by slideshow and video alone.
- MeSH
- Axial Spondyloarthritis * diagnostic imaging MeSH
- Humans MeSH
- Observer Variation * MeSH
- Radiography * methods MeSH
- Reproducibility of Results MeSH
- Sacroiliac Joint * diagnostic imaging MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Randomized Controlled Trial MeSH
Background/Objectives: PET imaging of bacterial infection could potentially provide added benefits for patient care through non-invasive means. [68Ga]Ga-desferrioxamine B-a radiolabelled siderophore-shows specific uptake by human-pathogenic bacteria like Staphylococcus aureus or Pseudomonas aeruginosa and sufficient serum stability for clinical application. In this report, we present data for automated production of [68Ga]Ga-desferrioxamine B on two different cassette-based synthesis modules (Modular-Lab PharmTracer and GRP 3V) utilising commercially obtainable cassettes together with a licensed 68Ge/68Ga radionuclide generator. Methods: Quality control, including the determination of radiochemical purity, as well as a system suitability test, was set up via RP-HPLC on a C18 column. The two described production processes use an acetic acid/acetate buffer system with ascorbic acid as a radical scavenger for radiolabelling, yielding ready-to-use formulations with sufficient activity yield. Results: Batch data analysis demonstrated radiochemical purity of >95% by RP-HPLC combined with ITLC and excellent stability up to 2 h after synthesis. Specifications for routine production were set up and validated with four masterbatches for each synthesis module. Conclusions: Based on this study, an academic clinical trial for imaging of bacterial infection was initiated. Both described synthesis methods enable automated production of [68Ga]Ga-desferrioxamine B in-house with high reproducibility for clinical application.
- Publication type
- Journal Article MeSH
IMUNOR is an oral biotherapeutic drug that had been developed, registered, and approved in 1997 in the Czech Republic and Slovakia. IMUNOR is a dialyzable leukocyte extract (DLE) prepared from swine leukocytes. It is characterized as a mixture of small peptides with molecular weights smaller than 12 kDa and a specific portion of nucleotides. The medical uses of IMUNOR include therapeutic applications within its registered range of indications, primarily for the treatment of immunodeficiencies, allergies, and certain acute or relapsing bacterial infections in adults and children. Despite the long-term clinical application of DLE, with strong evidence of positive therapeutic effects and no serious side effects, a detailed physicochemical specification of this mixture was lacking. We developed several methods for more in-depth physicochemical characterization of IMUNOR, including a spectrophotometric method for quantification of the total protein concentration and total DNA concentration in a mixture, several chromatographic methods for identification of individual components present in significant concentrations in IMUNOR, such as HPLC methods and the Sodium Dodecyl Sulphate Polyacrylamide Gel Electrophoresis method, and characterization of amino acid composition of this mixture. For the investigation of the variability among different batches of IMUNOR, five to nine representative batches from a standard manufacturing process on an industrial scale were utilized. Using the analytical methods, we verified and confirmed the batch-to-batch reproducibility of the biological product IMUNOR.
- Publication type
- Journal Article MeSH
The aim of this study was to compare the microbiological quality of cooked sausages produced with a traditional salt content (2.1%) and reformulated batches with a salt content reduced to 1.7%. The reformulation was tested on two types of comminuted meat products – Špekáčky sausage with a diameter of up to 46 mm or Bologna-type sausages in diameter of 85 mm (Gothaj sausage) or 75 mm (Junior sausage). The total viable count (TVC) increased only slightly during the four-week storage (4 ± 1 °C) of all batches of Špekáčky sausage. Comparing batches 1.7 and 2.1, there is an evident difference in the number of CFU/g, with samples of Špekáčky 1.7 showing numbers of bacteria higher by approximately 1 logarithmic order throughout practically the entire storage period (P = 0.001). The population of lactic acid bacteria (LAB) remained well beneath a value of 5.0 log CFU/g even at the end of the experiment. For Bologna-type sausages, the TVC was either beneath the limit of detection or at its boundary in all samples. LAB were not detected during storage of Bologna-type sausages. The results confirmed that the proportion of salt in cooked sausages can be reduced to 1.7% without negatively affecting the shelf life or safety of the final products.
The bioprinting of high-concentrated collagen bioinks is a promising technology for tissue engineering and regenerative medicine. Collagen is a widely used biomaterial for bioprinting because of its natural abundance in the extracellular matrix of many tissues and its biocompatibility. High-concentrated collagen hydrogels have shown great potential in tissue engineering due to their favorable mechanical and structural properties. However, achieving high cell proliferation rates within these hydrogels remains a challenge. In static cultivation, the volume of the culture medium is changed once every few days. Thus, perfect perfusion is not achieved due to the relative increase in metabolic concentration and no medium flow. Therefore, in our work, we developed a culture system in which printed collagen bioinks (collagen concentration in hydrogels of 20 and 30 mg/mL with a final concentration of 10 and 15 mg/mL in bioink) where samples flow freely in the culture medium, thus enhancing the elimination of nutrients and metabolites of cells. Cell viability, morphology, and metabolic activity (MTT tests) were analyzed on collagen hydrogels with a collagen concentration of 20 and 30 mg/mL in static culture groups without medium exchange and with active medium perfusion; the influence of pure growth culture medium and smooth muscle cells differentiation medium was next investigated. Collagen isolated from porcine skins was used; every batch was titrated to optimize the pH of the resulting collagen to minimize the difference in production batches and, therefore, the results. Active medium perfusion significantly improved cell viability and activity in the high-concentrated gel, which, to date, is the most limiting factor for using these hydrogels. In addition, based on SEM images and geometry analysis, the cells remodel collagen material to their extracellular matrix.
- Publication type
- Journal Article MeSH
Transferring an existing marketed pharmaceutical product from batch to continuous manufacturing (CM) without changes in regulatory registration is a challenging task in the pharmaceutical industry. Continuous manufacturing can provide an increased production rate and better equipment utilisation while retaining key quality attributes of the final product. Continuous manufacturing necessitates the monitoring of critical quality attributes in real time by appropriate process analytical tools such as near infra-red (NIR) probes. The present work reports a successful transfer of an existing drug product from batch to continuous manufacturing process without changing the formulation. A key step was continuous powder blending, whose design and operating parameters including weir type, agitation rate, dynamic hold-up and residence time were systematically investigated with respect to process repeatability. A NIR-based multivariate data model for in-line composition monitoring has been developed and validated against an existing quality control method for measuring tablet content uniformity. A continuous manufacturing long-run with a throughput of 30 kg/h (approx. 128,000 tablets per hour), uninterrupted for 320 min, has been performed to test and validate the multivariate data model as well as the batch to continuous process transfer. The final disintegration and dissolution properties of tablets manufactured by the continuous process were found to be equivalent to those manufactured by the original batch process.
- MeSH
- Spectroscopy, Near-Infrared methods MeSH
- Chemistry, Pharmaceutical methods MeSH
- Technology, Pharmaceutical * methods MeSH
- Excipients chemistry MeSH
- Powders chemistry MeSH
- Drug Compounding methods MeSH
- Quality Control MeSH
- Solubility MeSH
- Tablets * MeSH
- Drug Liberation MeSH
- Publication type
- Journal Article MeSH
The transfer from batch-based to continuous tablet manufacturing increases the quality and efficiency of processes. Nonetheless, as in the development of a batch process, the continuous process design requires optimization studies to ensure a robust process. In this study, processing of a commercially batch-manufactured tablet product was tested with two continuous direct compression lines while keeping the original formulation composition and tablet quality requirements. Tableting runs were conducted with different values of process parameters. Changes in parameter settings were found to cause differences in tablet properties. Most of these quality properties could be controlled and maintained within the set limits effortlessly already at this stage of studies. However, the API content and content uniformity seemed to require more investigation. The observed content uniformity challenges were traced to individual tablets with a high amount of API. This was suspected to be caused by API micro-agglomerates since tablet weight variability did not explain the issue. This could be solved by adding a mill between two blenders in the process line. Overall, this case study produced promising results with both tested manufacturing lines since many tablet properties complied with the test result limits without optimization of process parameter settings.
