Facet Connectivity-Based Estimation Algorithm for Manufacturability of Supportless Parts Fabricated via LPBF.

Recent advances in additive manufacturing have provided more freedom in the design of metal parts; hence, the prototyping of fluid machines featuring extremely complex geometries has been investigated extensively. The fabrication of fluid machines via additive manufacturing requires significant attention to part stability; however, studies that predict regions with a high risk of collapse are few. Therefore, a novel algorithm that can detect collapse regions precisely is proposed herein. The algorithm reflects the support span over the faceted surface via propagation and invalidates overestimated collapse regions based on the overhang angle. A heat exchanger model with an extremely complex internal space is adopted to validate the algorithm. Three samples from the model are extracted and their prototypes are fabricated via laser powder bed fusion. The results yielded by the fabricated samples and algorithm with respect to the sample domain are compared. Regions of visible collapse identified on the surface of the fabricated samples are predicted precisely by the algorithm. Thus, the supporting span reflected by the algorithm provides an extremely precise prediction of collapse.

Inhaled deep eutectic solvent based-nanoemulsion of pirfenidone in idiopathic pulmonary fibrosis.

Pirfenidone (PRF), the first FDA-approved drug to treat idiopathic pulmonary fibrosis (IPF) and formulated as an oral dosage form, has many side effects. To enhance the therapeutic effect, we discovered a high-load nanoemulsion using a novel deep eutectic solvent (DES) and developed an inhalation drug with improved bioavailability. The DES of PRF and N-acetylcysteine were discovered, and their physicochemical properties were evaluated in this study. The mechanism of DES formation was confirmed by FT-IR and 1H NMR and suggested to involve hydrogen bonding. The DES nanoemulsion in which the nano-sized droplets were dispersed is optimized by mixing the DES and distilled water in a ratio. The in vivo pharmacokinetic study showed that the pulmonary route of administration is superior to that of the oral route, and the DES nanoemulsion is superior to that of the PRF solution in achieving better bioavailability and lung distribution. The therapeutic effect of PRF for IPF could be confirmed through in vivo pharmacodynamics studies, including lung function assessment, enzyme-linked immunosorbent assay, histology, and micro-computed tomography using the bleomycin-induced IPF rat model. In addition, the pulmonary route administration of PRF is advantageous in reducing the toxicity risk.

In vivo pharmacokinetic and pharmacodynamic study of co-spray-dried inhalable pirfenidone microparticles in rats.

Pirfenidone (PRF) is the first FDA-approved API in the treatment of idiopathic pulmonary fibrosis (IPF). However, PRF induces serious side effects, such as photophobia and gastrointestinal disorder. PRF inhalation can be expected with a lower effective dose and reduced side effects. In this study, PRF was prepared as inhalable co-spray-dried particles for dry powder inhalation. Mannitol, L-leucine (Leu), and NaCl were used as a stabilizer. The kinds and ratios of stabilizers affecting the physicochemical properties of particles were analyzed, including particle size and surface composition, because of the surface enrichment properties of Leu, the most effective stabilizer. The co-spray-dried PRF and Leu microparticle (SD-PL1:1) have the smallest size and highest aerosol performance. The bioavailability was confirmed by in vivo pharmacokinetics (PK) studies. In addition, in vivo pharmacodynamics (PD) experiments were conducted using a bleomycin-induced IPF rat model. In vivo PK experiments demonstrated that pulmonary administration of SD-PL1:1 was 4 times more effective than the oral route. Similar to the PK results, the therapeutic effect was improved when SD-PL1:1 was administered via the pulmonary route compared to the oral route.

Co-Spray Dried Nafamostat Mesylate with Lecithin and Mannitol as Respirable Microparticles for Targeted Pulmonary Delivery: Pharmacokinetics and Lung Distribution in Rats.

Coronavirus disease 2019 (COVID-19), caused by a new strain of coronavirus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is spreading rapidly worldwide. Nafamostat mesylate (NFM) suppresses transmembrane serine protease 2 and SARS-CoV-2 S protein-mediated fusion. In this study, pharmacokinetics and lung distribution of NFM, administered via intravenous and intratracheal routes, were determined using high performance liquid chromatography analysis of blood plasma, lung lumen using bronchoalveolar lavage fluid, and lung tissue. Intratracheal administration had higher drug delivery and longer residual time in the lung lumen and tissue, which are the main sites of action, than intravenous administration. We confirmed the effect of lecithin as a stabilizer through an ex vivo stability test. Lecithin acts as an inhibitor of carboxylesterase and delays NFM decomposition. We prepared inhalable microparticles with NFM, lecithin, and mannitol via the co-spray method. The formulation prepared using an NFM:lecithin:mannitol ratio of 1:1:100 had a small particle size and excellent aerodynamic performance. Spray dried microparticles containing NFM, lecithin, and mannitol (1:1:100) had the longest residual time in the lung tissue. In conclusion, NFM-inhalable microparticles were prepared and confirmed to be delivered into the respiratory tract, such as lung lumen and lung tissue, through in vitro and in vivo evaluations.

A Study on the Mechanical Properties of an Automobile Part Additively Printed through Periodic Layer Rotation Strategies.

In metal product manufacturing, additive manufacturing (AM) is a method that has the advantage of fabricating complex shapes and customized production, unlike existing machining methods. However, owing to the characteristics of the AM process, anisotropy of macrostructure occurs because of various causes such as the scan direction, melting, fusion, and cooling of the powdered material. The macrostructure anisotropy is realized from the scan direction, and when a single layer is stacked in one direction, it is expressed as orthogonal anisotropy. Here, the classical lamination theory is applied to simply calculate the individual orthotropic layers by superimposing them. Through this, the authors analyzed whether the mechanical properties of the product are isotropically expressed with a periodic layer rotation strategy. To determine if the mechanical properties can be reasonably considered to be isotropic, a shock absorber mount for a vehicle was manufactured by AM. The tensile and vibration test performed on the product was compared with the finite element analysis and experimental results. As a result of the comparison, it was confirmed that the macroscopically of the product was considered isotropic as the load-displacement diagram and the fracture location coincided, as well as the natural frequency and mode shape.

Phenotypes of Severe Cutaneous Adverse Reactions Caused by Nonsteroidal Anti-inflammatory Drugs.

PURPOSE: Nonsteroidal anti-inflammatory drugs (NSAIDs) are common cause of severe cutaneous adverse reactions (SCARs). The present study aimed to investigate the characteristics of SCARs induced by NSAIDs in the Korean SCAR registry. METHODS: A retrospective survey of NSAID-induced SCARs recorded between 2010 and 2015 at 27 university hospitals in Korea was conducted. Clinical phenotypes of SCARs were classified into Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), SJS-TEN overlap syndrome and drug reaction with eosinophilia and systemic symptoms (DRESS). Causative NSAIDs were classified into 7 groups according to their chemical properties: acetaminophen, and propionic, acetic, salicylic, fenamic and enolic acids. RESULTS: A total of 170 SCARs, consisting of 85 SJS, 32 TEN, 17 SJS-TEN overlap syndrome and 36 DRESS reactions, were induced by NSAIDs: propionic acids (n=68), acetaminophen (n=38), acetic acids (n=23), salicylic acids (n=16), coxibs (n=8), fenamic acids (n=7), enolic acids (n=5) and unclassified (n=5). Acetic acids (22%) and coxibs (14%) accounted for higher portions of DRESS than other SCARs. The phenotypes of SCARs induced by both propionic and salicylic acids were similar (SJS, TEN and DRESS, in order). Acetaminophen was primarily associated with SJS (27%) and was less involved in TEN (10%). DRESS occurred more readily among subjects experiencing coxib-induced SCARs than other NSAID-induced SCARs (62.5% vs. 19.7%, P = 0.013). The mean time to symptom onset was longer in DRESS than in SJS or TEN (19.1 ± 4.1 vs. 6.8 ±1.5 vs. 12.1 ± 3.8 days). SCARs caused by propionic salicylic acids showed longer latency, whereas acetaminophen- and acetic acid-induced SCARs appeared within shorter intervals. CONCLUSIONS: The present study indicates that the phenotypes of SCARs may differ according to the chemical classifications of NSAIDs. To establish the mechanisms and incidences of NSAID-induced SCARs, further prospective studies are needed.

A retrospective analysis of 19,157 burns patients: 18-year experience from Hallym Burn Center in Seoul, Korea.

This is a retrospective, epidemiological study of 19,157 acute burn patients admitted to the Hallym Burn Centre, Hangang Sacred Heart Hospital, Seoul, Korea, during the period 1986-2003. The study was conducted to identify characteristics of burn patients that could lead to development of preventive programs to reduce both the frequency and mortality of burn injury. The majority of patients admitted had relatively minor burns, which were treated conservatively. Males predominated in all age groups with a summer peak seasonal variation. Typical burn in the children <5 years of age was a scald injury, occurring at home, affecting upper limbs and resulting in a relatively short hospital stay. Electrical burns due to steel chopsticks and steam burns due to electric rice cookers were also found in this age group. Adult burns, affecting upper and lower limbs, were caused by flames, hot liquids or electricity. Burns were sustained at the workplace and outdoors. Flame accidents in males were the leading cause of death with overall mortality of 8.2%. 13.9% of admissions needed intensive care and average length of hospital stay was 32.6 days. The annual number of patients undergoing burn related surgery has continuously increased reflecting a more aggressive surgical management. Our ongoing efforts are to promote prevention program and look for changes in the incidence of burn injury based on these epidemiologic features. Further study for implications of changes in management protocols and policies on treatment outcomes would improve the provision of appropriate care for the patients.