Search Results (61)

Background: Fexofenadine hydrochloride (FEX) is widely used to treat allergic rhinitis. However, poor solubility, high cohesiveness, and risk of polymorphic transformation present significant formulation challenges. Conventional FEX tablet formulations are large and may pose swallowing difficulties for patients with dysphagia. Therefore, a miniaturized FEX tablet that maintained bioequivalence with the marketed product was developed. Methods: An organic solvent-based binder and porous carrier enhanced solubility, flowability, and process efficiency. The formulation was optimized using a design of experiments approach to assess the effects of tablet size and porous carrier incorporation on dissolution and residual solvent content. Scale-up feasibility was evaluated using Froude number-based process optimization, and stability studies were conducted under accelerated conditions (40 °C and 75% relative humidity) to ensure long-term formulation robustness. Results: The miniaturized tablet exhibited dissolution at pH 4.0 and pH 6.8 equivalent to that of the reference product, whereas a faster dissolution rate was observed at pH 1.2. No significant changes were observed in the dissolution rate, crystalline structure, or impurity levels over six months. An in vivo bioequivalence study demonstrated that the test formulation met the bioequivalence criteria, with 90% confidence intervals for the area under the curve and the C_max falling within the regulatory acceptance range. Conclusions: A miniaturized and commercially viable fexofenadine hydrochloride tablet was developed (44% weight reduction and 50% volume reduction compared to the marketed product). The organic solvent-based binder and porous carrier system improved manufacturing efficiency, stability, and solubility, thereby ensuring compliance with regulatory standards. These findings provide valuable insights into size reduction, solubility enhancement, and large-scale production strategies for the development of future pharmaceutical formulations. Full article

Background: This study aimed to optimize the coating process of Omega-3 fatty acid (OM3-FA) mini soft capsules containing the active pharmaceutical ingredients (APIs) pitavastatin and ezetimibe using near-infrared (NIR) spectroscopy for in-process monitoring. Cardiovascular disease treatments benefit from combining OM3-FA with lipid-lowering agents, but formulating such combinations in mini soft capsules presents challenges in maintaining stability and mechanical integrity. Methods: The coating process was developed using a pan coater and real-time NIR monitoring to ensure uniformity and quality. NIR spectroscopy enabled precise control of coating thickness, ensuring consistent drug distribution across the capsule surface. Results: The optimized process minimized OM3-FA oxidation and preserved the mechanical integrity of the capsules, as confirmed by texture analysis and in-vitro dissolution testing. This integration of NIR spectroscopy as a process analytical technology (PAT) significantly improved coating quality control, resulting in a stable and effective combination therapy for pitavastatin and ezetimibe in a mini soft capsule form. Conclusion: This approach offers an efficient solution for enhancing patient adherence in cardiovascular disease management. The application of NIR spectroscopy for real-time monitoring highlights its broader significance in pharmaceutical manufacturing, where it can serve as a versatile tool for ensuring product quality and optimizing production efficiency in diverse formulation processes. By incorporating NIR-based PAT, manufacturers can not only achieve product-specific improvements but also establish a foundation for continuous manufacturing and automated quality assurance systems, ultimately contributing to a more streamlined and robust production environment. Full article

An increase in the number of small electronics is anticipated, requiring the preparation of an adequate powering method. A triboelectric nanogenerator, capable of scavenging ambient mechanical energy, is proposed as an efficient means to reduce power consumption for self-sustainable sensors, although its electrical output needs enhancement to broaden its technological applicability. In this work, a magnetic composite comprising iron oxide and polyaniline was synthesized to augment triboelectricity through the modulation of magnetic field intensity using physical chemistry. The crystallinity of the composite, chemical bonding, and structure of the surface are analyzed. The surface potential of the composite, embedded into polydimethylsiloxane, is quantitatively evaluated by using Kelvin probe force microscopy. By amalgamating magnetic flux density and triboelectric outputs, the optimization of the triboelectric layer is achieved, yielding output values of 93.86 V, 6.9 µA, and 127.5 µW. Following a reduction in surface adhesion after the powder coating process, a wind-based triboelectric nanogenerator is fabricated. Its excellent sensitivity to wind and exceptional long-term endurance are assessed, confirming its suitability as a sensor. The practicality of employing this device in intrusion detection, leveraging a wireless door-opening sensor, is demonstrated using synthesized composite materials. Full article

Dry-powder inhalers (DPIs) are valued for their stability but formulating them is challenging due to powder aggregation and limited flowability, which affects drug delivery and uniformity. In this study, the incorporation of L-leucine (LEU) into hot-melt extrusion (HME) was proposed to enhance dispersibility while simultaneously maintaining the high aerodynamic performance of inhalable microparticles. This study explored using LEU in HME to improve dispersibility and maintain the high aerodynamic performance of inhalable microparticles. Formulations with crystalline itraconazole (ITZ) and LEU were made via co-jet milling and HME followed by jet milling. The LEU ratio varied, comparing solubility, homogenization, and aerodynamic performance enhancements. In HME, ITZ solubility increased, and crystallinity decreased. Higher LEU ratios in HME formulations reduced the contact angle, enhancing mass median aerodynamic diameter (MMAD) size and aerodynamic performance synergistically. Achieving a maximum extra fine particle fraction of 33.68 ± 1.31% enabled stable deep lung delivery. This study shows that HME combined with LEU effectively produces inhalable particles, which is promising for improved drug dispersion and delivery. Full article

The aim of this study was to fabricate mini-tablets of polyhedrons containing theophylline using a fused deposition modeling (FDM) 3D printer, and to evaluate the correlation between release kinetics models and their geometric shapes. The filaments containing theophylline, hydroxypropyl cellulose (HPC), and EUDRAGIT RS PO (EU) could be obtained with a consistent thickness through pre-drying before hot melt extrusion (HME). Mini-tablets of polyhedrons ranging from tetrahedron to icosahedron were 3D-printed using the same formulation of the filament, ensuring equal volumes. The release kinetics models derived from dissolution tests of the polyhedrons, along with calculations for various physical parameters (edge, SA: surface area, SA/W: surface area/weight, SA/V: surface area/volume), revealed that the correlation between the Higuchi model and the SA/V was the highest (R² = 0.995). It was confirmed that using 3D- printing for the development of personalized or pediatric drug products allows for the adjustment of drug dosage by modifying the size or shape of the drug while maintaining or controlling the same release profile. Full article

Breeding for stress-tolerant hybrids begins with screening germplasm for tolerant genotypes. We employed a non-destructive and objective method to evaluate the low-temperature response of sweet corns at the seedling stage, using a digital image analysis. It was estimated using summed leaf area, a new parameter defined as the sum of the leaf area measured from images taken at different angles. The summed leaf area, SPAD, shoot and root fresh weight, and total root length were significantly different among hybrids. The group mean of sugary endosperm type was significantly higher than that of shrunken type for all traits but SPAD. For the summed leaf area, the top three ranked hybrids were from the sugary type, but the area for the following three hybrids from the shrunken type did not differ from that for the first three hybrids. The summed leaf area was correlated with SPAD (r = 0.49 **), shoot (r = 0.99 **) and root (r = 0.93 **) fresh weight, and total root length (r = 0.76 **). Phytoglycogen in seeds only had a significant correlation (r = 0.46 **) with the area. The summed leaf area of only one hybrid differed between normal- and low-temperature conditions. The low-temperature response based on the summed leaf area was reflected in the field condition, with a few exceptions. The results suggest that the summed leaf area via digital image analysis can be used to evaluate low-temperature response in sweet corns. Full article

Due to the short storage period, large quantities of platelet concentrate (PC) are expiring. The expired PC cannot be injected into a blood vessel, but the activity of bioactive molecules, especially growth factors, is still preserved. In this paper, we organized a process to obtain a growth factor-rich bioproduct for use as a supplement in human cell culture by optimizing freezing, thawing, and sterilization conditions. Each unit of PC displayed visual differences, diverse biochemical values, and growth factor concentrations. To minimize lot-to-lot variation, we pooled a minimum of 10 PC units. The concentrations of growth factors were maximized through five freeze–thaw cycles for 12 h at −80 °C for freezing and for 5 min at 36 °C for thawing. We used a cell strainer with 40 µm pores, followed by a 0.45 μm filter and a 0.22 μm filter sequentially to sterilize the bioproduct with minimizing loss. The obtained growth factors remained stable for 4–6 h at room temperature (23 °C), 24 h at 4 °C, and 12 months at −80 °C. Cellular responses to the growth factor-rich bioproduct were tested with primary human renal proximal tubule epithelial cells. The cells exhibited a significantly increased growth rate, compared to the fetal bovine serum (FBS)-treated control group. The cells maintained their characteristic cuboidal shape, and stem cells and renal progenitor cells also preserved their genetic characteristics during culture. Therefore, the growth factor-rich bioproduct isolated from expired PC through our process can be used as a medium supplement to replace FBS in human cell culture for clinical application. Full article

In the field of computer vision, convolutional neural network (CNN)-based models have demonstrated high accuracy and good generalization performance. However, in semantic segmentation, CNN-based models have a problem—the spatial and global context information is lost owing to a decrease in resolution during feature extraction. High-resolution networks (HRNets) can resolve this problem by keeping high-resolution processing layers parallel. However, information loss still occurs. Therefore, in this study, we propose an HRNet combined with an attention module to address the issue of information loss. The attention module is strategically placed immediately after each convolution to alleviate information loss by emphasizing the information retained at each stage. To achieve this, we employed a squeeze-and-excitation (SE) block as the attention module, which can seamlessly integrate into any model and enhance the performance without imposing significant parameter increases. It emphasizes the spatial and global context information by compressing and recalibrating features through global average pooling (GAP). A performance comparison between the existing HRNet model and the proposed model using various datasets show that the mean class-wise intersection over union (mIoU) and mean pixel accuracy (MeanACC) improved with the proposed model, however, there was a small increase in the number of parameters. With cityscapes dataset, MeanACC decreased by 0.1% with the proposed model compared to the baseline model, but mIoU increased by 0.5%. With the LIP dataset, the MeanACC and mIoU increased by 0.3% and 0.4%, respectively. The mIoU also decreased by 0.1% with the PASCAL Context dataset, whereas the MeanACC increased by 0.7%. Overall, the proposed model showed improved performance compared to the existing model. Full article

The causal effects of chondroitin, glucosamine, and vitamin/mineral supplement intake on kidney function remain unknown, despite being commonly used. We conducted a two-sample summary-level Mendelian randomization (MR) analysis to test for causal associations between regular dietary supplement intake and kidney function. Genetic instruments for chondroitin, glucosamine, and vitamin/mineral supplement intake were obtained from a genome-wide association study of European ancestry. Summary statistics for the log-transformed estimated glomerular filtration rate (log-eGFR) were provided by the CKDGen consortium. The multiplicative random-effects inverse-variance weighted method showed that genetically predicted chondroitin and glucosamine intake was causally associated with a lower eGFR (chondroitin, eGFR change beta = −0.113%, standard error (SE) = 0.03%, p-value = 2 × 10⁻⁴; glucosamine, eGFR change beta = −0.240%, SE = 0.035%, p-value = 6 × 10⁻¹²). However, a genetically predicted vitamin/mineral supplement intake was associated with a higher eGFR (eGFR change beta = 1.426%, SE = 0.136%, p-value = 1 × 10⁻²⁵). Validation analyses and pleiotropy-robust MR results for chondroitin and vitamin/mineral supplement intake supported the main results. Our MR study suggests a potential causal effect of chondroitin and glucosamine intake on kidney function. Therefore, clinicians should carefully monitor their long-term effects. Full article

The conventional dosage form of Ethyol^® (amifostine), a sterile lyophilized powder, involves reconstituting it with 9.7 mL of sterile 0.9% sodium chloride in accordance with the United States Pharmacopeia specifications for intravenous infusion. The purpose of this study was to develop inhalable microparticles of amifostine (AMF) and compare the physicochemical properties and inhalation efficiency of AMF microparticles prepared by different methods (jet milling and wet ball milling) and different solvents (methanol, ethanol, chloroform, and toluene). Inhalable microparticles of AMF dry powder were prepared using a wet ball-milling process with polar and non-polar solvents to improve their efficacy when delivered through the pulmonary route. The wet ball-milling process was performed as follows: AMF (10 g), zirconia balls (50 g), and solvent (20 mL) were mixed and placed in a cylindrical stainless-steel jar. Wet ball milling was performed at 400 rpm for 15 min. The physicochemical properties and aerodynamic characteristics of the prepared samples were evaluated. The physicochemical properties of wet-ball-milled microparticles (WBM-M and WBM-E) using polar solvents were confirmed. Aerodynamic characterization was not used to measure the % fine particle fraction (% FPF) value in the raw AMF. The % FPF value of JM was 26.9 ± 5.8%. The % FPF values of the wet-ball-milled microparticles WBM-M and WBM-E prepared using polar solvents were 34.5 ± 0.2% and 27.9 ± 0.7%, respectively; while the % FPF values of the wet-ball-milled microparticles WBM-C and WBM-T prepared using non-polar solvents were 45.5 ± 0.6% and 44.7 ± 0.3%, respectively. Using a non-polar solvent in the wet ball-milling process resulted in a more homogeneous and stable crystal form of the fine AMF powder than using a polar solvent. Full article

Itching is an unpleasant sensation that provokes the desire to scratch. In general, itching is caused by dermatologic diseases, but it can also be caused by systemic diseases. Since itching hampers patients’ quality of life, it is important to understand the appropriate treatment and pathophysiology of pruritus caused by systemic diseases to improve the quality of life. Mechanisms are being studied through animal or human studies, and various treatments are being tested through clinical trials. We report current trends of two major systemic diseases: chronic kidney disease and cholestatic liver disease. This review summarizes the causes and pathophysiology of systemic diseases with pruritus and appropriate treatments. This article will contribute to patients’ quality of life. Further research will help understand the mechanisms and develop new strategies in the future. Full article

Itching is a sensory phenomenon characterized by an unpleasant sensation that makes you want to scratch the skin, and chronic itching diminishes the quality of life. In recent studies, multiple transient receptor potential (TRP) channels present in keratinocytes or nerve endings have been shown to engage in the propagation of itch signals in chronic dermatological or pruritic conditions, such as atopic dermatitis (AD) and psoriasis (PS). TRPV3, a member of the TRP family, is highly expressed in the epidermal keratinocytes. Normal TRPV3 signaling is essential for maintaining epidermal barrier homeostasis. In recent decades, many studies have suggested that TRPV3 contributes to detecting pruritus signals. Gain-of-function mutations in TRPV3 in mice and humans are characterized by severe itching, hyperkeratosis, and elevated total IgE levels. These studies suggest that TRPV3 is an important channel for skin itching. Preclinical studies have provided evidence to support the development of TRPV3 antagonists for treating inflammatory skin conditions, itchiness, and pain. This review explores the role of TRPV3 in chronic pruritus, collating clinical and experimental evidence. We also discuss underlying cellular and molecular mechanisms and explore the potential of TRPV3 antagonists as therapeutic agents. Full article

G protein–coupled receptors (GPCRs) are a diverse family of cell surface receptors implicated in various physiological functions, making them common targets for approved drugs. Many GPCRs are abnormally activated in cancers and have emerged as therapeutic targets for cancer. Neuropeptide FF receptor 2 (NPFFR2) is a GPCR that helps regulate pain and modulates the opioid system; however, its function remains unknown in cancers. Here, we found that NPFFR2 is significantly up-regulated in liver cancer and its expression is related to poor prognosis. Silencing of NPFFR2 reduced the malignancy of liver cancer cells by decreasing cell survival, invasion, and migration, while its overexpression increased invasion, migration, and anchorage-independent cell growth. Moreover, we found that the malignant function of NPFFR2 depends on RhoA and YAP signaling. Inhibition of Rho kinase activity completely restored the phenotypes induced by NPFFR2, and RhoA/F-Actin/YAP signaling was controlled by NPFFR2. These findings demonstrate that NPFFR2 may be a potential target for the treatment of hepatocellular carcinoma. Full article

Glycosylated hemoglobin (HbA1c) is an established marker associated with cardiovascular risk, even if it is below the diagnostic threshold for diabetes mellitus (DM). However, whether or not prediabetic and controlled diabetic levels of HbA1c are associated with increased major adverse cardiovascular events (MACE) after percutaneous coronary intervention (PCI) remains unclear. This observational study included a total of 9128 patients who underwent PCI in the COACT registry from eight centers in Korea. A total of 2517 non-DM patients were divided into three groups (Groups I, II, III) according to their HbA1c levels and compared with 965 controlled DM patients (HbA1c < 7.0%, Group IV). During 22 months of median follow-up, there was no significant differences in MACE (p = 0.294) and cardiac death (p = 0.105) among the four groups. In addition, there were also no significant differences in MACE (p = 0.058) between Group III and Group IV. Although patients were diagnosed as DM, they had a similar prognosis in the same range of newly diagnosed DM patients in HbA1c, if they were treated well. The results of this study suggest that intensive treatment is required to reach the Hba1c target in diabetic patients with PCI in order to have a similar prognosis to patients not previously diagnosed with diabetes. Full article

No definitive criteria regarding the performance of preoperative chest computed tomography (CT) in patients with cT1a renal cell carcinoma (RCC) exists. We aimed to establish an objective standard for the optimal timing of preoperative chest CT in patients with RCC. Data from 890 patients who underwent surgical treatment for RCC between January 2011 and December 2020 were retrospectively collected. The primary endpoint was detection of lung metastasis on chest CT before nephrectomy. A multivariable logistic regression model predicting positive chest CT scans was used. Predictors included preoperative cTN stage, presence of systemic symptoms, Charlson comorbidity index (CCI), platelet count/hemoglobin ratio, albumin/globulin ratio (AGR), and De Ritis ratio. The overall rate of positive chest CT scans before nephrectomy was 3.03% (27/890). Only one patient had lung metastasis before surgery for cT1a. cT stage (≥cT1b), CCI ≥4, and low AGR were associated with a higher risk of positive chest CT scans. The best cutoff value for AGR was 1.39. After 890-sample bootstrap validation, the concordance index was 0.80. The net benefit of the proposed strategy was superior to that of the select-all and select-none strategies according to decision curve analysis. Therefore, when chest CT scans were performed with a risk of a positive result ≥10%, 532 (59.8%) negative chest CT scans could be prevented. Only 24 (2.7%) potentially positive chest CT scans were misdiagnosed. Therefore, we recommend chest CT in patients with ≥cT1b disease, CCI ≥4, and low AGR. Full article