The primary aim of the current investigation was the Analytical progression and validation of a UV-spectrophotometric analytical approach for the quantification of Nirogacestat in both bulk and pharmaceutical dosage forms, in alignment with ICH regulatory standards. A straightforward, expeditious, reliable, and economically viable UV-spectrophotometric technique was established for the quantitative determination of Nirogacestat employing acetonitrile as the solvent medium. The absorbance of the analyte solution was recorded at 269 nm relative to a suitable blank. Method validation was performed pursuant with prescribed parameters, encompassing linearity, accuracy, precision and robustness. The λmax of Nirogacestat in acetonitrile was identified at 269 nm. The analyte demonstrated compliance with Beer-Lambert’s law across the concentration interval of 2.5–15.0 μg/mL, exhibiting a correlation coefficient(R²) of 0.999. The percentage recovery ranged from 99.3% to 100.1% reflecting substantial accuracy. Precision assessments resulted %RSD values below 2.0, substantiating both repeatability and intermediate precision. Robustness evaluations involving minor alterations in wavelength exhibited negligible deviation, thereby affirming reliability. Additionally, forced degradation experiments substantiated the stability-indicating characteristics. The delineated UV-spectrophotometric technique is straightforward, analytically sensitive, and reproducible. It is eminently suitable for routine quality assessment and quantitative evaluation of Nirogacestat in bulk drug substances and tablet formulations.
Sepsis is a complex, life-threatening disease characterized by multiple organ failure due to an abnormal systemic response to infection. Its multifaceted pathophysiology involves a dynamic balance linked pro-inflammatory and anti-inflammatory mediators, coagulation activation, and altered cellular functions. Although different kinds of regulated cell death (RCD) are implicated in sepsis pathogenesis, ferroptosis has emerged as an iron-mediated cell death. Molecular drivers of ferroptosis include iron accumulation, lipid peroxidation, production of reactive oxygen species (ROS), and inhibition of Glutathione peroxidase 4 (GPX4), eventually causing cell death. Current pre-clinical studies are aimed at modulating the ferroptosis pathway, and clinical studies are exploring the therapeutic strategies across diseases. The connection between sepsis and ferroptosis is bound by cellular abnormalities participating in several RCD mechanisms, including apoptosis, pyroptosis, necroptosis, ferroptosis, and autophagy. These cellular abnormalities encompass mitochondrial shrinkage, collapse of cristae, increased membrane density, activation of unfolded protein response, hydrolytic enzyme leakage, and enhanced lysosomal degradation. Additionally, genes associated with ferroptosis, such as Mitogen-Activated Protein Kinase 14 (MAPK14), Acyl-CoA Synthetase Long-Chain Family Member (ACSL4), Ribonucleotide Reductase Regulatory Subunit M2 (RRM2), and GPX4, have altered expression during sepsis, which impacts both the susceptibility and the progression of ferroptotic cell death.
Plant sterols are naturally occurring bioactive compounds widely recognized for their cholesterol-lowering effects. This narrative review critically evaluates current evidence regarding the role of phytosterols in insulin resistance, glucose metabolism, and type 2 diabetes mellitus (T2DM). Literature was collected from PubMed, Scopus, and Google Scholar for studies Published between 2000 and 2024 using pre-defined keywords related to phytosterols, insulin resistance, and T2DM. Evidence from in-vitro and animal studies suggests that phytosterols may influence AMPK, PI3/Akt, and GLUT4 signaling pathways and may improve metabolic homeostasis. However, evidence from human clinical trials remains limited and in-consistent. Current findings strongly support the lipid-lowering benefits of phytosterols, where as their role in glycemic control requires further validation through well-designed clinical studies.
This study aims to investigate the effects of Vitamin D and EB1089 (seocalcitol), a synthetic vitamin D receptor agonist, on morphine-induced analgesia and the development of morphine tolerance in rats using thermal antinociceptive assays and plasma serotonin analysis. A total of 56 male Wistar albino rats weighing 240–260 g were used in the study. The rats were randomly assigned to 7 groups, with 8 rats in each group. Evaluation of antinociceptive activity was performed using the tail flick and hot plate methods. Serotonin levels in plasma were analyzed using the ELISA method. In the tail flick test, the morphine + vitamin D group exhibited significant analgesia compared to the control group. In the hot plate test both the morphine + vitamin D and morphine + EB1089 groups exhibited significant analgesia compared to both the control and morphine groups. Both the morphine tolerance + vitamin D and morphine tolerance + EB1089 groups showed a significant increase in pain threshold in the tail flick and hot plate tests compared to the control and morphine tolerance groups. This study demonstrates that vitamin D and EB1089 enhance the analgesic effects of morphine in rats and slow the development of morphine tolerance.
Furosemide is a loop diuretic widely prescribed for the management of edema and hypertension; however, its oral efficacy is limited by poor solubility and low permeability. According to the Biopharmaceutics Classification System, furosemide belongs to class IV, necessitating optimization at the preformulation stage to enhance its biopharmaceutical performance. This review aims to analyze various preformulation strategies that have been demonstrated to improve the solubility and oral bioavailability of furosemide through an extensive literature review of scientific publications from the past decade. The investigated approaches include particle size reduction, co-amorphous systems, micronization, solid dispersion, solvent evaporation, cyclodextrin complexation, pH adjustment, self-nanoemulsifying drug delivery systems, nanostructured lipid carriers, solid–liquid nanoparticles, nanosuspensions, and controlled precipitation methods. The review indicates that these strategies markedly enhance the dissolution rate and physical stability of furosemide through several mechanisms, such as increased surface area, amorphous phase formation, inclusion complexation, and maintenance of supersaturated states. Among the reviewed strategies, lipid-based and nanoscale delivery systems generally demonstrated greater improvements in oral bioavailability than conventional approaches, although direct comparisons should be interpreted with caution because of differences in study design, experimental conditions, and pharmacokinetic endpoints. Overall, physicochemical modification and nanotechnology-based preformulation strategies offer promising potential to overcome the solubility limitations of furosemide, thereby improving oral therapeutic efficacy and reducing interindividual pharmacokinetic variability.
