The objectives of the present work were to simultaneously quantify digoxin (DGX) and its impurities by a common analytical method, compare dissolution data

Angiogenesis and epithelial–mesenchymal transition (EMT) are key hallmarks that contribute to the progression of oral squamous cell carcinoma (OSCC), but whether the two programs vary simultaneously across tumors and how much of this reflects tumor composition remain unclear. We scored predefined, non-overlapping 20-gene angiogenesis and EMT signatures with a rank-based method in 342 primary oral cavity tumors from The Cancer Genome Atlas (TCGA-OSCC). The two programs were strongly correlated (Spearman ρ = 0.809, P = 2.7 × 10 ⁻⁸⁰ ), and 2,396 bridge genes were associated with both programs across the transcriptome. The bridge genes were enriched in pathways associated with focal adhesion and extracellular matrix– receptor interaction. In the cellular case, fibroblast and endothelial marker scores were prominent and correlated with the program scores. The coupling was attenuated but remained positive after joint adjustment for tumor purity and stromal and immune scores (partial ρ = 0.406) and with an epithelial-restricted EMT score (ρ = 0.710). Further correlation was performed with a partial EMT (pEMT), which shows a significant positive correlation (ρ = 0.59) and an inverse correlation with tumor purity (ρ = −0.70). 146 final gene candidates were found using multi-omic evidence and candidate-level testing on the external cohort GSE30784; after adjusting for inferred cell fractions, 101 of these candidates supported the dual program. For thorough characterization, three candidates with an emphasis on OSMR, MICAL2, and LHFPL2 were chosen. Additional CPTAC data were used to confirm protein-level support, which was strongest for MICAL2. No significant connection was seen between the Interface score and overall survival (hazard ratio per 1-SD increase, 0.92; 95% CI, 0.78–1.08). These results describe a coordinated angiogenesis–EMT transcriptional state in OSCC that is attenuated but retained after accounting for tumor composition, and nominate candidate genes for experimental study.

Background: Digoxin (DGX) is a narrow therapeutic index (NTI) and Biopharmaceutics Classification System (BCS) class IV drug whose clinical performance can be influenced by physicochemical properties, formulation composition, manufacturing processes, and stability-related solid-state transformations. Objective: The objective of the paper was to understand the effect of process and formulation variables on digoxin formulations. Methods: This study reports the effect of particle size, lactose types (LA and LM), manufacturing methods, and granulating fluid (ethanol and water–ethanol) on the critical quality attributes of DGX tablets (XRPD, DT, assay, impurity, and dissolution). Accordingly, 10 formulations were prepared using a full factorial design and monitored for 30 days at 40 °C/75% RH. Results: Assay values of the formulations did not change significantly (p > 0.05) compared to initial values after storage. No impurities or new peaks were detected in the stability samples, indicating either no drug degradation or the degradation products were below the limit of detection of the method (31.5–44.6 ng/mL). The dissolution rate and extent of the formulations changed after exposure, indicating the effect of composition and process variables. In direct compression formulations, a decrease in dissolution rate, especially at 10 and 20 min, was higher than at 60 min, which may be related to an increase in hardness and DT values. However, a decrease in dissolution of 5.6–8.7% at 60 min was observed after storage from the initial values, which may be due to an increase in crystallinity. Conclusions: Particle size, manufacturing method, and granulating fluid significantly influenced the solid-state characteristics and dissolution performance of DGX tablets. Wet granulation promoted partial amorphization and improved initial dissolution but reduced stability due to recrystallization during storage. These findings highlight the importance of formulation and process selection in ensuring the quality and stability of NTI drug products.

Three-dimensional printing (3DP) manufacturing technologies will transform pharmaceutical industry, offering the ability to produce personalized medicine a