Search Results (1,252)

Background: Enjoyment in sport has emerged as a key psychological factor influencing exercise adherence and cognitive and emotional development. This exploratory study examined pre–post changes in selected cognitive and motor variables over a 15-week observation period and whether average enjoyment during soccer training was associated with cognitive and motor performance indices. Fifty-six players (M = 52; F = 4; age: 9.98 ± 0.70) were observed across 30 soccer training sessions over 15 weeks. Methods: Enjoyment was rated after each session using an emoji-based visual analogue scale, and cognitive performance was assessed before and after the observation period with tablet-based tasks. Results: Pre–post analyses showed significant changes in the Motor Efficiency Test (t55 = 3.15; p = 0.003; Δ = −19.4%; Cohen’s d = 0.42) and FlankTime (W = 1345; p < 0.001; Δ = −8.1%; rank-biserial correlation = 0.68). FlankAcc showed only a nominal, uncorrected distributional change (W = 323; p = 0.015; Δ = 0.0%). Enjoyment was not significantly associated with any of the cognitive or motor performance indices. However, enjoyment scores were clustered toward the upper end of the scale, indicating restricted variability that may have limited the ability to detect associations. Conclusions: These preliminary findings indicate changes in selected cognitive and motor indices over the 15-week observation period, without evidence of direct associations between perceived enjoyment and the cognitive or motor performance indices examined. Full article

Rapid identification of free thiols is essential in pharmaceutical quality control and food safety. Herein, we demonstrate the sensing concept of “two signals from one event” by exploiting the intrinsic dual functionality of selenium (Se) nanomaterials to construct a signal-on, dual-mode sensing platform for free thiols. The single event is thiol-triggered seeded growth: free thiols interact with L-cysteine-modified Se seeds, driving seed fusion and crystallization into chiral trigonal Se structures. This same event yields two readouts simultaneously: a colorimetric response arising from particle size enlargement (UV-Vis red-shift) and a turn-on circular dichroism (CD) signal from long-range chiral ordering. The method achieves a detection threshold of 10 μmol/L for various free thiols and can be completed within 60 min from seed preparation to signal readout without complex instrumentation. It serves as a general indicator of total free thiols rather than distinguishing individual thiol species. Above the threshold, concentration-dependent color deepening and spectral redshifts provide semi-quantitative estimation of the concentration range. Its practicality was validated by detecting D-penicillamine in commercial tablets. This strategy offers an approach for on-site free thiol screening and highlights the potential of chiral inorganic nanomaterials in multi-mode sensing via chiral transfer and amplification. Full article

Background/Objectives: Psoriasis is a chronic inflammatory skin disease driven by Th17/Treg imbalance. Colquhounia Root Tablet (CRT), derived from Tripterygium hypoglaucum, has shown clinical potential for psoriasis, but its mechanisms remain unclear. This study aimed to evaluate the anti-psoriatic effects of CRT and elucidate its underlying mechanisms. Methods: Anti-psoriatic activity was evaluated in an IMQ-induced psoriasis-like mouse model. Mice received oral CRT at 0.085, 0.17, or 0.35 g/kg daily from days 2 to 8. Immune-cell populations were analyzed by flow cytometry. Bone marrow-derived dendritic cells (BMDCs) were used for in vitro studies. Network pharmacology, transcriptomics, molecular docking, and experimental validation were integrated to explore the mechanisms. Results: CRT dose-dependently ameliorated psoriasiform dermatitis and reduced Th17/Treg ratio while inhibiting CD11c⁺MHC II⁺ DC activation in vivo. In vitro, CRT suppressed R848-induced BMDC maturation and inhibited p65/IκBα phosphorylation. Transcriptomic analysis revealed modulation of TNF, NF-κB, IL-17, and JAK-STAT pathways. Molecular docking predicted the strong binding of multiple CRT compounds to RELA. Conclusions: CRT exerts anti-psoriatic effects in a murine model with concurrent modulation of NF-κB-related DC maturation and Th17/Treg correction, suggesting a potential immunomodulatory mechanism requiring further causal validation. Full article

Background/Objectives: Functional constipation is common in older adults and impairs quality of life. Evidence for multi-strain orally disintegrating (OD) probiotic formulations in this population remains limited. Methods: In this single-center, open-label, single-arm pre–post study, adults aged 65–90 years meeting the Rome IV criteria for functional constipation were administered an OD tablet containing Bacillus subtilis TO-A, Enterococcus faecium T-110, and Clostridium butyricum TO-A for 8 weeks. The primary endpoint was change in the defecation score based on a modified Bristol Stool Form Scale. Secondary endpoints included stool frequency, straining, JPAC-QOL, the modified Constipation Scoring System, Izumo Scale, Dietary Variety Score (DVS), selected metabolic/nutritional variables, and exploratory gut microbiota analyses. Results: Fifty participants provided consent, and 49 were included in the full analysis set; 45 participants completed the 8-week intervention and were included in the paired primary endpoint analysis. The defecation score showed a nominally significant change toward normalization of stool form at week 8 (IQR: −1.0, 7.0; 95%CI: −9.6, −4.2). Stool frequency did not change significantly, whereas constipation-related quality of life and symptom burden significantly changed. DVS increased modestly, and HbA1c decreased slightly; however, these secondary findings should be interpreted as exploratory because no adjustment for multiplicity was performed. Four patients withdrew from this study: one was due to death, but a causal relationship with the study drug was not confirmed. Two gastrointestinal adverse events could have been related to the study product. Exploratory subgroup analyses suggested a larger change in participants not receiving acid-suppressive therapy. Conclusions: The three-strain OD probiotic tablet was associated with changes in stool form and constipation-related symptom burden in older adults with functional constipation. Because this was a single-arm, open-label study without multiplicity adjustment for secondary endpoints, the findings should be regarded as exploratory and hypothesis-generating. Given the absence of a control group, causal efficacy cannot be inferred, and placebo effects, natural symptom fluctuation, or other time-varying confounders cannot be excluded; therefore, the most robust conclusion is that the preparation appeared safe and well tolerated for over 8 weeks in this population. Full article

Tablet sticking remains a persistent manufacturing challenge in solid oral dosage forms, particularly for high-drug-load formulations, where increased API surface exposure promotes adhesion to tablet punches. Generally, glidants are used to improve powder flow; their role in tablet sticking remains insufficiently understood. This study presents a material-sparing and predictive framework that utilizes powder rheology to calculate cohesion and adhesion forces. The predicted sticking rank order was experimentally validated through tablet compression studies. We systematically investigated the effects of glidant type (Aerosil^® 200, Syloid^® 244, and talc), concentration (0–2.0% w/w), and five distinct punch surfaces (Chromium Nitride (CrN), Hard Chromium (HCr), Zirconium Nitride (ZrN), S7 tool steel (S7), and Böhler M340 premium stainless steel (M340) on high-drug-load acetaminophen as a model drug. Formulations were characterized using shear-cell testing, wall-friction testing, flow-function analysis, and permeability measurements, followed by validation through tablet compression studies. Among the glidants investigated, Aerosil^® 200 showed the greatest effectiveness by reducing sticking propensity, improving flowability, crushing strength, minimizing air entrapment, and tablet weight variability. Syloid^® 244 exhibited moderate effectiveness, while talc showed the least benefit. Punch surfaces further influenced sticking behavior, with M340 exhibiting the lowest sticking tendency and ZrN the highest. The combination of 2.0% w/w Aerosil^® 200 and the M340 punch surface has the lowest Sticking Index (0.25) and the longest time to stick on the punch (659 ± 9 s). Statistical analysis confirmed that increasing the glidant from 1.0% to 2.0% did not significantly affect tablet sticking, suggesting a threshold effect. Overall, this material-sparing framework provides a mechanistic link between powder rheology and compaction outcomes, enabling early prediction of tablet sticking and rational selection of glidants and punch materials during formulation development. Full article

Background/Objectives: The administration of medicines via enteral feeding tubes presents unique challenges, including dose loss, tube blockage, and user-dependent variability. Although Quality by Design (QbD) frameworks provide a structured approach to product quality, administration-related quality attributes are rarely assessed in a systematic manner during pharmaceutical development. A conceptual framework, termed the Quality Target Administration Profile (QTAP), was developed to extend QbD principles to the administration stage. Methods: The framework comprises three phases: administration context characterization, administration attribute identification, and risk-based determination of Critical Administration Attributes (CAAs). QTAP was applied to three representative EFT administration scenarios: a ready-to-use oral suspension, a crushed tablet, and an oral solution. Results: Application of the framework identified 18–32 administration attributes across the three representative scenarios and prioritized 5–6 CAAs per scenario according to clinical impact, variability risk, and human-factor considerations. Administration quality requirements varied across scenarios, reflecting differences in administration context, including dosage form, patient population, clinical setting, and user characteristics. QTAP provides a structured approach for identifying and prioritizing administration-related quality considerations within pharmaceutical development. Conclusions: As a conceptual framework, QTAP is intended to complement rather than replace existing QbD approaches. Future prospective validation, including human-factor studies and real-world evaluations, is needed to establish its practical utility and predictive value. Full article

The translation of underutilized botanical resources into advanced therapeutic dosage forms represents a critical frontier in pharmaceutical sciences. This study systematically characterizes the phytochemical and biological profiles of three Acanthus species (Acanthus ebracteatus, Acanthus ilicifolius, and Acanthus montanus) to develop a functional, rapid-release effervescent mouthwash tablet for oral mucosal repair. Phytochemical screening demonstrated that ethanolic extraction selectively concentrated bioactive phenolics and saponins compared to conventional aqueous methods. The ethanolic A. montanus extract emerged as the premier candidate, exhibiting the highest total phenolic content, excellent biocompatibility with human gingival fibroblasts, and significant promotion of in vitro cellular migration. Furthermore, it demonstrated robust, broad-spectrum antimicrobial efficacy against key cariogenic (Streptococcus mutans) and opportunistic (Candida albicans) oral pathogens. To transition this botanical discovery into a viable delivery system, the optimized extract was integrated into an effervescent base via wet granulation utilizing absolute ethanol, followed by blending with extragranular excipients and single-stroke compression. The resulting optimized matrix, incorporating 10% sodium starch glycolate, achieved an ideal mechanical-kinetic balance, yielding exceptional structural toughness (0.23% friability) and rapid disintegration (2.02 min). Advanced 3D synchrotron X-ray tomographic microscopy revealed that this specific super-disintegrant ratio generates a highly interconnected, porous internal architecture driving accelerated capillary-mediated breakdown. Ultimately, this study successfully translates a botanical extract into a mechanistically optimized, functionally validated dosage form for targeted oral therapies. Full article

Background/Objectives: Digital self-triage tools may support patient-flow management in crowded emergency departments (EDs), but their agreement with established professional triage systems requires prospective validation. We evaluated the agreement and classification performance of a locally developed mobile self-triage application, structured according to Manchester Triage System (MTS)-related urgency logic, compared with professional MTS assessment in adult ED patients. Methods: This prospective, observational, single-center agreement study included 2274 consecutive, hemodynamically stable adult walk-in patients who used a tablet-based application covering 11 predefined presenting complaints and subsequently underwent a single, blinded professional MTS assessment, which served as the prespecified comparator. Of 3244 initial registrations, 970 (29.9%) were excluded because their complaints were not covered by the predefined pathways. MTS Categories 2–3 were classified as urgent. Results: Exact agreement occurred in 968 patients (42.6%); 1161 patients (51.1%) were overtriaged and 145 (6.3%) were undertriaged. The application showed 93.9% sensitivity, 28.7% specificity, 61.1% positive predictive value, and 79.8% negative predictive value for identifying professional MTS-defined urgent cases. Agreement was slight by unweighted kappa (κ = 0.198), fair by quadratically weighted kappa (κw = 0.278), and the prevalence- and bias-adjusted kappa for binary urgent/non-urgent classification was 0.28. Overtriage exceeded 70% for headache and low back pain, and these complaints were the strongest independent predictors of overtriage; higher self-reported pain intensity was strongly associated with overtriage. Conclusions: The application demonstrated a conservative classification profile with high sensitivity and a low undertriage rate but frequent overtriage that would inflate the apparent urgent caseload if the tool were used unsupervised; it should be considered an adjunct to, rather than a replacement for, professional triage. Findings apply to stable adult walk-in patients whose complaints matched the predefined categories and may not generalize to the broader ED population. Full article

Background/Objectives: Bisoprolol fumarate (BF) is a cardioselective beta-blocker used to treat pediatric heart failure and certain tachyarrhythmias. Currently, it is administered mainly as extemporaneously prepared suspensions from crushed tablets, which may cause issues with dose accuracy, stability, and palatability. Orodispersible minitablets (MODTs) may facilitate administration and individualized dosing, while prolonged release could potentially reduce peak-to-trough fluctuations and, thus, minimize adverse effects such as hypotension or bradycardia. This proof-of-concept study aimed to develop spray-dried prolonged-release microparticles containing BF, incorporate them into MODTs, and evaluate the effect of compression on drug release. Methods: Microparticles were prepared by spray drying ethanolic solutions of BF and ethylcellulose at 40 °C, 50 °C, and 60 °C. Their characterization included scanning electron microscopy, X-ray diffraction, differential scanning calorimetry, thermogravimetric analysis and dissolution studies. Selected microparticles were compressed into 3 mm MODTs, which were evaluated for mechanical properties, disintegration, and BF release. Results: Formulations containing 10% BF and 90% ethylcellulose released from 52.6% to 73% of BF after 2 h, increasing to 84.8–90.0% after 8 h and reaching 96% after 24 h. Solid-state analyses indicated complete amorphization of the drug in these microparticles. The spray-drying temperature affected process efficiency but did not significantly impacted morphology or dissolution behavior. The optimized MODTs disintegrated in less than 30 s and had a tensile strength of up to 2.62 MPa. Importantly, compression increased the initial BF release from 26.4% for the microparticles to 43.9% for the MODTs at 0.5 h, resulting in f₂ values of 45.04–48.46. Despite the higher initial BF release, the moderately prolonged-release profile was maintained in the case of MODTs. Conclusions: These findings demonstrate the feasibility of combining prolonged-release microparticles with orodispersible minitablets as a proof-of-concept for a pediatric drug delivery approach. Full article

Background: Malaria is a significant public health challenge in the Democratic Republic of the Congo. In conflict-affected areas, access to quality-assured ACTs is restricted by chronic stockouts and circulation of substandard and falsified antimalarials. This study investigates perceptions and social acceptability of Artemisia annua herbal tea in the Kalima Health Zone. Methods: Distinct from the prior provider-arm cross-sectional survey of the same program in the Kalima Health Zone which sampled only biomedical healthcare workers (n = 337), this exploratory qualitative study adopted a socio-anthropological design across three stakeholder strata (community users, biomedical providers, opinion leaders). Maximum-variation purposive sampling recruited 30 informants across five health areas (11 end-users, 11 providers, 8 opinion leaders). Sample-size adequacy was assessed against Malterud’s information power framework; data collection continued until operational thematic saturation. Hybrid inductive–deductive thematic content analysis followed COREQ reporting. Results: End-users demonstrated high willingness, driven by accessibility, perceived three-day recovery, and avoidance of unreliable ACTs. Biomedical providers voiced intense posological anxieties over uncalibrated raw biomass and sub-therapeutic dosing. Behavioral patterns were shaped by socio-religious norms and digitally mediated religious discourse. A unanimous demand for industrial galenic transformation of raw biomass into calibrated tablets emerged across all groups. Conclusions: This study does not validate the clinical efficacy, safety, posological adequacy, or resistance-attenuation potential of Artemisia annua herbal tea. It documents a transversal household-level consensus, across the three strata and five health areas, that Artemisia annua herbal tea adoption responds to documented double ACT supply chain failure. A unanimous demand for industrial galenic transformation emerged across all stakeholder groups. Full article

Objectives: Fixed-dose combination tablets containing sitagliptin hydrochloride (SG) and metformin hydrochloride (MF) are a mainstay in the clinical management of type 2 diabetes. However, SG is highly susceptible to chemical degradation during storage, particularly in the presence of MF. Herein, a bilayer tablet in which SG and MF are physically separated into distinct layers was designed to enhance the chemical stability of SG while ensuring pharmacokinetic equivalence to the marketed reference product Janumet^®. Methods: The compositions of individual SG and MF compartments were selected based on evaluations of their physical properties and dissolution profiles. Critical process parameters, including the pre- and main compression forces and coating levels of bilayer tablets, were fine-tuned to achieve dissolution characteristics comparable to those of the reference product. Results: Under accelerated storage conditions (40 °C, 75% relative humidity), the optimized bilayer tablet exhibited superior stability, with total SG-related impurity levels of 0.18% compared with 0.86% in the reference product after six months. Furthermore, in a randomized bioequivalence study in healthy volunteers (n = 30), the SG/MF bilayer tablet was pharmacokinetically equivalent to the reference product, with all parameters falling within the Food and Drug Administration-mandated regulatory criteria. Conclusions: In conclusion, this SG/MF bilayer tablet has better storage stability than the reference product and may be an alternative to conventional SG/MF combination tablets. Full article

Background: Three-dimensional printing (3DP) is rapidly advancing personalised medicine, yet systematic performance comparison with conventional manufacturing remains limited, particularly for plant-based formulations. Methods: This study compared tablets containing plant-based APIs (cannabidiol, apigenin, and luteolin) produced via conventional hot moulding and semi-solid extrusion (SSE) 3DP. The formulations were evaluated for physicochemical, mechanical, rheological, structural, and drug-release properties. Results: Both manufacturing methods produced tablets with comparable dimensions and mass; however, pronounced formulation-dependent differences were observed in mechanical strength, rheology, and microstructure. The molecular modelling predictions were consistent with the experimental findings. Agar–pectin exhibited the strongest predicted polymer–polymer and polymer–API interactions, including multiple hydrogen bonds, and formed a comparatively dense and cohesive matrix associated with slower API release. In contrast, the weaker interactions predicted for gelatine–pectin were associated with a less cohesive and more porous matrix that facilitated medium penetration, API diffusion, and drug release. SSE printlets generally exhibited greater porosity and more heterogeneous internal architectures than moulded tablets, resulting in enhanced drug release of approximately 95%. Micro-CT analysis provided important structural confirmation; API incorporation increased the void volume of gelatine–pectin printlets from 1.15% to 8.77%, demonstrating that disruption of polymer interactions contributed to pore formation and enhanced molecular diffusion. The observed release behaviour correlated with predicted molecular interactions and experimentally observed microstructural features, where increased porosity and weaker polymer–API interactions facilitated enhanced drug diffusion. Conclusions: Overall, SSE-3DP outperformed conventional moulding, demonstrating superior tunability and performance. This work provides a mechanistically informed strategy for designing plant-based, personalised natural products using 3DP technologies. Full article

Background: Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used for pain, inflammation, and fever. Although many NSAIDs are available without a prescription, inappropriate use may increase the risk of renal, gastrointestinal, and cardiovascular complications. This study evaluated NSAID dispensing patterns and potential risk practices in community pharmacies in the Eastern Province of Saudi Arabia. Methods: A cross-sectional study was conducted in 90 community pharmacies across Al-Ahsa, Al-Dammam, and Jubail Industrial City between February and March 2025. Data on demographics, NSAID type, indication, dosage, frequency, duration, and concomitant medication use were collected and analyzed descriptively. Results: Among the 171 documented NSAID dispensing cases, 98 (57.3%) occurred without a prescription, whereas 73 (42.7%) involved prescription-based dispensing. Ibuprofen (62%) and diclofenac (36.3%) were the most commonly dispensed agents, with oral tablets being the preferred formulation (76.6%). Most documented treatment durations were short (3–7 days) with once- or twice-daily dosing. Common documented indications included dental conditions, pain, and inflammation, although the indication was not specified in 57.3% of cases. At least one potential interaction was identified in 11(7.8%, 95% CI 4.4–13.4%) of the 141 cases with concomitant medication use, corresponding to 13 (5.9%, 95% CI 3.5–9.9%) potential interaction pairs. Conclusions: Frequent non-prescription NSAID dispensing, incomplete documentation, and potentially clinically relevant drug interactions highlight the need to strengthen medication review, documentation, public awareness, regulatory oversight, and pharmacist counseling in community pharmacy practice. Full article

Background/Objectives: Oral solid dosage forms of traditional Chinese and ethnic medicines are currently undergoing modernisation. The objective of this study is to explore the scope for formulation variation arising from batch-to-batch fluctuations in intermediates, and to identify the factors influencing key quality attributes of honey-containing tablets. In this regard, a machine-learning-based predictive model is being formulated that will integrate and analyse formulation factors and the results characterised by the SeDeM expert system. Utilising the SeDeM index as a mediating variable, the study endeavours to establish a comprehensible and predictable stepwise research pathway to provide a foundation for industrial-scale upscaling. Methods: Twelve SeDeM expert systems were utilised to characterise honey-containing granules for formulation screening, to evaluate their suitability for use in traditional Chinese medicine honey-containing tablet systems, and to identify key limiting factors and the feasibility space affecting the quality of the final product; Based on the QBD philosophy, a TriAD (Tri-criterion Adaptive Design) design scheme was proposed, integrating the horizontal balance of orthogonal designs, the spatial coverage of uniform designs, and the parameter estimation efficiency of D-optimal designs into the experimental layout of the formulation feasibility space; Through further data aggregation, a multi-layer feature set comprising four formulation factors, six SeDeM indicators, and three critical quality attributes (CQAs) was constructed. The mediating effects of the SeDeM indicators were revealed through different pathways involving 37 combinations of simple, linear, and Bootstrap models. Furthermore, 180 linear and non-linear machine learning models (comprising 12 categories of algorithms) were trained to predict formulation and CQA outcomes, ultimately completing the design space mapping and validation. Results: The results show that the SeDeM parameters effectively bridge the CQA results of different honey formulations, with these indicators acting as selective mediators between formulation factors and CQAs. Compared with a pure data model relying solely on raw formulation variables, the introduction of SeDeM knowledge, combined with high-information-content samples obtained via TriAD, improved the predictive performance and robustness of the SeDeM–ML hybrid model in terms of disintegration time and hardness; its R²_LOO increased by 0.267 and 0.510, respectively, and the overall predictive space was significantly expanded. Experimental validation was conducted using formulations within the design space predicted by the optimal model; the results showed that both the prediction bias and the relative standard deviation were less than 5 percent. Conclusions: The present study demonstrates that SeDeM can not only be used to evaluate formulations of honey-containing TCM tablets but also serves as an intermediary bridge linking formulation factors, granule-mechanism variables, and tablet quality outcomes. TriAD, in turn, further translates the QbD philosophy into an actionable formulation space design, thereby providing a development pathway for honey-containing tablets that combines interpretability, predictability, and QbD consistency, and offers new insights for the industrial application of oral TCM preparations. Full article

Background: The Biopharmaceutics Classification System (BCS) classifies drug substances according to their aqueous solubility and intestinal permeability; however, its application to veterinary drugs should account for species-specific gastrointestinal physiology. Grapiprant is a selective prostaglandin E₂ receptor subtype 4 (EP4) antagonist approved as an oral tablet to control pain and inflammation associated with osteoarthritis in dogs, but its properties within the BCS framework remain unclear. Methods: This study evaluated the equilibrium solubility of grapiprant across pH conditions relevant to the canine gastrointestinal tract and calculated the dose number (D₀) based on different gastric fluid volumes. A Caco-2 cell monolayer model was used to assess grapiprant intestinal permeability and the effects of time, concentration, pH, and efflux transporter inhibitors on its transepithelial transport. Results: Grapiprant showed relatively small changes in solubility across the tested pH range. D₀ varied with pH and gastric fluid volume and approached or fell below 1 at larger fluid volumes. In the Caco-2 model, grapiprant showed generally limited apparent absorptive permeability, with permeability varying with pH. Efflux ratios were greater than 1, and verapamil reduced the efflux ratio, suggesting possible P-glycoprotein (P-gp) involvement. Conclusions: These findings suggest that both solubility and apparent intestinal permeability may limit the oral absorption of grapiprant under certain canine-relevant conditions. Accordingly, this study provides a biopharmaceutical characterization of grapiprant within the BCS framework rather than a definitive canine BCS classification, highlighting the importance of considering canine gastrointestinal conditions when interpreting its solubility and permeability. The results may support future optimization of dosing conditions and oral formulations. Full article