Search Results (452)

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: 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. Full article

Oral diseases cause a wide range of difficulties for patients. The natural bioactive compound dihydroquercetin (DHQ), which demonstrates regenerative, anti-inflammatory, antioxidative, and antibacterial effects, is of interest for their treatment. The combination of DHQ and l-lysine DHQ is “very easily soluble”. The aim of this study is to compare orally disintegrating tablets based on raw DHQ and on the DHQ-l-lysine composition. Following the guidelines outlined in the ICH Q8 (R2) standard, a fundamental quality target product profile and critical quality attributes were established. The Sediment Delivery Model (SeDeM) method was used to evaluate the substance suitability for direct compression. Quantitative analysis of the DHQ release was carried out by high-performance liquid chromatography, and infrared (IR) spectroscopy was performed using the attenuated total reflection technique without any prior sample preparation. The DHQ-l-lysine composition shows improved dimensions (4.12) and flowability (4.96). The release rate constants (K_release) were 8.14 and 3.61%/min, while the half-release periods (t_50%) were 6.14 and 13.85 min for tablets with DHQ (TF1) and DHQ-l-lysine compositions (TF2), respectively. The difference factor (f₁) and similarity factor (f₂) were 23.43% and 43.37%, respectively. The tablet manufacture had a critical impact on the characteristics of the IR spectra (the r values −0.8785 and 0.5474 for TF1 and TF2). The conducted study demonstrates the promise of using DHQ-l-lysine composition for developing effective dosage forms with improved technological characteristics and controlled release of the active substance. Full article

Vitamin B6 is a coenzyme involved in more than 150 biochemical reactions in the body. Its intake has favorable effects for many diseases like Parkinson’s disease, glaucoma, and endometriosis. Vitamin B6 can be obtained from tablets, aqua vitamin, and a variety of food sources, including meat, fish, and vegetables. There is a need for process analytical control for fast, ultrasensitive, and selective methods of determination of vitamin B6 in order to produce drugs of high pharmaceutical purity. Also, the on-site determination of vitamin B6 in vegetables can contribute to the fast, real-time control of the quality of vegetables. Therefore, a fast ultrasensitive sensing strip based on the immobilization of heptakis(2,3,6-tri-O-methyl)-beta-cyclodextrin on a matrix containing single-walled carbon nanotubes was constructed and used for on-site pharmaceutical process control of vitamin B6, as well as for on-site quality control of food. The sensing strip provided two linear concentration ranges: the first one between 1.69 × 10⁻¹⁵ and 1.69 × 10⁻⁵ g mL⁻¹ with a sensitivity of 6.96 × 10⁴ s⁻¹ g⁻¹ mL, and the second one between 1.69 × 10⁻⁵ and 1.69 × 10⁻³ g mL⁻¹ with a sensitivity of 3.65 × 10² s⁻¹ g⁻¹ mL. The limit of quantification was 1.69 fg mL⁻¹. A % recovery higher than 94.50% was determined for Vitamin B6 in tablets, aqua vitamin, and avocado, with % relative standard deviations lower than 1.00%. A lower determination limit was obtained when the sensing strip was used for the assay of vitamin B6 in different samples compared with other methods used to date for its assay. Also, the results of the analysis were obtained faster, in real time, compared with other methods for which a long sample processing time is needed before analysis. Full article

Background/Objectives: Tirzepatide is a dual GIP and GLP-1 receptor agonist indicated for the treatment of type 2 diabetes and obesity. Oral delivery of tirzepatide is limited by poor gastrointestinal permeability, pH-dependent solubility, and manufacturing challenges associated with high-dose absorption enhancers. Methods: This study developed an immediate-release oral tirzepatide tablet using a Quality by Design (QbD) approach. Sodium caprate (C10) was selected as the absorption enhancer based on acid-neutralizing capacity, Caco-2 permeability enhancement, and preliminary rat pharmacokinetic screening. Quality target product profile, critical quality attributes, preliminary hazard analysis, and failure mode and effects analysis identified binder/disintegrant ratios as critical material attributes and hammer milling conditions as critical process parameters. Face-centered central composite designs and multiple-response optimization (MRO) were applied to optimize dissolution, flowability, and tablet mechanical integrity. Results: The optimized binder/disintegrant composition produced benchmark-comparable dissolution profiles against oral semaglutide tablets in pH 1.2, 4.0, and 6.8 media, with f₂ values exceeding 50 for both C10 300 mg and 500 mg formulations. The optimized process yielded tablets with low friability (0.58%) and acceptable flowability (Carr’s index, 24). In beagle dogs, the C10 300 mg formulation achieved higher systemic exposure than the C10 500 mg formulation, with a C_max of 46.49 ± 23.79 ng/mL and AUC_last of 1261.03 ± 690.44 h·ng/mL. Conclusions: These results support C10-mediated oral tirzepatide delivery and QbD-based optimization for oral peptide tablets. Full article

Background/Objectives: Direct compression of cohesive powders is often challenged by poor flow, blend heterogeneity, and variable tablet quality. This study investigated how mixing time, fill level, and rotational speed affect the blending behavior and tablet properties of a sodium naproxen–calcium carbonate formulation and aimed to define a robust operating space for process optimization. Methods: Powder blends were prepared in a V-type mixer according to a central composite design and analyzed using response surface methodology. The effects of the three process parameters were evaluated through powder flow descriptors (angle of repose, angle of fall, and angle of difference) and tablet quality attributes, including thickness, mass, active pharmaceutical ingredient (API) content, and abrasiveness. Statistical significance was assessed by ANOVA, and a design space was established using predefined acceptance criteria. Results: Mixing time significantly affected the angle of difference, indicating changes in blend cohesiveness and flow uniformity, whereas fill level significantly influenced API content. Tablet thickness and mass remained relatively stable across the tested conditions. Abrasiveness showed the greatest numerical variability and tended to increase at high fill levels combined with short mixing times. Response surface analysis identified two acceptable operational regions that satisfied the quality criteria for blend homogeneity, API content, and abrasiveness. Conclusions: The studied process variables exerted selective, property-specific effects rather than uniform changes across all quality attributes. The results support QbD-based process design for cohesive direct-compression systems and show that robust tablet manufacture can be achieved within more than one operating window. Full article

Paracetamol (PA) ranks among the most frequently prescribed over-the-counter analgesic and antipyretic agents worldwide; nonetheless, overdose scenarios are associated with severe hepatotoxic and nephrotoxic consequences, while its incomplete metabolic removal renders it a persistent micropollutant in surface and wastewater systems. These concerns underscore the urgent need for rapid, cost-efficient, and highly sensitive analytical tools capable of quantifying PA at trace levels in complex matrices. In the present study, spherical gold nanoparticles (AuNPs) were fabricated through an environmentally benign route exploiting an aqueous extract of Juniperus sp. leaves as the reducing and capping agent, with polyvinylpyrrolidone (PVP) serving as an additional colloidal stabilizer. The resulting nanoparticles were immobilized on a glassy carbon electrode to construct an AuNPs/PVP/GCE sensing platform. Physicochemical characterization by UV–Vis spectroscopy, dynamic light scattering (DLS), and transmission electron microscopy (TEM) verified the spherical morphology, narrow size distribution, and colloidal stability of the synthesized AuNPs, and further confirmed a 3.5-fold enlargement of the electroactive surface area relative to the unmodified electrode. Under fully optimized conditions, the fabricated sensor delivered a well-defined linear voltammetric response toward PA oxidation across the concentration interval of 0.05–0.31 µM (R² = 0.9939), with a limit of detection of 0.024 µM and a limit of quantification of 0.080 µM. The sensor retained its analytical accuracy in the presence of common co-existing species, including ascorbic acid, uric acid, dopamine, caffeine, ibuprofen, and adrenaline. Quantitative determination of PA in commercial tablet formulations via the standard addition approach yielded results in close agreement with the declared content, confirming the practical suitability of the AuNPs/PVP/GCE platform for routine pharmaceutical quality control. Full article

Emissivity is a parameter allowing the assessment of thermal/optical properties of active pharmaceutical ingredients (APIs). ε reflects radiative properties, changes with product aging, and correlates with surface characteristics. This study analyzed the thermal emissivity of commercial tablets—extended-release tablets with metformin hydrochloride (from two manufacturers: XR I and XR II), coated (Co) tablets with ibuprofen, and chewable (Ch) tablets with sodium aluminum dihydroxycarbonate—and compared unexpired vs. expired products. We used the ET 100 emissometer (Surface Optics Corporation, USA; IR range 1.5–21 µm) to measure directional–hemispherical reflectance (DHR) at 300 K, and on the basis of these values, directional thermal emissivity at 20° (DTE20) and 60° (DTE60) and hemispherical thermal emissivity (HTE) were calculated. Then, emissivity parameters were evaluated at 500 K, 800 K, and 1200 K. The DHR values at a 60° angle differed between unexpired and expired XR II tablets across all spectral bands and for XR I tablets, except in the 3.0–4.0 micron range. In turn, for DHR at 20°, high effect sizes were demonstrated between unexpired and expired Ch tablets for 1.5–2.0, 2.0–3.5, 4.0–5.0, and 5.0–10.5 microns. For the DHR at 60°, the high effect size between unexpired and expired Ch tablets was found at 1.5–2.0, 2.0–3.5, and 4.0–5.0 microns. At 300 K, XR I and XR II tablets showed comparable DTE20, DTE60, and HTE. The Ch tablets had higher DTE20 than XR I and XR II (0.968 vs. 0.954 and 0.958, respectively; p < 0.001) and Co tablets (0.968 vs. 0.930; p < 0.001). The Co tablets had the highest DTE60 mean values (0.941 vs. 0.926 for Ch, p < 0.001; 0.926 for XR I, p < 0.001; 0.932 for XR II, p = 0.001). The HTE value was the highest for Ch tablets (p < 0.001 vs. others). During thermal modeling of the emissivity parameters, all DTE20, DTE60, and HTE values decreased with temperature, reaching their lowest values at 1200 K. The largest relative decrease in HTE values (over 15%) between the standard measurement temperature of 300 K and the modeled temperature of 1200 K was found for Ch tablets. Tablets with different release profiles show distinct DTE20, DTE60, and HTE values, suggesting that emissivity may serve as a rapid, non-destructive screening tool that could support further pharmaceutical evaluation during storage. However, emissivity alone does not establish pharmaceutical quality, and the present findings should be interpreted as proof-of-concept rather than as validation of a stand-alone quality-control method. Full article

The growing environmental crisis, particularly water pollution from detergents, necessitates a shift from reactive compliance to proactive eco-innovation, as current methods often fail to systematically resolve trade-offs between performance, safety, and ecology. This study develops and illustrates the application of the Evolutionary-Driven Design Framework (EDDF), an integrated methodology that combines PESTEL analysis, historical evolutionary pattern analysis, Quality Function Deployment (QFD) with a novel contradiction index, Theory of Inventive Problem Solving (TRIZ), and environmental assessment. The framework was applied to redesign a conventional laundry detergent with the objectives of zero phosphates, superior biodegradability (>85%), maintained efficacy, and controlled cost. The quantitative contradiction index matrix prioritized critical unsustainable parameters (e.g., EDTA, Cocamide DEA) for substitution over mere optimization. Through an iterative feedback loop, the process evolved from a biobased concentrate to an “enzymatic power tablet” (Concept B). This waterless, solid formulation uses sodium citrate as a biodegradable builder and an encapsulated multi-enzyme system, achieving an estimated >90% biodegradability and zero phosphates while meeting technical and economic targets. The EDDF provides a structured, anticipatory roadmap that transforms regulatory and market pressures into drivers of innovation, offering companies a promising method for designing sustainable products by proactively resolving contradictions and avoiding historical mistakes. Full article

Background/Objectives: Despite hematoxylin and eosin (H&E) staining remaining the cornerstone of histopathological diagnosis, substantial intra- and inter-laboratory variability persists. This issue is increasingly relevant in Digital Pathology, where staining inconsistency may affect whole-slide image interpretation and the performance of image analysis algorithms. In the present work, we evaluated the diagnostic adequacy and non-inferiority of a novel tabs-based H&E histochemical staining method compared with conventional liquid reagents. Methods: Fifty formalin-fixed paraffin-embedded tissue samples from routine practice were sectioned in duplicate and stained either conventionally or using H&E Stain Tabs. After slide review, 14 representative tissue samples were selected, scanned at 40× magnification, and used to generate 24 matched image pairs at different magnifications. A blind online survey was completed by 13 expert pathologists using high-quality monitors. Participants assessed overall staining preference and rated stromal, epithelial, cytoplasmic, and nuclear staining quality. Non-inferiority was tested using a predefined margin of −0.10, and paired rating differences were analyzed using the Wilcoxon signed-rank test. Results: Across 312 paired evaluations, the tabs-based method was preferred in 120 cases (38.5%), conventional staining in 118 cases (37.8%), and no preference was expressed in 74 cases (23.7%). The tabs-based method met the criterion for non-inferiority compared with standard staining (z = 2.7). Rating-scale analysis showed significantly better stromal evaluation with the tablet-based method (z = 2.638; p = 0.008), whereas no significant differences were observed for epithelial, cytoplasmic, or nuclear staining. All evaluated images were considered diagnostically adequate. Conclusions: The tabs-based H&E stain was non-inferior to the conventional method and showed particularly favorable performance in the assessment of stromal components. These findings support its potential role in improving staining reproducibility and standardization, particularly in Digital Pathology workflows where pre-analytical and analytical consistency is critical. Full article

In recent years, the touch panel industry has experienced rapid growth. With technological maturation and progressive cost reduction, touch technology has been widely adopted in human–machine interfaces. Currently, touch panels are predominantly employed in smartphones and tablet devices, and the industry is increasingly pursuing thinner, lighter designs, driving the development of diverse touch technologies, including one-glass solution (OGS), on-cell, and in-cell architectures. To enhance competitive advantage within the touch panel industry, it is essential to improve production efficiency and elevate product quality; consequently, yield has become a critical metric for evaluating industrial competitiveness. This study adopts the electrical test yield of Touch-on-Lens (TOL) touch-sensing glass as the primary performance indicator. A Six Sigma DMAIC (Define, Measure, Analyze, Improve, Control) framework is applied to systematically address impedance-related quality defects occurring during manufacturing. First, key quality characteristics (KQCs) of the TOL touch-sensing glass process are rigorously defined. Subsequently, measurement system analysis (MSA) and process capability assessment are conducted. Next, the Taguchi method is employed to identify the most influential process factors affecting electrical test yield. Finally, response surface methodology (RSM) is utilized to determine the optimal combination of process parameter settings that maximize electrical test yield. Results from the empirical case study demonstrate that the electrical test yield improved significantly—from 90.2% to 93.6%. This outcome validates that the integrated application of the Six Sigma DMAIC methodology, combined with the Taguchi method and RSM, effectively enhances the electrical test yield of TOL sensing glass. The proposed approach offers a robust, data-driven improvement framework applicable to touch panel manufacturers seeking to optimize sensing-glass fabrication processes—thereby supporting broader industry efforts to improve product quality and reduce manufacturing costs. Full article

Botanical insecticides represent a promising alternative to synthetic chemicals for controlling stored-grain pests. However, their use is limited by formulation-related challenges that affect grain quality. This study conducted a comparative evaluation of the insecticidal effectiveness of Artemisia herba-alba crude extract and a solidified matrix formulation (Tablet-like formulation), against Sitophilus oryzae. The formulation involved embedding the extract in a cellulose–starch base. The evaluation included insect mortality, repellency behavior, oxygen consumption, and selected biochemical parameters. Chemical profiles were analyzed using gas chromatography–mass spectrometry (GC–MS). The crude extract demonstrated strong insecticidal activity, achieving 100% mortality at 10,000 ppm after 72 h. In contrast, the tablet-like formulation showed reduced mortality (33%) under the same conditions. Similar trends were observed in repellency tests, with the crude extract showing higher immediate activity (100%) compared to the tablet formulation (67.44%). Both treatments significantly decreased oxygen consumption and levels of lipase, α-amylase, and neuropeptide F. Only the crude extract affected protease and monoamine oxidase activities. GC–MS analysis revealed that, despite variations in the number and relative abundances of compounds detected, both formulations shared several major constituents. In sum, the crude extract showed superior performance in several parameters, particularly in rapid activity, while both forms exhibited comparable effects in other responses. These findings indicate that the intended application should guide formulation selection, with the crude extract is more suitable for rapid pest control, while the tablet-like formulation may be better for long-term protection and preservation of grain quality during storage. Full article

Dietary fibre deficiency remains a global nutritional concern, and the development of fibre-enriched functional foods is increasingly important. Fruit processing by-products, such as pomelo (Citrus maxima) peel, represent a sustainable source of dietary fibre with potential techno-functional applications. In this study, a fibre-enriched chewable tablet was developed using pomelo (Citrus maxima) peel fibre (CPF) as a functional ingredient and structural matrix. The formulation was prepared through direct compression and systematically evaluated in terms of powder flow behaviour, structural characteristics (FTIR, XRD, and SEM), hydration-related functionality, and tablet quality attributes. The CPF-based powder blend exhibited good flowability and compressibility, with an angle of repose of 26.62°, Carr’s index of 8.9%, and a Hausner ratio of 1.22, indicating suitability for tablet processing. Structural characterisation demonstrated the formation of a semi-crystalline matrix with a porous fibrous morphology. CPF incorporation significantly improved water-holding capacity (9.84 g/g) and oil-holding capacity (2.97 g/g), indicating enhanced hydration functionality. The developed tablets exhibited uniform weight (560 ± 9.5 mg), consistent dimensions, and acceptable disintegration behaviour (168 ± 15 s), demonstrating satisfactory physical quality. Overall, these findings suggest that pomelo peel fibre can be effectively utilised in chewable delivery systems, providing a feasible strategy for the valorisation of citrus by-products in functional food applications. Full article

Background/Objectives: Multiple Traffic Light (MTL) front-of-pack (FOP) labels are being considered in Bahrain. We tested whether an adapted MTL label improves the nutritional quality of grocery purchases. Methods: In a two-arm randomized controlled intercept trial (January–May 2025), adults (≥21 years) responsible for household grocery shopping were recruited in high-footfall public venues and asked to complete a one-time shop on a tablet-based, purpose-built online grocery platform. The MTL label was adapted for Arabic reading direction and displayed per-serving nutrients and % recommended daily intake. Treatment effects were estimated using ordinary least squares regressions with robust standard errors and covariate adjustment. Results: Of 395 randomized participants, 360 were included in primary analyses (control n = 183; MTL n = 177). MTL exposure was not associated with a significant change in the primary outcome (basket weighted average MTL score per serving; β = 0.037; p = 0.64) or in per-serving calories and nutrients of concern (all p > 0.17). In the post-shop assessment, only 47.2% of participants correctly interpreted MTL labels, indicating modest objective label comprehension under the study conditions. Conclusions: These findings suggest that the impact of front-of-pack labels likely depends on both implementation features and consumer understanding, and that pairing labels with public communication and nutrition literacy initiatives may be necessary to maximize the effectiveness of labels in Bahrain and the wider Gulf region. Full article

Historically, pharmaceutical formulation development relied heavily on trial-and-error experimentation, which was useful for empirical progress but often provided limited mechanistic understanding and insufficient efficiency for increasingly complex drug products. The introduction of Design of Experiments (DoE) and Quality by Design (QbD) established a more systematic framework for studying formulation variables, manufacturing parameters, and Critical Quality Attributes (CQAs). Approaches such as factorial designs, response-surface methodology, and mixture designs have therefore become central to modern pharmaceutical development because they improve experimental efficiency and support the definition of design space. However, as formulations become more nonlinear, high-dimensional, and multi-objective, these classical approaches may no longer be sufficient on their own. This review examines the evolution of experimental design in pharmaceutical research, from one-factor-at-a-time experimentation to structured DoE/QbD strategies, and then to emerging intelligent optimization methods. Its central objective is to clarify when conventional DoE/QbD remains appropriate and when it should be complemented by machine learning, Bayesian optimization, digital twins, and closed-loop experimental systems. The review first summarizes the foundations and strengths of classical experimental design; then, it discusses its practical limitations in complex formulation settings, and finally evaluates how data-driven and hybrid approaches can extend pharmaceutical development. Evidence from tablets, capsules, nanocarriers, transdermal patches, and biotherapeutic systems suggests that intelligent optimization can improve predictive performance and experimental efficiency when used alongside, rather than instead of, established pharmaceutical development principles. Full article