Background and purpose: Methyldopa (MDP) and Hydrochlorothiazide (HCTZ) are advised for the treatment of essential hypertension. Electrochemical techniques are used for their determination in biological samples. Experimental approach: This study uses a carbon paste electrode (CPE) modified with MoS2 nanosheets and a nickel-based metal-organic framework (MSN-MOF/CPE sensor) for simultaneous voltammetric detection of MDP and HCTZ. Key results: Electrochemical analysis of the modified electrode revealed that, in comparison to an unmodified CPE, MDP oxidation takes place at about 100 mV lower potentials under ideal conditions. With a limit of detection (LOD) of 0.01 μM, the sensor shows a sensitive response to MDP in the range of 0.05 to 260.0 μM. Additionally, the MSN-MOF/CPE sensor showed high sensitivity for the simultaneous determination of MDP and HCTZ. The defined and separated oxidation peaks of a mixture of MDP and HCTZ showed significant peak potential differences of 240 mV. Conclusion: Ultimately, the suggested method was effectively used to determine MDP and HCTZ in pharmaceutical samples and urine as real samples.
Background and purpose: 5‑fluorouracil (5‑FU) is a widely used antimetabolite chemotherapeutic agent. However, it has substantial cytotoxicity and may cause serious adverse effects, including gastrointestinal toxicity, myelosuppression, and, less commonly, cardiac and neurologic toxicity. To achieve sustained release and reduce systemic exposure and administration frequency, 5-FU can be microencapsulated in biodegradable, non-toxic polyhydroxyalkanoate matrices. Experimental approach: In this research, 5-FU-loaded poly(3-hydroxybutyrate) (P3HB) and poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (P3HBV) micro- and nanoparticles were prepared via spray drying and single emulsion solvent evaporation methods. The obtained particles were characterized in terms of their average hydrodynamic size, zeta potential, surface morphology, drug loading, encapsulation efficiency, release patterns, hemolytic activity, and cytotoxicity to HeLa cervical cancer cells. Key results: The obtained 5-FU-loaded micro- and nanoparticles had a regular spherical shape without surface defects. The nanoparticles were nearly identical in size regardless of the presence of 5‑FU. In contrast, the encapsulation of 5‑FU into microparticles by spray drying caused measurable increases in particle size, with the average hydrodynamic diameter increasing by 21.0 % for P3HB and by 28.6 % for P3HBV. Although the single emulsion solvent evaporation technique did not achieve therapeutically relevant 5‑FU loading, spray-dried microparticles showed satisfactory drug loading and sustained release of 5-FU over 48 h. The microparticles exhibited pronounced cytotoxicity against HeLa cervical cancer cells while demonstrating lower hemolytic activity than free 5‑FU. Conclusion: In this study, the promising drug-loaded systems based on polyhydroxyalkanoate microparticles were prepared and characterized for sustained 5-FU delivery in the therapy of cervical cancer.
Background and purpose: Quality by design (QbD) has revolutionized pharmaceutical development by shifting from a conventional quality-by-testing approach to a science-based approach that incorporates quality into products and processes from inception. The integration of artificial intelligence (AI), machine learning (ML), automation, and digital technologies with QbD offers new opportunities to enhance process understanding, optimize critical quality attributes (CQAs) and support the Pharma 4.0 industry framework. Experimental approach: A systematic review of studies published between 2016 and 2025 was conducted to evaluate the application of supervised learning algorithms, deep neural networks, reinforcement learning, and digital twin technologies within QbD. Regulatory frameworks, including International Council for Harmonisation (ICH) quality guideline Q8 through Q14, the U.S. Food and Drug Administration’s Emerging Technology Program and the European Medicines Agency quality initiative, together with representative industrial case studies, were also examined. Key results: This review demonstrates that AI-driven QbD improves process understanding, CQA optimization, batch-to-batch consistency, process robustness, and real-time quality control. Further, advanced computational models enable predictive process monitoring, intelligent decision-making, and in silico experimentation, reducing manufacturing costs, development time and experimental burden. However, challenges related to data quality, model interpretability, validation, and regulatory harmonisation remain a critical barrier to widespread implementation. Conclusion: The convergence of AI, ML and QbD provides a robust framework for intelligent pharmaceutical manufacturing (PM). AI-enabled QbD supports the development of high-quality products through predictive, data-driven, and in silico approaches while accelerating development and improving manufacturing efficiency. These technologies offer a practical roadmap toward Pharma 4.0 and the future of digital PM.
Background and purpose: The simultaneous determination of acetaminophen (ACE) and ciprofloxacin (CIP) is of considerable importance for pharmaceutical quality control, necessitating the development of sensitive and reliable electrochemical sensors. In this study, a holmium-modified UiO-66 metal-organic framework (Ho/UiO-66) was synthesized and evaluated as an electrode modifier for the simultaneous electrochemical determination of ACE and CIP. Experimental approach: Ho/UiO-66 was synthesized via a solvothermal method and characterized by X-ray diffraction, Fourier-transform infrared spectroscopy, Raman spectroscopy, nitrogen adsorption-desorption analysis, scanning electron microscopy, transmission electron microscopy and energy-dispersive X-ray mapping. The electrochemical behaviour of ACE and CIP at the Ho/UiO-66-modified glassy carbon electrode (Ho/UiO-66/GCE) was investigated using cyclic voltammetry and differential pulse voltammetry. The effects of solution pH, scan rate, accumulation potential, and accumulation time were systematically optimized. Key results: The characterization results demonstrated the successful incorporation of Ho species while preserving the crystalline structure of UiO-66. Among the investigated materials, Ho/UiO-66 (3/100 molar ratio) exhibited the most favourable combination of crystallinity, porosity and electrochemical performance, and was therefore selected for sensor fabrication. Under the optimized conditions, well-resolved oxidation peaks for ACE and CIP were obtained, enabling their simultaneous determination without mutual interference. The oxidation processes were found to be predominantly diffusion-controlled. The developed sensor exhibited satisfactory analytical performance with wide linear concentration ranges, low detection limits, satisfactory repeatability, reproducibility, and long-term stability. The sensor was applied to the determination of ACE and CIP in real pharmaceutical samples with satisfactory recoveries. The analytical results showed good agreement with those obtained using the reference high-performance liquid chromatography method. Conclusion: The proposed Ho/UiO-66/GCE sensor provides a reliable and practical platform for the simultaneous electrochemical determination of ACE and CIP, demonstrating its potential applicability for pharmaceutical analysis.
Background and purpose: Erlotinib (ERL), a first-generation epidermal growth factor receptor tyrosine kinase inhibitor drug that is used in non-small cell lung cancer treatment, requires precise therapeutic drug monitoring owing to its narrow therapeutic window and significant inter-patient pharmacokinetic variability; existing chromatographic methods, while robust, are resource-intensive and incompatible with point-of-care settings, necessitating the development of simpler, cost-effective electroanalytical alternatives. Experimental approach: A titanium dioxide nanoparticle-modified screen-printed electrode (TiO₂NP@SPE) was fabricated via a facile single-step modification and comprehensively characterized by scanning electron microscopy - energy dispersive X-ray Analysis, Fourier transform infrared spectroscopy, X-ray diffraction and electrochemical impedance spectroscopy; electrochemical performance was evaluated by cyclic voltammetry and differential pulse voltammetry, and analytical validation was performed in human serum using the standard addition method. Key results: The TiO₂NP@SPE demonstrated markedly enhanced electron transfer kinetics over the bare SPE, yielding a well-defined linear response with a competitive limit of detection, high sensitivity, and intra- and inter-day serum recoveries within acceptable precision limits, alongside excellent selectivity against physiologically relevant interferents and structurally related anticancer agents. Conclusion: This work developed a disposable screen-printed electrode sufficient to achieve sensitive, selective, and accurate quantification of ERL in human serum using TiO₂NP@SPE as a promising, clinically translatable platform for point-of-care therapeutic drug monitoring in oncology; future efforts should address the elevated detection limit relative to the bare electrode and extend validation to real patient plasma samples to fully confirm clinical applicability.
