Search Results (1,766)

Counterfeit and unsafe medicines pose significant risks to patient safety and undermine trust in healthcare systems. This paper presents ACTMeds, a blockchain-supported pharmaceutical traceability and recall platform that considers pharmaceutical supply chain requirements and public health operational needs relevant to the Australian Capital Territory (ACT). The system integrates Ethereum smart contracts, developed using Ganache, with a React-based web application providing regulator, operator, pharmacy, and auditor interfaces, alongside a public verification portal leveraging QR and GS1 barcodes. In addition, role-based access control is enforced across the medicine lifecycle, including manufacture, custody transfer, dispensing, and recall, with immutable on-chain events generated to support auditability and accountability. To balance transparency with confidentiality, the platform prototypes a zero-knowledge (ZK) recall mechanism in which regulators can cryptographically prove that recall conditions meet predefined policy requirements without disclosing sensitive incident details. Threat modeling was conducted using the STRIDE framework, and security evaluation combined static application security testing (Solhint and ESLint) and dynamic testing. The paper further discusses deployment options, cost considerations, ZK recall performance analysis, ethical implications, and future enhancements. Security testing validated the platform’s resilience, with no high-severity vulnerabilities identified and medium-severity issues related to HTTP security headers addressed. The results indicate that a regulator-led, privacy-preserving, tamper-evident ledger can improve medicine authenticity verification and recall responsiveness while maintaining compliance and data protection obligations. Full article

This paper systematically reviews losartan, a hypertension pharmaceutical compound that is one of many newly identified emerging contaminants in water. Worldwide use of pharmaceuticals continues to grow, and losartan has been identified as a contaminant that frequently accumulates in aquatic systems as a result of this global increase in use. The paper presents systematic reviews on the environmental occurrence, physicochemical characteristics, analytical methods of detection, and remediation techniques associated with losartan contamination. Losartan is often detected at levels of ng L⁻¹–µg L⁻¹ in wastewater systems, surface water and marine ecosystems, very effectively demonstrating the inadequacies of existing conventional wastewater treatment facilities, which are typically capable of removing only 20–70% of the contamination, with this variability largely attributed to differences in hydraulic/solids retention times, operational conditions, influent organic load, and the limited microbial acclimatization to recalcitrant pharmaceutical compounds. Emerging remediation technologies demonstrate the potential for removal efficiencies of >90% include hybrid systems, advanced electrochemical processes, new improved adsorption systems, and novel material for adsorption. However, there are still considerable barriers to progress, including excessive energy use, high operating costs, and perhaps most concerning, potentially toxic transition products generated by partial degradation. Furthermore, the literature review identified key literature gaps: lack of specific regulations, absence of full-scale studies, and inconsistencies in by-product toxicity assessments. The conclusion of this review is that to achieve worldwide water security and sustainability of aquatic resources, effective mitigation of the environmental risks associated with losartan requires combined approaches comprising innovative technologies, comprehensive ecotoxicological investigations, and improved collaboration between scientists, policymakers, and industry. Full article

A Fixed-dose combination (FDC) therapy of ezetimibe (EZT) and atorvastatin (ATV) is increasingly prescribed for high-risk hyperlipidemic patients with cardiovascular disease. However, the pharmaceutical production of FDC EZT/ATV tablets often results in poor ATV dissolution under acidic conditions, failing to meet regulatory requirements. This study aimed to improve ATV dissolution in acidic media through nanosuspension (NS) technology and microenvironmental pH modification. The experimental stages included preparation and characterization of ATV-NS, optimization of FDC EZT/ATV-nanocrystal tablets with pH modifiers, and evaluation of dissolution similarity (f₂) against the innovator product Atozet^®. ATV-NS was prepared via sonication and high-pressure homogenization using different stabilizers. Poloxamer 188-stabilized ATV-NS demonstrated optimal stability (particle size: 466.6 ± 8.9 nm; polydispersity index: 0.12 ± 0.10; zeta potential: −44.20 ± 0.06 mV) and significantly enhanced solubility (p < 0.05) compared with pure ATV. FDC EZT/ATV-nanocrystal tablets incorporating pH modifiers achieved f₂ values for ATV of 52.36, 51.31, and 51.09 in NaCl/HCl pH 1.2, acetate buffer pH 4.5, and phosphate buffer pH 6.8, respectively. In contrast, EZT exhibited f₂ values of 18.18, 16.72, and 14.66 (acceptable range: 50–100). Although complete profile similarity was not obtained for EZT, ATV dissolution in acidic media improved significantly (p < 0.05), supporting the feasibility of developing a bioequivalent generic FDC EZT/ATV tablet. Full article

The pharmaceutical development of cannabis-based medicinal products is challenged by significant variability in the quality, composition, and standardization of plant-derived active pharmaceutical ingredients (APIs). In Ukraine, despite recent legislative liberalization, a substantial shortage of standardized raw materials continues to limit the development of innovative dosage forms. This study analyses international practices among API manufacturers to identify technological parameters necessary to overcome domestic market barriers and support the implementation of advanced drug delivery systems. Content analysis was conducted on regulatory documentation, professional literature, and manufacturers’ technical specifications. Candidate evaluation followed predefined inclusion and exclusion criteria. The study assessed compliance with Good Manufacturing Practice (GMP) requirements, extraction and purification technologies, the extent of analytical characterization, and batch-to-batch reproducibility. Purposive sampling enabled a comparative analysis of various technological approaches. Marked heterogeneity was observed in API standardization and analytical control indicators among manufacturers. Possession of a GMP certificate was found necessary but may be insufficient to ensure the pharmaceutical equivalence of materials. Differences in extraction methods and purification levels may affect stability profiles, pharmaceutical development strategies, and risk management related to final product quality. The findings demonstrate that manufacturer selection is a critical decision point in pharmaceutical development, with substantiated supplier choice directly influencing dosage form development and regulatory compliance. Full article

The pharmaceutical industry has seen significant growth in the development of antibody-based therapeutics, especially monoclonal antibodies (mAbs) and bispecific antibodies (bsAbs), used in the treatment of cancer and neurodegenerative diseases. However, their production and purification remain challenging. It is difficult to achieve both high product yield and the strict purity required for clinical use. Downstream processing is expensive and often involves trade-offs between efficiency and product quality. In addition, current purification methods do not fully remove contaminants, especially host cell proteins, residual DNA, and protein aggregates, affecting the safety and effectiveness of the final product. Recent advances in purification technologies, such as improved chromatography techniques and alternative separation methods, have shown promise in addressing some of these limitations. Process optimization and the integration of continuous manufacturing approaches are being explored to enhance efficiency and scalability. Furthermore, increased regulatory expectations are driving the need for more robust and reproducible purification strategies. As the antibody therapeutics market continues to expand, optimizing manufacturing and purification processes is crucial to achieve cost efficiency and large-scale production. This article discusses the main challenges in antibody production and downstream purification, focusing on monoclonal and bispecific antibodies, and compares current strategies to increase yield, improve purity, and reduce contaminants. Full article

Monohalogen-substituted (F-, Cl-, Br-) phenylethylamine derivates are a valuable class of chiral compounds, e.g., for C-C-coupling reactions, which are the basis for multiple pharmaceuticals and resolving agents. Here, the solid phase behavior of the underlying phenylethylamine derivates, especially of the corresponding hydrochloride salts, is highly relevant as those compounds are often applied in enantiopure form during the production processes. In this study, the solid phase behavior of 20 synthesized chiral phenylethylamine hydrochloride derivates (both enantiomers and racemates) was investigated including detailed information regarding melting behavior, powder X-ray diffraction data and the type of the chiral system present. Further, the binary melt phase diagram of a found conglomerate system and two novel enantiomer crystal structures were determined. This study is aimed at revealing structure–phase behavior relationships for the 20 monohalogen-substituted compounds investigated as well as providing basic solid–phase-related data required for later crystallization-based enantioseparation processes. Full article

Marine polymers have attracted a lot of attention as potential alternatives to the traditional animal-derived polymers in pharmaceutical formulation since they are abundant, biocompatible, and versatile in functionality. However, the presence of these materials in dosage-form studies, often in support of proof-of-concept trials, does not mean they are ready to apply as excipients routinely. This review critically evaluates the reasons why three of the most highly researched marine-derived polymers, chitosan, alginate, and carrageenan, continue to encounter significant translational barriers in pharmaceutical excipient development. All three polymers have been demonstrated to have clear pharmaceutical utility; however, their behavior is highly dependent on source, structure, processing history and formulation context. Chitosan explains why functional benefits may be compromised by responses to material requirements; alginate explains why apparent proximity to use may not remove composition-related variability; and carrageenan explains that even seemingly simple rheological functions may be very context-dependent. All of this points to the fact that the major hurdle lies not in the lack of potential, but in the difficulty of achieving the required degree of control, reproducibility, and manufacturability in order to make the reliable use of excipients possible. Future progress in this field will likely require a shift from descriptive exploration toward readiness-focused evidence, including demonstrated control over material attributes, reproducible performance, and feasible qualification pathways. Full article

The resurrection plant Haberlea rhodopensis is a rare species endemic to Greece and Bulgaria, renowned for its exceptional desiccation tolerance and rich phytochemical composition. This study investigated the antioxidant, cytoprotective, and wound-healing-associated effects of H. rhodopensis ethanolic extract (HEE) in human keratinocytes (HaCaT cells) under oxidative and cytotoxic stress conditions. Antioxidant capacity was initially evaluated using a plasmid DNA protection assay, in which HEE attenuated oxidative DNA damage induced by a Fenton reaction system and preserved the native supercoiled structure of pUC19 plasmid DNA. Cytotoxicity screening using the sulforhodamine B (SRB) assay and real-time proliferation monitoring (HoloMonitor^® M4) identified 20 μg/mL as a non-toxic pre-treatment concentration (EC₁₀). Under hydrogen peroxide (H₂O₂)-induced oxidative stress, HEE pre-treatment maintained cell viability and significantly reduced intracellular reactive oxygen species (ROS) levels, indicating a protective effect. In vitro wound-healing assays demonstrated enhanced scratch closure in keratinocyte monolayers. RT-qPCR analysis revealed modulation of antioxidant-related genes (CAT, SOD1, HMOX1, NQO1, GPX, GSR), while mRNA sequencing suggested selective stress-adaptive responses, involving extracellular matrix (ECM)-, metabolic-, and tissue-repair/aging-associated pathways. Overall, HEE exhibits antioxidant and cytoprotective effects in keratinocytes and is associated with transcriptional changes linked to cellular stress responses and wound closure. These findings support its potential relevance for dermatological, pharmaceutical, and cosmeceutical applications, while further studies are required to establish the underlying molecular mechanisms. Full article

The separation of chiral compounds is a challenging issue in various fields, e.g., biochemistry, the pharmaceutical industry, food chemistry, forensics, agriculture, etc. Very often, one of the two enantiomers can exhibit different activity. Therefore, the separation and analysis of enantiomers requires analytical methods for, e.g., quality control, pharmacokinetic studies, etc. Their separation is usually performed by high-performance liquid chromatography (HPLC), gas chromatography, supercritical fluid chromatography and microfluidic techniques such as capillary electrophoresis (CE), nano-liquid chromatography, and capillary electrochromatography (CEC). CEC is a modern analytical technique that combines the features of HPLC and CE (high selectivity and high chromatographic efficiency, respectively). The enantiomers are moved to the detector by an electroosmotic flow generated by the application of high voltage. In this review, the main features of CEC, and the basic principles of enantiomer separation are briefly summarized. Selected applications (appearing 2023–2026 February) employing packed capillaries, and monolithic and open tubular columns, are presented and discussed. Full article

Background: Accurate intraoperative identification of ovarian cancer is challenging, as standard techniques such as visual inspection, palpation, and histopathology often fail to detect microscopic disease. Residual tumor contributes to poor cytoreductive outcomes, high recurrence rates, and chemoresistance. Near-infrared (NIR) imaging using tumor-specific biomarkers has emerged as a promising approach to enhance intraoperative visualization and improve tumor margin delineation. Methods: A focused literature review was conducted using PubMed to identify preclinical and clinical studies evaluating NIR image-guided strategies in ovarian cancer. Studies involving tumor-targeted probes against folate receptor alpha, α3-integrin, mesothelin, and CA125 were included, with emphasis on probe design, delivery, imaging performance, safety, and clinical relevance. Results: Targeted NIR probes consistently demonstrated improved tumor-to-background contrast, higher lesion detection sensitivity, and enhanced intraoperative guidance compared to conventional imaging. Preclinical and early clinical data indicate favorable safety profiles and minimal off-target toxicity. Evidence suggests that NIR-guided surgery may reduce residual disease burden and potentially improve recurrence-free survival. Conclusions: Tumor-specific NIR imaging represents a promising pharmaceutics-based strategy for improving surgical outcomes in ovarian cancer. Despite encouraging results, challenges such as biomarker heterogeneity, limited fluorophore availability, and cost must be addressed. Further large-scale, randomized trials are required to validate efficacy and integrate these approaches into clinical practice. Full article

Concerns about the environmental and health impacts of plasticized poly (vinyl chloride) (PVC), from plasticizer loss to microplastic formation, have created a clear demand to find alternative packaging materials for medical and pharmaceutical use. As a possible polyolefin-based alternative, we blended polypropylene–ethylene copolymers with different ethylene content-controlled phase structures with styrene–ethylene/butylene–styrene block copolymer (SEBS), as modifier. SEBS is elastomeric and performs mechanically like a cross-linked rubber due to its unique microphase-separated morphology of hard spherical polystyrene (PS) domains dispersed in the soft elastomeric ethylene-butylene copolymer (EB) phase. Tests with injection-molded samples and cast films demonstrated promising combinations of flexibility, durability, and transparency—qualities essential for soft medical packaging like infusion pouches and blow–fill–seal bottles. For the desired level of flexibility (reflected by a flexural modulus of 150–250 MPa), blends with two random-heterophasic (RAHECO) copolymers achieved the lower limit with only 15–25 wt.-% SEBS, compared to the 37 wt.-% needed for a single-phase random copolymer (RACO). These blends also exhibited greater toughness and excellent transparency. In contrast, a standard impact copolymer (HECO), with its more crystalline matrix, required a higher modifier content of 45 wt.-% SEBS. Film morphology analysis indicated a gradual shift in disperse phase structure and orientation, leading to phase inversion at the highest SEBS content without negatively affecting transparency. Full article

Background: Non-small cell lung cancer (NSCLC), a malignant tumor with high global incidence and mortality rates, urgently requires more effective targeted drug delivery systems for its treatment. As an EGFR tyrosine kinase inhibitor, gefitinib has its clinical efficacy limited by poor solubility and low bioavailability. This study aimed to develop a gefitinib–salicylic acid salt (Gef-Sa) and its nano-formulation (Gef-Sa-NPs) via a combined strategy of crystal engineering and nanotechnology to improve its pharmaceutical properties. Methods: Gef-Sa was prepared using a suspension method, and its salt formation and thermal stability were predicted by the ΔpKa rule and confirmed by various solid-state characterization techniques, including single crystal/powder X-ray diffraction, thermal analysis, and infrared spectroscopy. Gef-Sa-NPs were prepared via an ultrasound-assisted anti-solvent precipitation method. Their performance was evaluated through in vitro dissolution tests, pharmacokinetic studies, and in vitro antitumor experiments. Results: Gef-Sa-NPs with a particle size of 31 nm (PDI = 0.15) were successfully prepared. In vitro dissolution tests demonstrated that the nano-formulation exhibited a significantly higher dissolution rate in pH 1.2, pH 4.5, pH 6.8 and pure water when compared with the raw drug (p < 0.01). Pharmacokinetic studies revealed that Gef-Sa and Gef-Sa-NPs increased the oral bioavailability in rats to 1.5-fold and 1.9-fold that of the raw drug, respectively. In vitro antitumor experiments confirmed that the Gef-Sa-NPs increased the inhibition rate against A549 cells compared with the Gef. Conclusions: This study innovatively combines salt formation and nanonization technologies to systematically address the key issue of the poor solubility of Gef. The resulting nano-formulation demonstrates excellent dissolution characteristics, pharmacokinetic behavior, and antitumor efficacy. This strategy not only provides a novel drug delivery system with translational potential for NSCLC treatment but also offers a paradigm for the formulation design of poorly soluble drugs. Subsequent research will focus on scaling up production and evaluating pre-clinical safety. Full article

The activated sludge process serves as the core barrier in pharmaceutical wastewater treatment, yet its stability is inherently challenged by the extreme complexity of influent composition and the unpredictability of toxic shocks, particularly under contract development and manufacturing organization (CDMO) operations. Current biotoxicity assessment methods face inherent trade-offs among timeliness, specificity, and matrix robustness, resulting in fragmented, reactive management that lacks predictive capacity. In response, this review critically synthesizes evidence on toxicity pathways and monitoring technologies, systematically evaluating their mechanistic basis and engineering applicability. Building on these findings, we propose a conceptual perception–cognition–response architecture that structures decision-making across three adaptive tiers: (i) a perception layer that tolerates false positives for rapid anomaly detection; (ii) a cognition layer that requires effect-based biological verification; and (iii) a response layer that authorizes resilience-oriented interventions. Rather than a linear pipeline, the three tiers form an adaptive feedback cycle that dynamically aligns monitoring intensity, verification depth, and response authority with real-time risk gradients and site-specific constraints. By explicitly linking biological mechanisms to assessment limitations and tiered decision rules, this review provides a hypothesis-generating roadmap that orients biotoxicity management from episodic, composition-based assessment toward adaptive, effect-driven control. The proposed framework is intended to guide future pilot validation, multi-sensor integration, and context-specific calibration, offering a unified narrative for advancing proactive biotoxicity control in complex pharmaceutical wastewater systems. Full article

Background: Healthcare inventory management is critical for ensuring timely access to supplies and reducing stockouts. As supply chains grow more complex, algorithms, AI, and analytics techniques have emerged as tools for forecasting, tracking, classification, and procurement. Yet empirical validation across diverse contexts remains inadequate, and existing reviews treat these approaches as separate streams rather than an integrated system. Methods: To evaluate these capabilities, a systematic review of 64 peer-reviewed articles published between 2011 and 2025 was conducted using a descriptive and content analysis approach on the use of Triple A (Analytics, AI, and Algorithms) techniques in inventory frameworks across various healthcare contexts, such as hospitals, pharmaceutical supply chains, and humanitarian supply chains. Results: Integrating multiple Triple A approaches consistently outperforms single-method strategies, particularly with RFID and IoT tools. Key findings often overlooked are: emergency procurement and classification, which remain neglected despite the highest patient safety stakes, and key procurement drivers—organizational conditions, supplier reliability, and team capacity. Data quality, interoperability, and cybersecurity further constrain generalizability. Conclusions: Bridging these gaps requires integrated Triple A approaches rather than single methods. Phased implementation, cloud-based platforms, and privacy-by-design offer practical pathways for building resilience under real-world constraints. Full article

Introduction: Depression and anxiety are highly prevalent disorders with a substantial impact on quality of life. Limitations related to the efficacy and tolerability of conventional pharmacological treatments have stimulated increasing interest in complementary therapeutic approaches, including phytotherapy. This review aims to provide an integrative analysis of some plant species present in the spontaneous flora of Romania, correlating their traditional use with the phytochemical, pharmacological, preclinical, and clinical data available globally. The approach aims to highlight the therapeutic relevance of these species in both regional and international contexts. Relevant sections: This narrative review integrates available data on seven species commonly used in traditional medicine: Matricaria chamomilla L., Galium odoratum L., Melissa officinalis L., Leonurus cardiaca L., Hypericum perforatum L., Tilia spp., and Crataegus monogyna Jacq. This review examines their geographical distribution, taxonomic classification, phytochemical composition, proposed mechanisms of action, and available preclinical and clinical evidence, as well as safety considerations and products currently available on the Romanian pharmaceutical sales. Discussion: Current evidence suggests that Hypericum perforatum L. and Melissa officinalis L. are supported by relatively robust clinical data regarding their efficacy in reducing anxiety and depressive symptoms. For the remaining species, evidence is derived mainly from preclinical studies or traditional use. The proposed mechanisms of action include modulation of neurotransmitter activity, antioxidant and anti-inflammatory effects, and regulation of the hypothalamic–pituitary–adrenal (HPA) axis. Conclusions: Phytotherapy represents a promising approach in the management of anxiety and depressive disorders, particularly as a complementary therapeutic option. However, the strength of evidence varies considerably among the analyzed species, and clinical data remain limited for several of them. Future directions: From a future perspective, advancing the clinical relevance of the analyzed plant species requires a more coherent integration of existing pharmacological, preclinical, and emerging clinical data. Particular attention should be given to species for which the current evidence remains predominantly experimental, by promoting research strategies that facilitate the translation of mechanistic findings into clinically meaningful outcomes. Full article