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Drug and Therapeutics Bulletin Jul 2024
Topics: Humans; Fluoroquinolones; Anti-Bacterial Agents; Practice Patterns, Physicians'; Drug Labeling; United States; Drug Prescriptions
PubMed: 38816185
DOI: 10.1136/dtb.2024.000035 -
European Journal of Hospital Pharmacy :... May 2024The use of dose administration aids in automated ward dispensing devices requires the repackaging of medications, which may impact their stability compared with the...
BACKGROUND
The use of dose administration aids in automated ward dispensing devices requires the repackaging of medications, which may impact their stability compared with the original manufacturer's packaging.
OBJECTIVES
This study aimed to assess the physical and chemical stability of clozapine tablets for up to 84 days after repackaging.
METHODS
A total of 900 tablets of clozapine 100 mg (Viatris) were repackaged and stored under five different conditions to conduct physical and chemical stability tests on days 0, 28, 56 and 84. The results were compared with control tablets in their original packaging. Visual inspections of tablet appearance were performed. Physical tests included assessments of mass uniformity, friability and resistance to crushing, following the standards of the European Pharmacopoeia 11th edition. The chemical stability was determined using ultra-high performance liquid chromatography with tandem-mass spectrometry detection (UHPLC-MS/MS) to measure clozapine concentration, N-desmethyl-clozapine, and monitor clozapine degradation to detect formation of any degradation products other than N-desmethyl-clozapine.
RESULTS
Visual examination showed changes in the appearance of tablets only in those stored under UV light. Mass uniformity met standards for all tablets over 84 days. None passed the friability test due to tablet cracking after tumbling. A gradual deterioration in tablet hardness was observed with the resistance to crushing test. In terms of chemical stability, N-desmethyl-clozapine was undetected in any of the tablets stored under all conditions, and the mean concentration of clozapine remained within the target range over 84 days.
CONCLUSION
N-desmethyl-clozapine was not detected and clozapine concentrations remained stable under all storage conditions. The tablets were compliant with the mass uniformity test in each condition. However, the tablets were cracked in the friability test and gradual deterioration in tablet hardness was observed. In the light of these results, the Vinatier Hospital pharmacy has chosen to establish a shelf life for clozapine tablets of 84 days.
PubMed: 38816183
DOI: 10.1136/ejhpharm-2023-004036 -
International Journal of Biological... Jun 2024Carbon dots (CDs) were derived using eggplant peel by a hydrothermal approach and incorporated into the carboxymethyl cellulose (CMC) and gelatin (Gel) blend to develop...
Carbon dots (CDs) were derived using eggplant peel by a hydrothermal approach and incorporated into the carboxymethyl cellulose (CMC) and gelatin (Gel) blend to develop sustainable and functional packaging films for fruit preservation. The CD was uniformly dispersed within the CMC/Gel blend to form a dense and continuous film and fashioned a strong interaction with the polymer chain, increasing the tensile strength of the film by 5.0-16.0 %. Also, with the impregnation of CDs, the UV-blocking potential of the CMC/Gel film was greatly improved to the extent of blocking 94.3 % of UV-B and 72.5 % of UV-A, while the water vapor permeability slightly decreased (by 2.7-5.4 %), and the water contact angle of the film marginally expand (by 6.2-19.1 %). The CMC/Gel film with 3 wt% of CD added depicted strong antioxidant efficacy of 100 % against ABTS and 59.1 % against DPPH and displayed strong antibacterial action that inhibited the progress of Listeria monocytogenes and Escherichia coli by 99.8 %. In addition, when table grapes were packaged using a CMC/Gel composite film containing CD and stored at 4 °C for 24 days, the fruits packed with the composite film maintained excellent external quality and extended the shelf life.
Topics: Gelatin; Carboxymethylcellulose Sodium; Food Packaging; Fruit; Solanum melongena; Carbon; Anti-Bacterial Agents; Antioxidants; Permeability; Listeria monocytogenes; Escherichia coli; Quantum Dots
PubMed: 38815951
DOI: 10.1016/j.ijbiomac.2024.132715 -
Environment International Jun 2024With the discovery of evidence that many endocrine-disrupting chemicals (EDCs) in the environment influence human health, their toxic effects and mechanisms have become...
With the discovery of evidence that many endocrine-disrupting chemicals (EDCs) in the environment influence human health, their toxic effects and mechanisms have become a hot topic of research. However, investigations into their endocrine-disrupting toxicity under combined binary exposure, especially the molecular mechanism of combined effects, have rarely been documented. In this study, two typical EDCs, perfluorooctanoic acid (PFOA) and 4-hydroxybenzophenone (4-HBP), were selected to examine their combined effects and molecular mechanism on MCF-7 cell proliferation at environmentally relevant exposure concentrations. We have successfully established a model to evaluate the binary combined toxic effects of endocrine disruptors, presenting combined effects in a simple and direct way. Results indicated that the combined effect changed from additive to synergistic from 1.25 × 10 M to 4 × 10 M. Metabolomics analyses suggested that exposure to PFOA and 4-HBP caused significant alterations in purine metabolism, arginine, and proline metabolism and had superimposed influences on metabolism. Enhanced combined effects were observed in glycine, serine, and threonine metabolic pathways compared to exposure to PFOS and 4-HBP alone. Additionally, the differentially expressed genes (DEGs) are primarily involved in Biological Processes, especially protein targeting the endoplasmic reticulum, and significantly impact the oxidative phosphorylation and thermogenesis-related KEGG pathway. By integrating metabolome and transcriptome analyses, PFOA and 4-HBP regulate purine metabolism, the TCA cycle, and endoplasmic reticulum protein synthesis in MCF-7 cells via mTORC1, which provides genetic material, protein, and energy for cell proliferation. Furthermore, molecular docking confirmed the ability of PFOA and 4-HBP to stably bind the estrogen receptor, indicating that they have different binding pockets. Collectively, these findings will offer new insights into understanding the mechanisms by which EDCs produce combined toxicity.
Topics: Humans; Caprylates; MCF-7 Cells; Endocrine Disruptors; Fluorocarbons; Cell Proliferation; Parabens; Metabolomics; Multiomics
PubMed: 38815467
DOI: 10.1016/j.envint.2024.108778 -
Therapeutic Innovation & Regulatory... May 2024Technology enabling drug serialisation technology was introduced by regulators to enhance security in pharmaceutical supply chain and protect drugs from infiltration by...
Technology enabling drug serialisation technology was introduced by regulators to enhance security in pharmaceutical supply chain and protect drugs from infiltration by falsified and substandard medicines. The introduction of systems for serialisation required huge financial outlays manufacturers of pharmaceuticals. This study investigated the impact of serialisation on the operational efficiency and productivity in Irish pharmaceutical sites. A qualitative study was conducted with 11 manufacturing sites in Ireland. The participating companies operated a total of 114 pack-lines, representing approximately 65% of the automated packing lines in the country. The study found that serialisation had a negative effect on packaging production line OEE and line availability and on the individuals cost per unit of packaged pharmaceuticals. The research results estimated that the capital costs of serialisation were four times greater than those estimated by the regulators. There was a 4.1 cents average cost per pack for serialisation with high volume sites reporting an annual cost of serialisation of up to €4.5 m per annum and a 2.7% increase in the average cost of goods sold. A pattern whereby where many pharmaceutical manufacturers are transitioning from smaller batch production and moving toward larger batch production sizes in order to increases efficiencies was identified. The research also proposed the use of a serialisation depreciation factor as a method to determine the impact of serialisation on the cost of goods sold. This is the first study of its kind into the cost of serialisation from a manufacturer's viewpoint and studying the effects of serialisation on productivity, line availability and operational efficiency.
PubMed: 38811451
DOI: 10.1007/s43441-024-00662-1 -
Archives of Toxicology Jul 2024Since 2006, the responsible regulatory bodies have proposed five health-based guidance values (HBGV) for bisphenol A (BPA) that differ by a factor of 250,000. This range...
Since 2006, the responsible regulatory bodies have proposed five health-based guidance values (HBGV) for bisphenol A (BPA) that differ by a factor of 250,000. This range of HBGVs covers a considerable part of the range from highly toxic to relatively non-toxic substances. As such heterogeneity of regulatory opinions is a challenge not only for scientific risk assessment but also for all stakeholders, the Senate Commission on Food Safety (SKLM) of the German Research Foundation (DFG) analyzed the reasons for the current discrepancy and used this example to suggest improvements for the process of HBGV recommendations. A key aspect for deriving a HBGV is the selection of appropriate studies that allow the identification of a point of departure (PoD) for risk assessment. In the case of BPA, the HBGV derived in the 2023 EFSA assessment was based on a study that reported an increase of Th17 cells in mice with a benchmark dose lower bound (BMDL) of 0.53 µg/kg bw/day. However, this study does not comply with several criteria that are important for scientific risk assessment: (1) the selected end-point, Th17 cell frequency in the spleen of mice, is insufficiently understood with respect to health outcomes. (2) It is unclear, by which mechanism BPA may cause an increase in Th17 cell frequency. (3) It is unknown, if an increase of Th17 cell frequency in rodents is comparably observed in humans. (4) Toxicokinetics were not addressed. (5) Neither the raw data nor the experimental protocols are available. A further particularly important criterion (6) is independent data confirmation which is not available in the present case. Previous studies using other readouts did not observe immune-related adverse effects such as inflammation, even at doses orders of magnitude higher than in the Th17 cell-based study. The SKLM not only provides here key criteria for the use of such studies, but also suggests that the use of such a "checklist" requires a careful and comprehensive scientific judgement of each item. It is concluded that the Th17 cell-based study data do not represent an adequate basis for risk assessment of BPA.
Topics: Benzhydryl Compounds; Phenols; Risk Assessment; Animals; Humans; Mice; Dose-Response Relationship, Drug; Guidelines as Topic
PubMed: 38806718
DOI: 10.1007/s00204-024-03778-3 -
International Journal of Biological... Jun 2024This work involves preparing zinc manganite nanoparticles (ZnMnO NPs) using the Sol-gel method. Polymer nanocomposites of polyvinyl alcohol (PVA)/Sodium alginate...
Optical, thermal, mechanical, and antibacterial properties of polyvinyl alcohol/sodium alginate/ZnMnO nanocomposites films for various optical devices and food packaging applications.
This work involves preparing zinc manganite nanoparticles (ZnMnO NPs) using the Sol-gel method. Polymer nanocomposites of polyvinyl alcohol (PVA)/Sodium alginate (NaAlg)- ZnMnO NPs were created using the solution casting technique. The polymer nanocomposites films were made with varying weight percentages of ZnMnO nanoparticles. With the addition of nanofiller, the reduced direct and indirect energy band gap values and increased Urbach energy values were discovered in the UV-Vis data. XRD data showed a reduction in crystallinity degree with dopant. ZnMnO NPs had a strong interaction with PVA/NaAlg blend, as confirmed by FTIR. The addition of ZnMnO NPs led to improved thermal stability of the polymer nanocomposites films. Additionally, the nanocomposites films' mechanical characteristics were examined. The loading of ZnMnO nanoparticles has been associated with an increasing trend in the mechanical properties of the nanocomposites, including its toughness, Young's modulus, Tensile strength (Ts), and elongation. The antibacterial activity of the nanocomposites against fungus and bacteria was studied. Additionally, PVA/NaAlg-ZnMnO nanocomposites films had good antibacterial characteristics against environmental microorganisms such as Gram-positive (G) S. aureus and Gram-negative(G) E. coli bacteria as well as fungi C. albicans and A. niger. It was observed that the biodegradability of the nanocomposite films was lower compared to the pure PVA/NaAlg film. Compared to pure film, the water solubility was decreased upon the addition of ZnMnO NPs. After ZnMnO was added to the pure blend, the WVTR decreased. The produced polymer nanocomposites films appear to be a promising material for food packing, according to these results.
Topics: Polyvinyl Alcohol; Nanocomposites; Food Packaging; Alginates; Anti-Bacterial Agents; Tensile Strength; Mechanical Phenomena; Optical Phenomena; Staphylococcus aureus; Temperature; Zinc Compounds
PubMed: 38806084
DOI: 10.1016/j.ijbiomac.2024.132689 -
International Journal of Biological... Jun 2024The study involved preparing and applying edible nano-emulsion coatings containing hydroxypropyl methylcellulose (HPMC), beeswax (BW), and essential oils (thyme,...
The study involved preparing and applying edible nano-emulsion coatings containing hydroxypropyl methylcellulose (HPMC), beeswax (BW), and essential oils (thyme, cinnamon, clove, and peppermint) onto sweet cherries. The application was conducted at 4 °C, and the coated cherries were stored for 36 days. This research examines synthesized nano-emulsions physicochemical properties and antibacterial and antifungal activities (C, C, and C). Additionally, it evaluates the quality parameters of control and coated sweet cherry samples. The features of the three edible coatings were assessed, and the findings from the zeta sizer, zeta potential, FTIR, and SEM analyses were deemed satisfactory. It was observed that the application of nano-emulsion coating C yielded positive results in maintaining quality attributes such as total suspended solids (TSS), total solids (TS), color, weight loss, respiration rate, firmness, total phenolic contents, and sensory evaluations. Nano-emulsion coating C demonstrated efficacy as an antibacterial and antifungal agent against foodborne pathogens E. coli and A. niger, respectively. The current research results are promising and applicable in food industries. The implications suggest that composite nano-emulsion, specifically nano-emulsion edible coatings, can be extensively and effectively used to preserve the quality and shelf life of fruits and vegetables. Furthermore, the environmental waste from conventional food packaging will be minimized using edible packaging applications.
Topics: Waxes; Oils, Volatile; Hypromellose Derivatives; Anti-Bacterial Agents; Food Preservation; Food Storage; Emulsions; Cymbopogon; Edible Films; Antifungal Agents; Escherichia coli; Fruit
PubMed: 38806082
DOI: 10.1016/j.ijbiomac.2024.132532 -
International Journal of Biological... Jun 2024Gums are high-molecular-weight compounds with hydrophobic or hydrophilic characteristics, which are mainly comprised of complex carbohydrates called polysaccharides,... (Review)
Review
Gums are high-molecular-weight compounds with hydrophobic or hydrophilic characteristics, which are mainly comprised of complex carbohydrates called polysaccharides, often associated with proteins and minerals. Various innovative modification techniques are utilized, including ultrasound-assisted and microwave-assisted techniques, enzymatic alterations, electrospinning, irradiation, and amalgamation process. These methods advance the process, reducing processing times and energy consumption while maintaining the quality of the modified gums. Enzymes like xanthan lyases, xanthanase, and cellulase can selectively modify exudate gums, altering their structure to enhance their properties. This precise enzymatic approach allows for the use of exudate gums for specific applications. Exudate gums have been employed in nanotechnology applications through techniques like electrospinning. This enables the production of nanoparticles and nanofibers with improved properties, making them suitable for the drug delivery system, tissue engineering, active and intelligient food packaging. The resulting modified exudate gums exhibit improved rheological, emulsifying, gelling, and other functional properties, which expand their potential applications. This paper discusses novel applications of these modified gums in the pharmaceutical, food, and industrial sectors. The ever-evolving field presents diverse opportunities for sustainable innovation across these sectors.
Topics: Plant Gums; Drug Delivery Systems; Humans
PubMed: 38806080
DOI: 10.1016/j.ijbiomac.2024.132688 -
Anti-cancer Agents in Medicinal... May 2024Low-dose chemotherapy is a promising treatment strategy that may be improved by controlled delivery.
BACKGROUND
Low-dose chemotherapy is a promising treatment strategy that may be improved by controlled delivery.
OBJECTIVE
This study aimed to design polyethylene glycol-stabilized bilayer-decorated magnetic Cationic Liposomes (CLs) as a drug delivery system for integrated functional studies of lung cancer cell therapy and imaging.
METHOD
A novel multifunctional folic acid targeting magnetic CLs docetaxel drug-loading system (FA-CLs-Fe- DOC) was prepared and tested for its physical properties, encapsulation rate and drug release performance. The feasibility of FA-CLs-Fe-DOC ability to inhibit tumor cells and act as an MRI contrast agent was investigated in vitro, and the target recognition and therapeutic ability of FA-CLs-Fe-DOC was studied in vivo.
RESULTS
FA-CLs-Fe-DOC had a particle size of 221.54 ± 6.42 nm and a potential of 28.64 ± 3.56 mv, with superparamagnetic properties and better stability. The encapsulation rate was 95.36 ± 1.63%, and the drug loading capacity was 9.52 ± 0.22%, which possessed the drug slow-release performance and low cytotoxicity and could effectively inhibit the proliferation of lung cancer cells,promoting apoptosis of lung cancer cells. MRI showed that it had the function of tracking and localization of lung cancer cells. In vivo experiments confirmed the targeted recognition property and therapeutic function of lung cancer cells.
CONCLUSION
In this study, we successfully prepared an FA-CLs-Fe-DOC capable of specifically targeting lung cancer cells with integrated functions of efficient lung cancer cell killing and imaging localization. This targeted drug packaging technology may provide a new strategy for the design of integrated carriers for targeted cancer therapy and imaging.
PubMed: 38803174
DOI: 10.2174/0118715206294695240522075454