-
Organic Process Research & Development Apr 2024A digital design tool that can transfer material property information between unit operations to predict the product attributes in integrated purification processes has...
A digital design tool that can transfer material property information between unit operations to predict the product attributes in integrated purification processes has been developed to facilitate end-to-end integrated pharmaceutical manufacturing. This work aims to combine filtration and washing operations frequently using active pharmaceutical ingredient (API) isolation. This is achieved by coupling predicted and experimental data produced during the upstream crystallization process. To reduce impurities in the isolated cake, a mechanistic model-based workflow was used to optimize an integrated filtration and washing process model. The Carman-Kozeny filtration model has been combined with a custom washing model that incorporates diffusion and axial dispersion mechanisms. The developed model and approach were applied to two systems, namely, mefenamic acid and paracetamol, which are representative compounds, and various crystallization and wash solvents and related impurities were used. The custom washing model provides a detailed evolution of species concentration during washing, simulating the washing curve with the three stages of the wash curve: constant rate, intermediate stage, and diffusion stage. A model validation approach was used to estimate cake properties (e.g., specific cake resistance, cake volume, cake composition after washing, and washing curve). A global systems analysis was conducted by using the calibrated model to explore the design space and aid in the setup of the optimization decision variables. Qualitative optimization was performed in order to reduce the concentration of impurities in the final cake after washing. The findings of this work were translated into a final model to simulate the optimal isolation conditions.
PubMed: 38660378
DOI: 10.1021/acs.oprd.3c00480 -
Journal of Medicine and Life Dec 2023The inappropriate use of analgesics and antibiotics is a widespread issue among dentists globally, leading to the risk of over-prescription that could negatively affect...
The inappropriate use of analgesics and antibiotics is a widespread issue among dentists globally, leading to the risk of over-prescription that could negatively affect patient health and quality of life. This study aimed to assess the prescribing patterns of analgesics and antibiotics by dentists in Kirkuk City, Iraq, focusing on their attitudes, knowledge levels, and practices regarding these medications. A cross-sectional survey was conducted among 280 dentists in Kirkuk City. The dentists were contacted via their work email addresses, and they responded to a survey. Descriptive statistics, including frequency analysis, were employed to evaluate the appropriateness of analgesic and antibiotic prescriptions for different dental conditions. The first-choice analgesic for 44.6% of dentists was mefenamic acid, followed by paracetamol (31.1%). Regarding antibiotic use, 56.8% of dentists in Kirkuk City reported using antibiotics for empirical and direct therapy. Other dentists (43.2%) revealed that they did not have enough information regarding antibiotic group preference in empirical therapy. 106 of the participants (37.85%) recommended the use of broad-spectrum antibiotics in the treatment of bacterial infections. However, most (45%) were unfamiliar with the group preferences in empirical therapy. Dentists in Kirkuk City showed variations in knowledge and awareness regarding using analgesics and antibiotics. This requires further education and training on proper analgesics and antibiotic stewardship guidelines.
Topics: Humans; Anti-Bacterial Agents; Cross-Sectional Studies; Iraq; Quality of Life; Practice Patterns, Dentists'; Analgesics; Prescriptions; Dentists
PubMed: 38585523
DOI: 10.25122/jml-2023-0405 -
Therapeutic Delivery Mar 2024Amide-linked amylose-based prodrugs were developed for colon-targeted release of mefenamic acid. Activation of prodrug was studied spectrophotometrically,...
Amide-linked amylose-based prodrugs were developed for colon-targeted release of mefenamic acid. Activation of prodrug was studied spectrophotometrically, enzyme-linked immunosorbent assay appraised cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) inhibition at different concentrations of the prodrug, the behavior of prodrug under physiological conditions was monitored by scanning electron microscopy. Prodrug was poorly activated in the enzyme-free simulated gastric media and simulated intestinal media (SIM) but preincubation in pancreatin followed by treatment in aminopeptidase containing SIM led to a significant activation of prodrug. Amide-linked amylose-mefenamic acid conjugates showed a slow release in simulated gastric media and a controlled release in SIM with pancreatin playing an important role in drug release.
PubMed: 38497152
DOI: 10.4155/tde-2023-0106 -
Chemico-biological Interactions Apr 2024Drug metabolism is an essential process that chemically alters xenobiotic substrates to activate or terminate drug activity. Myeloperoxidase (MPO) is a... (Comparative Study)
Comparative Study Review
Drug metabolism is an essential process that chemically alters xenobiotic substrates to activate or terminate drug activity. Myeloperoxidase (MPO) is a neutrophil-derived haem-containing enzyme that is involved in killing invading pathogens, although consequentially, this same oxidative activity can produce metabolites that damage host tissue and play a role in various human pathologies. Cytochrome P450s (CYPs) are a superfamily of haem-containing enzymes that are significantly involved in the metabolism of drugs by functioning as monooxygenases and can be induced or inhibited, resulting in significant drug-drug interactions that lead to unanticipated adverse drug reactions. In this review, the functions of drug metabolism of MPO and CYPs are explored, along with their involvement and association for common enzymatic pathways by certain xenobiotics. MPO and CYPs metabolize numerous xenobiotics, although few reported studies have made a direct comparison between both enzymes. Additionally, we employed molecular docking to compare the active site and haem prosthetic group of MPO and CYPs, supporting their similar catalytic activities. Furthermore, we performed LCMS analysis and observed a shared hydroxylated mefenamic acid metabolite produced in both enzymatic systems. A proper understanding of the enzymology and mechanisms of action of MPO and CYPs is of significant importance when enhancing the beneficial functions of drugs in health and diminishing their damaging effects on diseases. Therefore, awareness of drugs and xenobiotic substrates involved in MPO and CYPs metabolism pathways will add to the knowledge base to foresee and prevent potential drug interactions and adverse events.
Topics: Humans; Cytochrome P-450 Enzyme System; Heme; Molecular Docking Simulation; Neutrophils; Oxidative Stress; Peroxidase; Xenobiotics
PubMed: 38458309
DOI: 10.1016/j.cbi.2024.110942 -
Chemico-biological Interactions Apr 2024The study investigates the anticancer activity of mefenamic acid against osteosarcoma, shedding light on its underlying mechanisms and therapeutic potential. Mefenamic...
The study investigates the anticancer activity of mefenamic acid against osteosarcoma, shedding light on its underlying mechanisms and therapeutic potential. Mefenamic acid exhibited robust inhibitory effects on the proliferation of MG-63, HOS, and H2OS osteosarcoma cells in a dose-dependent manner. Moreover, mefenamic acid induced cellular toxicity in MG63 cells, as evidenced by LDH leakage, reflecting its cytotoxic impact. Furthermore, mefenamic acid effectively suppressed the migration and invasion of MG-63 cells. Mechanistically, mefenamic acid induced apoptosis in MG-63 cells through mitochondrial depolarization, activation of caspase-dependent pathways, and modulation of the Bcl-2/Bax axis. Additionally, mefenamic acid promoted autophagy and inhibited the PI3K/Akt/mTOR pathway, further contributing to its antitumor effects. The molecular docking studies provide compelling evidence that mefenamic acid interacts specifically and strongly with key proteins in the PI3K/AKT/mTOR pathway, suggesting a novel mechanism by which mefenamic acid could exert anti-osteosarcoma effects. In vivo studies using a xenograft mouse model demonstrated significant inhibition of MG-63 tumor growth without adverse effects, supporting the translational potential of mefenamic acid as a safe and effective therapeutic agent against osteosarcoma. Immunohistochemistry staining corroborated the in vivo findings, highlighting mefenamic acid's ability to suppress tumor proliferation and inhibit the PI3K/AKT/mTOR pathway within the tumor microenvironment. Collectively, these results underscore the promising therapeutic implications of mefenamic acid in combating osteosarcoma, warranting further investigation for clinical translation and development.
Topics: Humans; Animals; Mice; Mefenamic Acid; Signal Transduction; Proto-Oncogene Proteins c-akt; Phosphatidylinositol 3-Kinases; Heterografts; Molecular Docking Simulation; Osteosarcoma; TOR Serine-Threonine Kinases; Cell Proliferation; Apoptosis; Cell Line, Tumor; Bone Neoplasms; Tumor Microenvironment
PubMed: 38423378
DOI: 10.1016/j.cbi.2024.110931 -
Cureus Jan 2024Perioperative hypersensitivity reactions vary from mild to potentially fatal anaphylaxis, resulting in significant morbidity and mortality. Most of the perioperative...
Perioperative hypersensitivity reactions vary from mild to potentially fatal anaphylaxis, resulting in significant morbidity and mortality. Most of the perioperative hypersensitivity and allergic reactions are attributed to antibiotics, antiseptic solutions, latex, and opioids. In the current thrust for opioid-free anesthesia, owing to its multiple advantages, paracetamol and nonsteroidal antiinflammatory agents play a significant role in multi-modal pain and inflammatory response management. Nearly nine out of ten individuals experience postoperative pain, one-third experience postoperative nausea and vomiting, and one-fourth experience fever, irrespective of surgery and type of anesthesia, often as an inflammatory response. While perioperative hypersensitivity reactions are common, a patient allergic to multiple commonly used drugs for the treatment of pain, fever, acid-peptic disorder, and nausea and vomiting is scarce. Such cases pose a great challenge in perioperative management. A 14-year-old male child with a traumatic foot drop planned for tibialis posterior tendon transfer developed an allergic reaction with mild fever following an injection of Ranitidine and Ondansetron in the preoperative area. Surgery was deferred and was investigated for allergy profile testing for commonly used drugs, which showed high IgE levels and moderate to severe hypersensitivity for diclofenac and paracetamol. The patient was operated on after one month under spinal anesthesia, avoiding ranitidine, ondansetron, diclofenac, and paracetamol. The following morning, he developed a high-grade fever (102.3° F), which did not resolve with conservative measures. Hypersensitivity and allergic reactions to NSAIDs are reported in the literature. While there are multiple drugs available as NSAIDs, cross-sensitivity or allergy to other drugs within the same group, and even chemically related groups, is also another possibility that needs to be considered while managing such patients. Mefenamic acid controlled the fever, and the child was discharged home after 48 hours of observation. However, the case posed a great perioperative management dilemma; the present report intends to highlight and discuss it.
PubMed: 38410320
DOI: 10.7759/cureus.53015 -
International Journal of Biological... Mar 2024The crosslinking of the polymer matrix with compatible macromolecules results in a three-dimensional network structure that offers an enhancement in the controlled...
The crosslinking of the polymer matrix with compatible macromolecules results in a three-dimensional network structure that offers an enhancement in the controlled release properties of the material. In this sense, this work aimed to improve the release profile of mefenamic acid (MAC) through crosslinking strategies. κ-Carrageenan/sericin crosslinked blend was obtained by covalent and thermal crosslinking and the different formulations were characterized. The gastroresistant potential and release profile were evaluated in the dissolution assay. The effect and characterization of the particles were investigated. Multiple units presented high entrapment efficiency (94.11-104.25), high drug loading (36.50-47.50 %) and adequate particle size (1.34-1.57 mm) with rough surface and visually spherical shape. The Weibull model showed that drug release occurred by relaxation, erosion and Fickian diffusion. Material stability and absence of MAC -polymer interactions were demonstrated by FTIR and thermogravimetric analysis. DSC showed a stable character of MAC in the drug-loaded beads. Moreover, the application studies of κ-Car/Ser/carboxymethylcellulose in the in vitro intestine mode showed that the crosslinked blend increased cell viability (>85 %), while free MAC exhibited a cytotoxic effect. Finally, the crosslinked k-Car/Ser blend MAC -loaded showed promising properties of a sustained release form of anti-inflammatory drug.
Topics: Sericins; Mefenamic Acid; Polymers; Carrageenan; Drug Liberation; Delayed-Action Preparations
PubMed: 38296146
DOI: 10.1016/j.ijbiomac.2024.129823 -
AAPS PharmSciTech Jan 2024Alzheimer's disease (AD) is a very common disorder that affects the elderly. There are relatively few medications that can be used orally or as a suspension to treat AD....
Mefenamic Acid Loaded and TPGS Stabilized Mucoadhesive Nanoemulsion for the Treatment of Alzheimer's Disease: Development, Optimization, and Brain-Targeted Delivery via Olfactory Pathway.
Alzheimer's disease (AD) is a very common disorder that affects the elderly. There are relatively few medications that can be used orally or as a suspension to treat AD. A mucoadhesive (o/w) nano emulsion of mefenamic acid was made by adding Carbopol 940P to the optimised drug nanoemulsion using distilled water as the aqueous phase (6%); Solutol HS: tween 20 (3.6%) as the surfactant and co-surfactant; and clove oil: TPGS (0.4%) as the oil phase and mefenamic acid as the drug (2.8 mg/ml). The mucoadhesive nanoemulsion (S4) had a particle size of 91.20 nm, polydispersity index of 0.270, and surface charge of - 12.4 mV. Significantly higher (p < 0.001) drug release (89.37%) was observed for mucoadhesive drug formulation in comparison to mucoadhesive drug suspension (25.64%) at 8 h. The ex vivo nasal permeation of 83.03% in simulated nasal fluid and 85.71% in artificial cerebrospinal fluid was observed. The percent inhibition and inhibitory concentration (IC) of mucoadhesive drug nanoemulsion were found to be 91.57 ± 2.69 and 6.76 respectively. Higher cell viability on glioblastoma cells (85-80%) was researched for mucoadhesive nanoemulsion as compared to drug suspension (80-70%). Significantly higher (p < 0.001) drug absorption and Cmax (491.94 ± 24.13 ng/ml) of mucoadhesive drug nanoemulsion were observed than mucoadhesive drug suspension (107.46 ± 11.46 ng/ml) at 8 h. The stability studies confirmed that the formulation was stable at 40°C ± 2°C and 75 ± 5% RH. The authors concluded that the mucoadhesive mefenamic acid-loaded nanoemulsion may be an effective technique for treating Alzheimer's disease by intranasal route.
Topics: Humans; Aged; Mefenamic Acid; Olfactory Pathways; Alzheimer Disease; Brain; Surface-Active Agents; Vitamin E
PubMed: 38200387
DOI: 10.1208/s12249-023-02727-0 -
Analytica Chimica Acta Jan 2024Although NSAIDs possess notable therapeutic and pharmaceutical qualities, it's essential to acknowledge that excessive doses can result in toxicity within the human...
A novel sorbent based on electrospun for electrically-assisted solid phase microextraction of six non-steroid anti-inflammatory drugs, followed by quantitation with HPLC-UV in human plasma samples.
BACKGROUND
Although NSAIDs possess notable therapeutic and pharmaceutical qualities, it's essential to acknowledge that excessive doses can result in toxicity within the human body. Moreover, the importance lies in identifying and measuring their trace amounts. Due to their existence within intricate matrices, the creation of novel electrospun nanofibers as sorbents for electrically-assisted solidphase microextraction (EA-SPME) becomes vital. This innovation caters to the requirement for the effective pre-treatment of NSAID samples, providing a strategic approach to managing the complexities associated with trace quantities found in various matrices.
RESULTS
First, polyvinylalcohol/casein/tannic acid/polyaniline/titanium dioxide nanoparticles (PVA/CAS/TA/PANI/TiO NPs) electrospun nanofibers were prepared for EA-SPME on pewter rode and then, trace amounts of six NSAIDs (Acetaminophen, Caffeine, Naproxen, Celecoxib, Ibuprofen and mefenamic acid) were adsorbed chemically on these nanofibers. In the next step, the desorption of six NSAIDs was electrochemically done from prepared electrospun nanofibers on a pewter rod which was as working electrode at three electrodes system. Finally, these drugs were quantified from different human plasma samples with HPLC-UV. The synthesis of electrospun nanofibers was confirmed through a series of analytical techniques including field emission-scanning electron microscopy (FE-SEM), energy-dispersive X-ray spectroscopy with elemental mapping analysis (EDX-Mapping), X-ray diffraction (XRD), and Fourier transform-infrared (FT-IR). The optimal percentage of additive compounds to PVA/CAS for electrospinning, as well as the factors influencing adsorption and desorption processes, were determined through both of Design Expert software and MATLAB programming language.
SIGNIFICANCE
Under optimum conditions, the wide linear range was 27-8000 ng mL with R≥ 0.9897, low detection limits were ranged from 8 to 27.3 ng mL based on S/N = 3 and significant enrichment factors were acquired. The intra-day and inter-day RSDs% were obtained within the 4.51% - 5.68% and 4.28%-5.45%, respectively. Finally, The effectiveness of the EA-SPME-HPLC-UV method was assessed for determining NSAIDs in plasma samples, demonstrating good recoveries ranging from 90.2% to 105.2%.
Topics: Humans; Solid Phase Microextraction; Chromatography, High Pressure Liquid; Spectroscopy, Fourier Transform Infrared; Anti-Inflammatory Agents, Non-Steroidal
PubMed: 38182332
DOI: 10.1016/j.aca.2023.341839