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Cocaine and antidepressants rank high globally in substance consumption, emphasizing their impact on public health. The determination of these compounds and related substances in biological samples is crucial for forensic toxicology. This study focused on developing an innovative analytical method for the determination of cocaine, antidepressants, and their related metabolites in postmortem blood samples, using unmodified commercial Fe3O4 nanoparticles as a sorbent for dispersive magnetic solid-phase extraction (m-d-SPE), coupled with liquid chromatography coupled with tandem mass spectrometry (LC–MS/MS) analysis. An aliquot of 100 µL of whole blood and 5 µL of the internal standard pool were added to 30 mg of nanoparticles. The nanoparticles were separated from the sample using a neodymium magnet inserted into a 3D-printed microtube rack. The liquid was then discarded, followed by desorption with 300 µL of 1/1/1 acetonitrile/methanol/ethyl acetate. The sample was vortexed and separated, and 1.5 µL of the organic supernatant was injected into the LC–MS/MS. The method was acceptably validated and successfully applied to 263 postmortem blood samples. All samples evaluated in this study were positive for at least one substance. The most frequent analyte was benzoylecgonine, followed by cocaine and cocaethylene. The most common antidepressants encountered in the analyzed samples were citalopram and fluoxetine, followed by fluoxetine's metabolite norfluoxetine. This study describes the first report of this sorbent in postmortem blood analysis, demonstrating satisfactory results for linearity, precision, accuracy, and selectivity for all compounds. The method's applicability was confirmed, establishing it as an efficient and sustainable alternative to traditional techniques for forensic casework. [ABSTRACT FROM AUTHOR]

Alcohol is ubiquitous with unparalleled structural diversity and thus has wide applications as a native functional group in organic synthesis. It is highly prevalent among biomolecules and offers promising opportunities for the development of chemical libraries. Over the last decade, alcohol has been extensively used as an environmentally friendly chemical for numerous organic transformations. In this review, we collectively discuss the utilisation of alcohol from 2015 to 2023 in various organic transformations and their application toward intermediates of drugs, drug derivatives and natural product-like molecules. Notable features discussed are as follows: (i) sustainable approaches for C–X alkylation (X = C, N, or O) including O-phosphorylation of alcohols, (ii) newer strategies using methanol as a methylating reagent, (iii) allylation of alkenes and alkynes including allylic trifluoromethylations, (iv) alkenylation of N-heterocycles, ketones, sulfones, and ylides towards the synthesis of drug-like molecules, (v) cyclisation and annulation to pharmaceutically active molecules, and (vi) coupling of alcohols with aryl halides or triflates, aryl cyanide and olefins to access drug-like molecules. We summarise the synthesis of over 100 drugs via several approaches, where alcohol was used as one of the potential coupling partners. Additionally, a library of molecules consisting over 60 fatty acids or steroid motifs is documented for late-stage functionalisation including the challenges and opportunities for harnessing alcohols as renewable resources. [ABSTRACT FROM AUTHOR]

Betahistine (BHN) is a medication used to relieve the signs of Meniere's disease. Tinnitus, vertigo, and hearing loss are the hallmarks of Meniere's disease, a condition that affects people all over the world. In 10% of instances, a medical examination indicates a family history and genetic susceptibility. Here, a new spectrofluorimetric technique that is ultra-sensitive, inexpensive, fast, and selective was developed for the analysis of BHN in human plasma, pharmaceutical dosage form, and uniformity test. The reaction mechanism is based on the interaction of 4-chloro-7-nitrobenzofurazan with a secondary amine moiety in BHN using 0.1 M borate buffer at pH 8.8, which results in a fluorescent product detected at 535 nm (ex. at 470 nm) after heating for 15 min at 95°C. The calibration range was studied under optimum conditions, and it was linear from 0.9 to 8.0 µg/mL, with a limit of detection of 0.05 µg/mL and a limit of quantitation of 0.16 µg/mL. The investigated method was validated and bio-analytically validated using the recommendations of the International Conference of Harmonization and the US Food and Drug Administration. Additionally, the fluorimetric approach was applied to the estimation of BHN in human plasma, commercial formulations, and uniformity test with high recovery rates ranging from 96.66 to 98.00% for plasma samples. [ABSTRACT FROM AUTHOR]

• Inflammation is the cause of many diseases such as Alzheimer, heart diseases and rheumatism. • Anthemis sp. are used in traditional folk medicine for inflammatory diseases. • Inhibition of lipoxygenase enzymes is important for the prevention of inflammation. • Active molecules derived from plants are precursors for new chemical drugs. • Anthemis sp. carry compounds with drug potential. Recent studies have focused on Anthemis sp. because of their rich chemical composition and application in the treatment of diseases associated with inflammation. The purpose of this study was to determine the active chemicals responsible for the anti-inflammatory properties of Anthemis cotula, A. tomentosa, A. austriaca , and A. tinctoria var. tinctoria. Therefore, the 5-Lipoxygenase (5-LOX) was used to assess the anti-inflammatory properties of methanol extracts that were extracted from the aerial parts of the mentioned species, with an IC 50 value of 23.88 μg/mL, the methanol extract of A. tinctoria var. tinctoria demonstrated anti-inflammatory effects close to the standard (Indomethacin, IC 50 : 18.05 μg/mL). Compared to the other extracts, the methanol extract of A. tinctoria var. tinctoria demonstrated significantly greater anti-inflammatory activity. A. tinctoria var. tinctoria and A. tomentosa methanol extracts, which were the most active in comparison to other extracts, were fractionated using the bioactivity-guided fractionation method. Their anti-inflammatory properties were evaluated to determine the compounds responsible for the activity. With an IC 50 value of 3.44 μg/mL, the ethyl acetate fraction of A. tinctoria var. tinctoria (ATiEA) was found to be the most active of all the fractions. After ATiEA was further fractionated using column chromatography, it was found that ATiEA-II, one of its sub-fractions, was more effective than other sub-fractions against the 5-LOX, with an IC 50 value of 2.93 μg/mL. Furthermore, the sub-fractions' total phenol and flavonoid contents were examined to confirm their anti-inflammatory properties. The sub-fraction ATiEA-II exhibited higher total flavonoid content (743,86 μg QE/g dry weight) and total phenol content (4659.36 μg GA/g dry weight) than other sub-fractions, which was in line with its anti-inflammatory activity. GC/MS and LC-MS/MS were used to clarify the effective compounds of the sub-fraction ATiEA-II. Experiments on the anti-inflammatory properties of different Anthemis sp. have demonstrated the good anti-inflammatory potential of this species. Specifically, ATiEA-II, a sub-fraction of A. tinctoria var. tinctoria , may contain a novel anti-inflammatory drug molecule. [ABSTRACT FROM AUTHOR]

Purpose The objective of this study was to understand at what level of the Autonomous Pharmacy Framework facilities are operating, in terms of the current state of data collection and analysis in the medication-use process, and to gather insights about systems integration and automation use. Methods The Autonomous Pharmacy Advisory Board, a group of chief pharmacy officers and operational leaders, developed a self-assessment instrument based on the previously published Autonomous Pharmacy Framework, made the self-assessment instrument available via the internet, and reviewed respondents' self-reported results. The data collection period for the survey started in March of 2021 and ended in January of 2023. Results A total of 119 facility-level self-assessments were completed and analyzed. On a scale of 1 to 5, where 1 represented little or no data-driven automation with lots of manual tasks and 5 represented the utmost data-driven automation with few manual tasks, the average overall facility-level score was 2.77 (range, 1.38-4.41). Results revealed slight variance by facility bed capacity. Much more variation was found in the degrees to which individual facilities have automated core processes like inventory management, intravenous medication preparation, and financial reporting. Conclusion As a baseline, this automation-focused facility self-assessment suggests that for essentially all health-system pharmacy facilities and their larger organizations, a substantial body of work needs to be done to further develop and upgrade technology and practice in tandem, greatly expand data collection and analysis, and thereby achieve better operational, financial, and clinical outcomes. Significant advancements are needed to arrive at the highly reliable, highly automated, data-driven medication-use process involving few repetitive manual tasks envisioned in the Autonomous Pharmacy Framework. [ABSTRACT FROM AUTHOR]

This study focused on encapsulation of Rosmarinus officinalis essential oil (EO) on chitosan and gum Arabic matrix in various ratios and with varying essential oil concentrations. Additionally, UV/VIS spectroscopy was used to determine cumulative-release profiles. The insecticidal activity was tested against Tribolium castaneum and Oryzaephilus surinamensis, both pests of stored products. In terms of encapsulation efficiency (EE%) and loading capacity (LC%), capsules had EE at 45.8% and LC at 2.31%. Furthermore, many minor compounds were lost after encapsulation, until identifying only 1,8-cineole, α-terpineol, and camphor after 60 d of storage. The fumigant tests demonstrated that encapsulated EO exhibited an effective control against insect pest during storage periods, namely, 30, 45, and 60 d with 99, 66, and 46% mortality for T. castaneum and 100, 84, 82% mortality for O. surinamensis. [ABSTRACT FROM AUTHOR]

Background: Metformin, an antidiabetic drug, assists in reducing the creation of glucose inside the liver. Vildagliptin, a DPP-4 inhibitor, enhances insulin release from the pancreas and reduces the hormones that elevate blood sugar levels. The combined medications work synergistically to lower blood sugar levels. This study was designed to develop and validate a reliable method of simultaneous assessment of Metformin and Vildagliptin in bulk and pharmaceutical dosage forms. For the chromatographic separation, a Gs-Tek INNOWAX column was utilized. This column has a length of 30 m, an internal diameter of 0.25 mm, and a 1.8 µm film thickness. For the detection, a Flame Ionization Detector was utilized. The ideal conditions included an injection volume of 1 µL with a split mode of 10 to 1 ratio, a flow rate of 1 mL/minute for the nitrogen carrier gas, an injector temperature of 300 °C, a detector temperature of 250 °C, an initial oven temperature of 100 °C that was maintained for seven minutes and then programmed to climb at a rate of 10 °C per minute up to a temperature of 300 °C. Results: A gas chromatographic method that is simple, precise, accurate, robust, and reliable has been developed and implemented for the simultaneous estimation of Metformin and Vildagliptin in the tablet dosage form. The retention time for Metformin and Vildagliptin was 10.203 and 22.021 min. respectively. Validation studies were performed on the method's Linearity, detection limit (LOD), and quantitation limit (LOQ), as well as its accuracy, precision, system suitability, and robustness, using the norms established by the International Conference on Harmonization (ICH). The mean recovery value for Metformin and Vildagliptin was 100.31% (% R.S.D. = 0.6743%) and 100.33% (% R.S.D. = 0.6900%). All the results are within the acceptable range. Conclusion: Validation of the developed method revealed that all the results were within an acceptable range, and techniques can be employed to analyze these two medications in combined dosage forms. It is the first method used for simultaneous estimation of these two drugs. [ABSTRACT FROM AUTHOR]

The goal of this study was to apply the principles of analytical quality by design (AQbD) to the analytical method for determining the radiochemical purity (PQR) of the radiopharmaceutical sodium iodide 131I oral solution, utilizing thin-layer chromatography (TLC) with a radio–TLC scanner, which also enables the evaluation of product quality. For AQbD, the analytical target profile (ATP), critical quality attributes (CQA), risk management, and the method operable design region (MODR) were defined through response surface methodology to optimize the method using MINITAB® 19 software. This study encompassed the establishment of a control strategy and the validation of the method, including the assessment of selectivity, linearity, precision, robustness, detection limit, quantification limit, range, and the stability of the sample solution. Under the experimental conditions, the method parameters of the TLC scanner were experimentally demonstrated and optimized with an injection volume of 3 µL, a radioactive concentration of 10 mCi/mL, and a carrier volume of 40 µL. Statistical analysis confirmed the method's selectivity for the 131I iodide band Rf of 0.8, a radiochemical impurity IO3− Rf of 0.6, a linearity from 6.0 to 22.0 mCi/mL, and an intermediate precision with a global relative standard deviation (RSD) of 0.624%. The method also exhibited robustness, with a global RSD of 0.101%, a detection limit of 0.09 mCi/mL, and a quantification limit of 0.53 Ci/mL, meeting the prescribed range and displaying stability over time (at 0, 2, and 20 h) with a global RSD of 0.362%, resulting in consistent outcomes. The development of a method based on AQbD facilitated the creation of a design space and an operational space, with comprehensive knowledge of the method's characteristics and limitations. Additionally, throughout all operations, compliance with the acceptance criteria was verified. The method's validity was confirmed under the established conditions, making it suitable for use in the manufacturing process of sodium iodide 131I and application in nuclear medicine services. [ABSTRACT FROM AUTHOR]

The article provides information on Toripalimab-tpzi, a programmed death receptor-1 (PD-1)-blocking antibody, an antineoplastic agent. Toripalimab-tpzi is used in combination with cisplatin and gemcitabine for first-lien treatment of adults with metastatic or recurrent locally advanced nasopharyngeal carcinoma (NPC). Also mentioned are its dosage and administration, drug interactions, and advice to patients.

Background: The cardiac stress for veteran football players during match is considerable. In this specific elderly population, the kinetics of exercise-induced cardiac troponin I (cTnI) and B-Type natriuretic peptide (BNP) could potentially be related to cardiovascular risk factors (CVRF) and cardiovascular disease and are therefore be investigated for their usefulness as an complement to established screening measures. Methods: cTnI and BNP was measured in 112 veteran football players (age: 51 ± 10 years) within 30 minutes pre- and post-match. Players with elevated cTnI (cTnI-positive) and a control group (out of the 112 veteran players) with normal cTnI (cTnI-negative) underwent cardiac follow-up 4.2 ± 3.5 months post-match, comprising history, resting and stress ECG (including 30 minutes pre- and post cTnI and BNP), and echocardiography. Results: In 33 players (29%) cTnI and in 6 players BNP (5%) exceeded the upper range limit for increased risk of myocardial damage (cTnI ≥ 5 ng/l) and myocardial wall stress (BNP ≥ 100 pg/ml) post-match, respectively. No correlation was observed between Δ cTnI (pre- vs. post-match) and the number of CVRF (r = -0.06, p = 0.50). Follow-up was conducted in 62 players (31 cTnI-positive and 31 cTnI-negative players) of which 6 (10%, 3 cTnI positive and 3 cTnI negative players) had cardiac abnormalities (hypertrophic cardiomyopathy n = 2, coronary artery disease n = 2, coronary artery anomaly n = 1, hypertensive heart disease n = 1). Conclusion: Veterans' football matches elicit increases in BNP and particularly cTnI in a considerable number of players. However, these biochemical alterations do not indicate acute cardiac damage as evidenced by follow-up. Routine determination of cardiac biomarkers is unlikely to improve cardiovascular screening in veteran football players. [ABSTRACT FROM AUTHOR]

The paper examines the global scientific literature on Molecular Docking (MD). MDis a keyapproachusedinbioinformatics to identify and developnovel compounds towards drug discovery. This study uses the bibliometric method to analyze scientific data covered in the Scopus database from 2013 to 2022 using MS Excel, R Studio, andVOS Viewer software. A total of 12173 documents on Molecular Docking were retrieved and considered for the study. The paper provides an in-depth evaluation of the research output of MD. The research found that MuthuS.was a most prolific author in MD scientific research, with 98 publications that received 1481 global citations. The most productivecountries in this field areIndia (4020 publications), followedbyChina (2675 publications), Saudi Arabia (1362 publications) and Egypt (1071 publications). The hot keywords in MD research are molecular modelling, molecular docking simulation, unclassified drug and controlled study, but Molecular Docking is the burning author keyword. The finding also shows that the publications are increasing consistently from 2013 onwards. Most articles have been published in the 'Journal of Molecular Structure'. As it is an emerging and a trending topic, it has scope for further studies. This study will benefit future researchers and practitioners worldwide in understanding the research pattern on MD and identifying the other key areas related to the topic. [ABSTRACT FROM AUTHOR]

Simple Summary: All developmental stages of Stephanitis svensoni (Drake) (Hemiptera: Tingidae) are found on the underside of Japanese star anise Illicium anisatum leaves, and nymphs of the species possess glandular setae on their dorsal abdomen, from which droplets are secreted. Secretions from nymphs of the genera Stephanitis and Corythucha, belonging to the family Tingidae, are suggested to function as defensive substances against predators in a previous study. In this study, secretions from nymphs of S. svensoni were demonstrated to contain 11 compounds, including aliphatic aldehydes, aliphatic ketones, and aromatic polyketides. Antibacterial activity examination of the 10 identifiable compounds using the paper disk method showed that four compounds exhibited antibacterial activity against the Gram-positive bacterium Staphylococcus aureus, while two compounds exhibited antibacterial activity against the Gram-negative bacterium Escherichia coli. Of the two compounds that showed antibacterial activity against both bacteria, one compound showed significant antibacterial activity even at low concentrations, indicating a stronger and wider antibacterial spectrum. Nymphs of Stephanitis svensoni (Drake) (Hemiptera: Tingidae) have numerous glandular setae on their dorsal abdomens. Chemical analysis of the exudates from these setae revealed the presence of 11 compounds, including aliphatic aldehydes, aliphatic ketones, and aromatic polyketides. Among them, 3-oxododecanal, 5-hydroxy-2-heptylchromanone, and 5-hydroxy-2-undecanylchromanone were identified for the first time in the family Tingidae. Previous research has suggested that secretions from nymphs of the genus Stephanitis, belonging to the family Tingidae, function as defensive substances against predators. The exudates of S. svensoni showed antibacterial activity against the Gram-positive bacterium Staphylococcus aureus. Antibacterial tests conducted using preparations of the 10 identified compounds showed antibacterial activity in 3-oxododecanal, 2,6-dihydroxyacetophenone, and 1-(2,6-dihydroxyphenyl)dodecan-1-one. In addition, antibacterial tests against the Gram-negative bacterium Escherichia coli showed activity in 2,6-dihydroxyacetophenone and 1-(2,6-dihydroxyphenyl)dodecan-1-one. Therefore, 2,6-dihydroxyacetophenone and 1-(2,6-dihydroxyphenyl)dodecan-1-one exhibited a wide antibacterial spectrum. Particularly, 1-(2,6-dihydroxyphenyl)dodecan-1-one, which showed antibacterial activity even at low concentrations, holds promise as lead drug compound. [ABSTRACT FROM AUTHOR]

Many analytical methods are reported for simultaneous estimation of pharmaceutical dosages form. However, only a few are reproducible at an industrial scale. The proposed research aims to establish a technology transfer (TT) protocol between two laboratories (Lab-X, originator) with binary and (Lab-Y, receiver) with quaternary high-performance liquid chromatography (HPLC) system. Thus, utilizing reverse-phase HPLC (RP-HPLC), a robust, sensitive and repeatable analytical method has been developed, validated and TT between two laboratories for simultaneous estimation of Andrographolide (AG) and Paclitaxel (PTX). The method has been developed on a Phenomenex Luna C18 column (150 x 4.6, 5) sustained at 40°C and validated under the International Conference on Harmonisation (ICH) Q2 (R1) regulatory guideline and TT USP chapter 1224. The mobile phase consisted of MilliQ (pH = 3) and a combination of acetonitrile and methanol (1:1) in the ratio 50:50 with a flow rate of 0.45 mL/min, linear gradient elution in both labs. The AG and PTX were detected on the PDA detector at 224 and 227 nm wavelength with retention time of 4.5 ± 0.34 and 8.2 ± 0.02 min and limit of detection was found 0.028 ± 0.004 μg/mL, and 0.028 ± 0.0007 μg/mL, whereas limit of quantification as 0.086 ± 0.011 μg/mL and 0.088 ± 0.0014 μg/mL respectively in both labs. Throughout, this approach we have proved that proposed method is repeatable in both labs, and it can be used to quantify AG and PTX in developed pharmaceutical nano-formulations. [ABSTRACT FROM AUTHOR]

An isocratic HPLC method has been developed and validated for estimating paracetamol and diclofenac sodium simultaneously with three skeletal muscle relaxants, namely, methocarbamol, tizanidine hydrochloride and chlorzoxazone in their pure standard mixtures and in different multi-component dosage forms in a single chromatographic run. HPLC separation was achieved on a C18 Inertsil ODS-3V 5 μm column (250 × 4.6 mm) using a mobile phase mixture containing acetonitrile and 25 mM phosphate buffer (pH 7.4 adjusted with NaOH) in the proportion of (39.7:60.3, v/v) pumped at 1.2 mL/min flow rate with UV detection at 220 nm. An experimental design was used by applying Plackett–Burman design for screening the most critical predictors affecting the chromatographic separation and Box–Behnken design for optimizing the selected predictors and creating the response surface between the selected predictors and the interested responses. ICH recommendations were applied for validating the proposed method with regard to linearity, precision, accuracy, selectivity, limits of detection and quantitation, and robustness. There are many applications for the optimized method that can be applied for routine estimation of the cited drugs in laboratories of quality control and pharmaceutical industries to save money and time and to reduce material waste and effort. [ABSTRACT FROM AUTHOR]

For the purpose of identifying enantiomeric impurities in the drug substance and pharmaceutical dosage forms of the novel anti-TB medication pretomanid, an RP-high-performance liquid chromatography method was devised. To ensure the robustness of the optimized approach, analytical quality by design was used. Studies on factor screening and risk evaluation helped pinpoint the critical method parameters (CMPs); resolution (R1), analyte retention time (R2) and tailing factor (R3) are those terms. Pareto charts, half-normal plots, 3D surface plots, 2D contour plots and 3D cube plots were used to study the effects of solo and interactive CMPs on critical analytical attributes. Analysis of variance (ANOVA) was used to verify the technique parameters' confirmation of significance (P = 0.05). With a Chiral Cel OJ-3R (150 × 4.6 mm, 3 µm) and a mobile phase consisting of 20 mM of ammonium trifluoroacetate, pH = 2.5, and acetonitrile in a gradient mode, chromatographic separation was accomplished. At 30°C and 330 nm, the column's temperature and wavelength, respectively, were recorded. The procedure is stability-indicating and is LC–MS compatible. According to the International Conference on Harmonization tripartite guidelines, the method demonstrated appropriate specificity, sensitivity, linearity, accuracy, precision and robustness. The LOD and LOQ were, respectively, 0.09 and 0.3 μg/mL. With a correlation coefficient of >0.990, it was discovered that the established method for enantiomeric impurity was linear over the concentration range of 0.3–2.25μg/mL. The approach exhibits adequate accuracy (%recovery = 85–115%), robustness (%RSD = 5.0) and precision (%RSD = 5.0). The method was also shown to be stability-indicating and was shown to provide effective separation in the presence of degradation products through the use of forced degradation tests. [ABSTRACT FROM AUTHOR]

Aim: To appraise and synthesize research investigating optimizing the administration of solid oral dosage forms (SODFs) to adults with swallowing difficulties. Design: An integrative review. Methods: An electronic search was conducted on Medical Literature Analysis and Retrieval System Online (Public Medline interface), Elsevier SciVerse Scopus and Scientific Electronic Library Online (updated February 2023). Restriction regarding the publication date was not considered for the inclusion of records. Studies addressing risks, general aspects, recommendations about patient postural adjustments, swallowing techniques, swallowing aids and aspects of concealment of SODFs were included. Results: Fifty-three records published between 2002 and 2021 were included. The main administration risks were aspiration, asphyxia and solid oral dosage form-induced oral/oesophageal mucosal lesions. The most frequent general aspect reported was administering one oral dosage form at a time. The sitting position was the most patient postural adjustment mentioned. The most frequently reported solid oral dosage form swallowing technique was the lean-forward method for capsules. Solid oral dosage form swallowing aids cited: tongue and throat lubricant and solid oral dosage form coating device, swallowing cup and swallowing straw. Conclusion: The literature data on administering SODFs for adults with swallowing difficulties were appraised and synthesized. Some aspects, for example, not administering SODFs simultaneously, can make swallowing safer. Postural adjustments and solid oral dosage form swallowing aids are important to avoid administration risks. Swallowing SODFs can be easier if learned by techniques. Liquid and food are helpful as vehicles, and several of these have been listed. Implications for the Profession and/or Patient Care: By optimizing the contributing factors of administering oral pharmacotherapy, the nurse can use appropriate practices to improve patient safety. Additionally, knowing and establishing the administration aspects are reasonable steps for standardizing care for patients with swallowing oral dosage form difficulties. Impact: • This study addressed administering SODFs to adult patients with swallowing difficulties. • The administration of SODFs to adult patients with swallowing difficulties can be optimized if only one oral dosage form at a time is administrated and if patient postural adjustments, swallowing techniques and swallowing aids are used. • This investigation will impact the care of patients with swallowing difficulties. Reporting Method: The authors declare they adhered to the relevant EQUATOR guidelines and report following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 Statement. [ABSTRACT FROM AUTHOR]

A simple and robust high‐performance liquid chromatography (HPLC) method was developed for organic impurities of hydroxyzine hydrochloride in pharmaceuticals. The developed method was designed to estimate all organic impurities of hydroxyzine. The HPLC separation was achieved using C18 column (150 × 3.9 mm, 5 μm) along with a binary gradient consisting of mobile phases A (0.1%, trifluoroacetic acid in purified water) and B (0.05%, trifluoroacetic acid in acetonitrile), a flow rate of 0.7–mL/min, a column temperature of 30°C and a sample temperature of 25°C. The detection wavelength used was 230 nm for the estimation of impurity‐A, impurity‐B, and all unspecified impurities and degradation products, whereas impurity‐C was quantitated using 254 nm. The stability‐indicating property of the developed HPLC technique was assessed using stress testing conditions of hydrolysis, oxidation, thermal, photo‐light, and humidity. The validation study was performed for the limit of detection and limit of quantification, linearity, and recoveries were 0.03%, 0.05%, and 0.1132–2.9920 μg/mL (R2 > 0.999), and 84.09%–109.74%, respectively. The proposed method is highly suitable for the determination of assay, organic impurities, and degradation products of the hydroxyzine. The chemical structure of degradation product 1 (hydroxyzine N‐Oxide) and degradation product 2 (O‐Acetyl hydroxyzine) were identified with the supporting data of LC‐mass spectrometry (LC‐MS) and high‐resolution MS. [ABSTRACT FROM AUTHOR]

Background Rosacea as a skin inflammatory disease may be triggered by some types of bacteria. Azelaic acid with antibacterial property can be used for treatment of skin conditions such as Rosacea. Objective In this study, we aim to prepare and evaluate the physicochemical properties and primary stability of 15% azelaic acid gel. Methods For the gel preparation, first, an aqueous solution containing ethylenediaminetetraacetic and benzoic acids was prepared. Then, a mixture of polysorbate 80 and triglyceride was added to the solution at 50°C. Then, lecithin, propylene glycol, and carbomer 940 P was added to the mixture, and stirred. After that, the gel was prepared. Then, 15 g of dissolved azelaic acid in propylene glycol was added to the gel. Finally, the formulation was homogenized for 15 min. Results On the day of production, all the formulations had a smooth appearance and the amount of azelaic acid was about 15%. In the preliminary stability study for 3 months, the amount of azelaic acid in the formulation 5 (F5), prepared using homogenizer, was more than 99% of drug content, without any significant difference with other formulations. The released drug from F5 was 30% in the first hour and 50% after 2 hours. Conclusion All prepared formulations have acceptable pH, viscosity, and drug content. In 3 months, the highest homogeneity of azelaic acid with the lowest standard deviation was seen in the F5 formulation, indicating the importance of using homogenizer in azelaic acid gel preparation. Also, the propylene glycol 18% w/w, in addition to having a co-solvent role, can increase the release of azelaic acid from the gel. [ABSTRACT FROM AUTHOR]

Improvement to anesthesia medication safety is a useful and worthwhile area of research. Anesthesia is one of the few healthcare professions to have immediate access to compounding and label high-hazard medications at the bedside. There is a need to assess the perceptions of anesthesia medication safety and this relationship with pharmacopeia's updated recommendations for anesthesia to improve medication safety and prevent adverse drug events. Certified registered nurse anesthetist (CRNA) perceptions of medication safety climate in Florida were measured utilizing a validated Likert-scale that merged the Attitudes Questionnaire themes of teamwork, climate, safety climate, job satisfaction, stress recognition, perceptions of management, and working. The Agency for Healthcare Research and Quality Hospital Survey on Patient Safety Culture themes utilized were organizational learning, error communication, and support for patient safety. The overall email invitations delivered 5,890, 524 participants voluntarily started, and 401 completed the questionnaire resulting in a 77% completion rate. The overall response rate was 8.896% and 6.8% overall completion rate. The findings demonstrate a correlation between themes related to supportive organizational learning, stress reduction, positive changes, and creating anesthesia medication quality improvements. CRNAs' openness in adopting new pharmacopeia best practice recommendations can improve anesthesia medication safety delivery. The survey indicated clinical noteworthiness that supports the importance of additional examination of frontline providers' perceptions regarding anesthesia medication safety, buy-in, and adoption of updated pharmacopeia recommendations. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to evaluate the stability of angiotensin II in 0.9% sodium chloride for up to 5 days. Methods: We prepared angiotensin II dilutions, by aseptically diluting 2.5 mg (1 mL) in 249 mL 0.9% sodium chloride creating a solution of 10 000 ng/mL. Admixtures were stored under refrigeration (5 ± 3°C). Stability of the dilution was assessed by: preservation of clarity, consistency of pH, and retention of concentration. Solutions were sampled at times 0, 24, 48, 72, 96, 120 hours. Solutions were analyzed via High-Performance Liquid Chromatography (HPLC-UV) and Liquid Chromatography Mass Spectrometry (LC-MS/MS). Retention of concentration was set a priori at > 90% of initial concentration. Results: Clarity, color, and pH at all sample time points remained constant. Both methods of analysis confirmed similar results. When stored under refrigeration, the concentration of angiotensin II solution remained above 90% of initial concentration throughout the entire sampling period. Conclusions: Angiotensin II in 0.9% sodium chloride stored in infusion bags under refrigeration (5 ± 3°C) maintained at least 90% of their original concentrations for up to 5 days. Stability was also demonstrated based on turbidity, color, and pH assessment. [ABSTRACT FROM AUTHOR]

Artemether-lumefantrine (AL) is a highly effective and commonly used Artemisinin-based Combination Therapy (ACT) for treating uncomplicated malaria caused by Plasmodium falciparum, including drug-resistant strains. However, ineffective regulatory systems in resource-limited settings can lead to the infiltration of poor-quality and counterfeit antimalarial medicines into the pharmaceutical supply chain, causing treatment failures, prolonged illness, and disease progression. The objective of the study was to assess the quality of selected brands of fixed-dose combination (FDC) AL tablets and suspensions marketed in Kumasi, Ghana. A total of fourteen brands of FDC AL medicines, comprising eight tablets and six suspensions were purchased from various retail pharmacy outlets in Kumasi, Ghana. All samples were subjected to thorough visual inspection as a quick means of checking quality through meticulous observation of the packaging or dosage form. The quality parameters of the tablets were determined using uniformity of weight, hardness, friability, and disintegration tests. Suspensions were assessed based on pH and compared with the British Pharmacopeia (BP) standard. The samples were then analyzed for drug content (assay) using reverse-phase high-performance liquid chromatography (RP-HPLC). All the tablet samples conformed to BP specification limits for uniformity of weight (deviation of less than ± 5%), hardness (4.0–10 kg/mm2), friability (<1%), and disintegration time (<15 minutes). The active pharmaceutical ingredients' quantitative assay demonstrated that all the tablets met the BP specifications (90–110%). The results of the pH studies showed that out of the six brands of suspension investigated, five (83.3%) were compliant with the official specification for pH, while one (16.7%) failed the requirement. Unlike the tablet brands, drug content analysis of the six suspensions showed that two (33.3%) were substandard. The artemether and lumefantrine contents in these failed suspensions were variable (artemether: 81.31%–116.76%; lumefantrine: 80.35%–99.71%). The study results indicate that most of the tested products met the required quality standards, demonstrating satisfactory drug content and other quality specifications. The presence of substandard drugs underscores the necessity for robust pharmacovigilance and surveillance systems to eliminate counterfeit and substandard drugs from the Ghanaian market. [ABSTRACT FROM AUTHOR]

One of the main challenges in small molecule drug discovery is finding novel chemical compounds with desirable activity. Traditional drug development typically begins with target selection, but the correlation between targets and disease remains to be further investigated, and drugs designed based on targets may not always have the desired drug efficacy. The emergence of machine learning provides a powerful tool to overcome the challenge. Herein, a machine learning‐based strategy is developed for de novo generation of novel compounds with drug efficacy termed DTLS (Deep Transfer Learning‐based Strategy) by using dataset of disease‐direct‐related activity as input. DTLS is applied in two kinds of disease: colorectal cancer (CRC) and Alzheimer's disease (AD). In each case, novel compound is discovered and identified in in vitro and in vivo disease models. Their mechanism of actionis further explored. The experimental results reveal that DTLS can not only realize the generation and identification of novel compounds with drug efficacy but also has the advantage of identifying compounds by focusing on protein targets to facilitate the mechanism study. This work highlights the significant impact of machine learning on the design of novel compounds with drug efficacy, which provides a powerful new approach to drug discovery. [ABSTRACT FROM AUTHOR]

Despite the attractive properties of tetrafluorosulfanyl (SF4) compounds in drug discovery, medicinal research on SF4 molecules is hindered by the scarcity of suitable synthetic methodologies. Drawing inspiration from the well‐established Sonogashira cross‐coupling of terminal alkynes under Pd‐catalysis, it is envisioned that SF4‐alkynes can serve as effective coupling partners. To overcome the challenges associated with the electron‐deficient nature of SF4‐alkynes and the lability of the SF4 unit under transition‐metal catalysis, an aryl radical mediated Csp–Csp3 cross‐coupling reaction is successfully developed under Cu catalysis. This methodology facilitates the coupling of SF4‐alkynes with alkyl iodides, leading to the immediate synthesis of SF4‐attached drug‐like molecules. These findings highlight the potential impact of SF4‐containing molecules in the drug industry, paving the way for further research in this emerging field. [ABSTRACT FROM AUTHOR]

We report a versatile, Et3N-mediated thia-Michael addition–elimination reaction for producing a series of novel heteroaromatic thiol-based 2H-chromenes in good to excellent yields (59–94%). The protocol involves a one-pot reaction with mild conditions, short reaction period, simple workup procedure, and scalability. The synthesized compounds were screened with different bases and characterized by 1H NMR, 13C NMR, and HRMS. The compounds were assessed for their in vitro antibacterial activities against two pathogenic bacterial strains, E. coli and S. aureus. Among all the tested compounds, 17f and 17t exhibited the most excellent potency against both bacterial strains relative to the standard antibiotic, gentamicin, with corresponding MIC values of 12.5 (μg mL−1) and 6.25 (μg mL−1). In the SARs, the compounds 17t and 17f, having –Cl and –Br groups, respectively, showed the highest substantial antibacterial activity. The results revealed a promising lead organosulfur compound for future drug discovery. [ABSTRACT FROM AUTHOR]

Background: Pregabalin (PGB) is a medication with anticonvulsant, analgesic and anxiolytic properties, employed in the treatment of epilepsy, neuropathic pain, fibromyalgia, restless leg syndrome, opioid withdrawal syndrome and generalized anxiety disorder. Several spectrofluorimetric techniques have been documented for the determination of PGB in pharmaceutical dosage forms. However, these published methods typically involve the use of expensive and toxic organic solvents and reagents, as well as high reaction temperatures for PGB analysis. These components pose risks to aquatic life and the environment, making them less environmentally friendly and user-friendly. A recent advancement in analytical chemistry has introduced a white analytical approach, providing an economical, eco-friendly and user-friendly method for the development of analytical procedures. Objectives: Therefore, a green and sensitive spectrofluorimetric determination of PGB, guided by white analytical chemistry principles, has been conducted utilizing distilled water as an environmentally friendly solvent. Methods: The establishment of the spectrofluorimetric method involved employing the design of experiments approach to ensure a robust, precise and accurate estimation of PGB. Response surface analysis and optimization of critical procedural variables and responses were carried out using the central composite design. The validation of the developed method adhered to the guidelines outlined in ICH (International Council for Harmonization) Q2 (R1) and M10. Results: The established spectrofluorimetric method was utilized to determine the PGB content in commercially available formulations and human plasma samples spiked with PGB. The obtained results were in accordance with the labeled claim of PGB in the formulations. The recovery of PGB in the spiked human plasma samples ranged from 85 to 90% of the spiked amount. Conclusions: The greenness profiles of the published and suggested spectrofluorimetric methods for PGB estimation were evaluated and compared using the AGREE calculator, GAPI software and ESA tool. The suggested method demonstrated sensitivity, robustness, environmental friendliness and user-friendliness. [ABSTRACT FROM AUTHOR]

Background: Dosage forms (DF), which are primarily divided into solid, semisolid, liquid, and gaseous, are among the different factors that influence drug adherence. Thus, the purpose of this study was to evaluate how patients' preferences for pharmaceutical DF affected their adherence to medication in community pharmacies in Gondar town. Methods: A cross-sectional study on community pharmacies was carried out from June 25 to July 27, 2023. The statistical package for social sciences, version 26, was used for data analysis. Factors associated with patient medication discontinuation were found using both bivariate and multivariate logistic regressions. Results: According to our study, the majority of respondents (42.4%) preferred tablet DF. Most respondents (63.9%) DF preference was affected by the size of the medication, in which small-sized were most preferable (59.6%). The oral route of administration was the most preferable (71.2%). The majority of the respondents (59.9%) had a history of discontinuation of medicines. Being male (AOR=2.21, 95% CI: 1.29, 3.79), living in rural areas (AOR=1.98, 95% CI: 1.03, 3.83), types of DF (AOR=4.59, 95% CI: 1.28, 16.52), high frequency of administration (AOR=2.22, 95% CI: 1.08, 4.57), high cost of medication (AOR=3.09, 95% CI: 1.69, 5.68), getting some improvement from illness (AOR=3.29, 95% CI: 1.10, 9.87), and high number of drugs (AOR=3.29, 95% CI: 1.67, 13.85) were significantly associated with medication discontinuation. Conclusion: Our findings showed that tablet dosage forms, oral routes of administration, and once-daily taking of medicines were the most preferred by our respondents. Being male, living in rural areas, types of DF, high frequency of administration, high cost of medication, getting some improvement from illness, and high number of drugs were significantly associated with medication discontinuation. This provides an insight into what to consider when prescribing medicine to enhance patients' adherence and overall therapeutic outcomes. [ABSTRACT FROM AUTHOR]

Artificial intelligence (AI) is a discipline within the field of computer science that encompasses the development and utilization of machines capable of emulating human behavior, particularly regarding the astute examination and interpretation of data. AI operates through the utilization of specialized algorithms, and it includes techniques such as deep (DL), and machine learning (ML), and natural language processing (NLP). As a result, AI has found its application in the study of pharmaceutical chemistry and healthcare. The AI models employed encompass a spectrum of methodologies, including unsupervised clustering techniques applied to drugs or patients to discern potential drug compounds or appropriate patient cohorts. Additionally, supervised ML methodologies are utilized to enhance the efficacy of therapeutic drug monitoring. Further, AI-aided prediction of the clinical outcomes of clinical trials can improve efficiency by prioritizing therapeutic intervention that are likely to succeed, hence benefiting the patient. AI may also help create personalized treatments by locating potential intervention targets and assessing their efficacy. Hence, this review provides insights into recent advances in the application of AI and different tools used in the field of pharmaceutical medicine. [ABSTRACT FROM AUTHOR]

Rosacea, a chronic skin condition affecting millions of people in the USA, leads to significant social and professional stigmatization. Effective management strategies are crucial to alleviate symptoms and improve patients' quality of life. Encapsulated benzoyl peroxide 5% (E-BPO 5%) is a newly FDA-approved topical treatment for rosacea that shows promise in enhancing therapeutic response and minimizing skin irritation. This review aims to assess the role of recently FDA approved E-BPO 5% in the current treatment landscape for rosacea management, as it is not yet included in clinical guidelines that predominantly rely on older approved therapies. The review focuses on randomized controlled trials conducted in English-speaking adults. It evaluates the efficacy, safety, and tolerability of various US Food and Drug Administration (FDA)-approved agents used for rosacea treatment, including E-BPO cream, metronidazole gel, azelaic acid gel and foam, ivermectin cream, minocycline foam, oral doxycycline, brimonidine gel, and oxymetazoline HCl cream. Existing therapies have been effective in reducing papulopustular lesions and erythema associated with rosacea for many years. E-BPO 5% offers a promising addition to the treatment options due to its microencapsulation technology, which prolongs drug delivery time and aims to improve therapeutic response while minimizing skin irritation. Further research is necessary to determine the exact role of E-BPO 5% in the therapeutic landscape for rosacea. However, based on available evidence, E-BPO 5% shows potential as a valuable treatment option for managing inflammatory lesions of rosacea, and it may offer benefits to patients including: rapid onset of action, demonstrated efficacy by Week 2, excellent tolerability, and sustained long-term results for up to 52 weeks of treatment. [ABSTRACT FROM AUTHOR]

The flow properties of pellets or granules are crucial for further processing drug dosage forms. Optimal compression or filling of multiparticulate dosage forms into capsules is influenced by forces between discrete particles, which could be partially characterized by flow properties. Several techniques have been developed to examine flowability, including static and dynamic methods applying empirical studies and up-to-date chaos theory; however, the newest methods seem only to be powerful with the supplementation of empirical principles. Our experiments try to refine both the technique of analysis and the methods, by finding new, alternative ways. Our approach to the flowability measurements was to set up a dynamic time-dependent model that combined empirical observations and chaos theory on a geometrical basis, thus finding new characteristics regarding the flow properties of pellets and granules that could be relevant for drug developers. Our findings indicate that sphericity and particle size are the most significant factors influencing the flowability of pharmaceutical multiparticular preparations. Furthermore, this study confirms that integrating chaos theory and empirical observations in a time-dependent dynamic model provides a comprehensive understanding of particle flow behavior, pivotal for optimizing manufacturing processes. [ABSTRACT FROM AUTHOR]

Bepotastine, a second-generation antihistamine for allergic rhinitis and urticaria, is widely used in all age groups but lacks appropriate dosing guidelines for pediatric patients, leading to off-label prescriptions. We conducted this study to propose an optimal dosing regimen for pediatric patients based on population pharmacokinetic (popPK) and physiologically based pharmacokinetic (PBPK) models using data from two previous trials. A popPK model was built using NONMEM software. A one-compartment model with first-order absorption and absorption lag time described our data well, with body weight incorporated as the only covariate. A PBPK model was developed using PK-Sim software version 10, and the model well predicted the drug concentrations obtained from pediatric patients. Furthermore, the final PBPK model showed good concordance with the known properties of bepotastine. Appropriate pediatric doses for different weight and age groups were proposed based on the simulations. Discrepancies in recommended doses from the two models were likely due to the incorporation of age-dependent physiological factors in the PBPK model. In conclusion, our study is the first to suggest an optimal oral dosing regimen of bepotastine in pediatric patients using both approaches. This is expected to foster safer and more productive use of the drug. [ABSTRACT FROM AUTHOR]

Microphysiological systems (MPSs) are promising in vitro technologies for physiologically relevant predictions of the human absorption, distribution, metabolism, and excretion (ADME) properties of drug candidates. However, polydimethylsiloxane (PDMS), a common material used in MPSs, can both adsorb and absorb small molecules, thereby compromising experimental results. This study aimed to evaluate the feasibility of using the PDMS-based Emulate gut-on-chip to determine the first-pass intestinal drug clearance. In cell-free PDMS organ-chips, we assessed the loss of 17 drugs, among which testosterone was selected as a model compound for further study based on its substantial ad- and absorptions to organ chips and its extensive first-pass intestinal metabolism with well-characterized metabolites. A gut-on-chip model consisting of epithelial Caco-2 cells and primary human umbilical vein endothelial cells (HUVECs) was established. The barrier integrity of the model was tested with reference compounds and inhibition of drug efflux. Concentration–time profiles of testosterone were measured in cell-free organ chips and in gut-on-chip models. A method to deduce the metabolic clearance was provided. Our results demonstrate that metabolic clearance can be determined with PDMS-based MPSs despite substantial compound loss to the chip. Overall, this study offers a practical protocol to experimentally assess ADME properties in PDMS-based MPSs. [ABSTRACT FROM AUTHOR]

Lipophilicity, a significant physicochemical parameter of bioactive molecules, along with absorption, distribution, metabolism, excretion parameters and toxicity risk, was investigated for 32 thiazolo[3,2-b][1,2,4]triazole and imidazo[2,1-b][1,3,4]thiadiazole derivatives with anti-inflammatory potential. The experimental lipophilicity study was carried out by reversed-phase thin-layer chromatography in a binary isopropanol-water mobile phase, and the obtained results were compared with the theoretical lipophilicity parameters estimated by various computational methods. Strong correlations were found between the experimental retention factors and calculated partition coefficients. A modified Petra/Osiris/Molinspiration analysis was performed on the previously synthesized compounds, using SwissADME, Osiris and Molinspiration web tools. The predicted in silico parameters highlighted the most promising compounds as potential drug candidates. The compounds showed good gastrointestinal absorption, moderate activity according to the bioactivity score (values situated between −1.25 and −0.06), and a safe toxicity profile. The results obtained in this study will contribute to lipophilicity studies and other future studies focused on modulating new drug candidates starting from thiazolo[3,2-b][1,2,4]triazole and imidazo[2,1-b][1,3,4]thiadiazole derivatives, which are important heterocycles in medicinal chemistry. [ABSTRACT FROM AUTHOR]

In this paper, we report the synthesis of quinoxaline‐isoxazole‐piperazine conjugates. The anticancer activity was evaluated against three human cancer cell lines, including MCF‐7 (breast), HepG‐2 (liver), and HCT‐116 (colorectal). The outcomes of the tested compounds 5d, 5e, and 5f have shown more potent activity when compared to the standard drug erlotinib. In a cell survivability test (MCF‐10A), three potent compounds (5d, 5e, and 5f) were evaluated against the normal breast cell line, although neither of them displayed any significant cytotoxicity with IC50 values greater than 84 μM. Furthermore, the compounds 5d, 5e, and 5f were tested for tyrosine kinase EGFR inhibitory action using erlotinib as the reference drug and compound 5e was shown to be more potent in inhibiting the tyrosine kinase EGFR than sorafenib. In addition to this, molecular docking studies of compounds 5d, 5e, and 5f demonstrated that these compounds had more EGFR‐binding interactions. The potent compounds 5d, 5e, and 5f were subjected to in silico pharmacokinetic assessment by SWISS, ADME, and pkCSM. While the compounds 5d, 5e, and 5f followed Lipinski, Veber, Egan, and Muegge rules without any deviation. [ABSTRACT FROM AUTHOR]

Naringenin is one of the main phenolic compounds found in grapefruit (Citrus × paradisi Macfad.). This compound is known for its therapeutical properties as an antioxidant, antidiabetic, antihyperlipidemic and antineoplastic agent. In order to enable the development of drugs based on this compound, an appropriate extraction method needs to be developed. For this study, enzymatic extraction was chosen, as it is a cheap and green extraction method. Optimal extraction conditions (pH, temperature, agitation, solvent composition, sample-to-solvent ratio and enzyme-to-sample ratio) were determined through a Plackett–Burman and a Box–Behnken design, resulting in pH 6.0, 40 °C, 50 rpm, 20% EtOH, 0.2 g sample per 15 mL solvent and 1000 U/g. Once extraction conditions were determined, a single-factor experiment was performed under optimal conditions to determine extraction time, which resulted in 10 min per extraction. Finally, repeatability and intermediate precision were evaluated through naringenin quantification. Good values were obtained for both parameters (1.80% and 2.05%, respectively). Furthermore, extracts presented significant amount of naringenin (0.18 ± 0.02 mg/g). [ABSTRACT FROM AUTHOR]

The main purpose of this research was to evaluate the mass/volume percentage (%m/v) solubility of acetaminophen (ACP) in {ethanol (EtOH) (1) + propylene glycol (PG) (2) + water (3)} mixtures from 20.0 to 40.0 °C to expand the solubility database of this drug in mixed pharmaceutical solvents useful for designing high concentrated liquid products including injectable solutions. This is because ACP is an analgesic drug widely used available for oral administration as tablets or solutions. Besides, as injectable products, it is only available for perfusion in as 1 g in 100 mL (1.0%m/v). However, it is not available as 5 mL ampules for supplying doses of 500 mg. As demonstrated in this research some cosolvent mixtures allow ACP concentrations higher than 10.0%m/v, for instance the aqueous ternary mixture with 20% w/w of ethanol and 30% w/w of PG, among other possible mixtures. Flask shake method and UV–vis spectrophotometry were used for ACP solubility determinations at different temperatures. ACP solubility results are presented as Cartesian and triangular solubility profiles. ACP solubility increases with temperature arising and the cosolvent proportion in the mixtures. Maximum %m/v ACP solubility value is observed in the aqueous ethanol binary mixture of w1 = 0.80 at all temperatures being 21.18% at 25.0 °C. All the solubility values were well correlated using the Jouyban-Acree model obtaining mean percentage deviations of 3.8% (N = 330). In this way, %m/v equilibrium solubility of ACP in {EtOH + PG + water} mixtures has been studied and correlated at several temperatures as contribution to preformulation studies of injectable homogeneous liquid pharmaceutical dosage forms. [ABSTRACT FROM AUTHOR]

Cancer remains a leading cause of death worldwide, necessitating the development of innovative and more effective treatment strategies. Conventional cancer treatments often suffer from limitations such as systemic toxicity, poor pharmacokinetics, and drug resistance. Recently, there has been growing attention to utilizing natural compounds derived from various sources as possible cancer therapeutics. Natural compounds have demonstrated diverse bioactive properties, including antioxidant, anti‐inflammatory, and antitumor effects, making them attractive candidates for cancer treatment. However, their limited solubility and bioavailability present challenges for effective delivery to cancer cells. To overcome these limitations, researchers have turned to nanotechnology‐based drug delivery systems. Nanoparticles, with their small size and unique properties, can encapsulate therapeutic agents and offer benefits such as improved solubility, prolonged drug release, enhanced cellular uptake, and targeted delivery. Functionalizing nanoparticles with specific ligands further enhances their precision in recognizing and binding to cancer cells. Combining natural compounds with nanotechnology holds great promise in achieving efficient and safe cancer treatments by enhancing bioavailability, pharmacokinetics, and selectivity toward cancer cells. This review article provides an overview of the advancements in utilizing natural substances and nanotechnology‐based drug delivery systems for cancer treatment. It discusses the benefits and drawbacks of various types of nanoparticles, as well as the characteristics of natural compounds that make them appealing for cancer therapy. Additionally, current research on natural substances and nanoparticles in preclinical and clinical settings is highlighted. Finally, the challenges and future perspectives in developing natural compound‐nanoparticle‐based cancer therapies are discussed. [ABSTRACT FROM AUTHOR]

Purpose: Paclitaxel is an effective chemotherapeutic agent against a variety of cancer types. However, the clinical utility of paclitaxel is restricted by its poor solubility in water and high toxicity, resulting in low drug tolerance. These difficulties could be resolved by using suitable pharmacological carriers. Hence, it is essential to determine innovative methods of administering this effective medication to overcome paclitaxel's inherent limitations. Methods: An extensive literature search was conducted using multiple electronic databases to identify relevant studies published. Results: In this comprehensive analysis, many different paclitaxel delivery systems are covered and discussed, such as albumin-bound paclitaxel, polymeric micelles, paclitaxel-loaded liposomes, prodrugs, cyclodextrins, and peptide–taxane conjugates. Moreover, the review also covers various delivery routes of conventional paclitaxel or novel paclitaxel formulations, such as oral administration, local applications, and intraperitoneal delivery. Conclusion: In addition to albumin-bound paclitaxel, polymeric micelles appear to be the most promising formulations for innovative drug delivery systems at present. A variety of variants of polymeric micelles are currently undergoing advanced phases of clinical trials. [ABSTRACT FROM AUTHOR]

Introduction: Compounding robots are increasingly being implemented in hospital pharmacies. In our hospital, the recent acquisition of a robot (RIVATM, ARxIUM) for intravenous cancer drug compounding obliged us to replace the previously used infusion devices. The objective of the present study was to assess and qualify the new intravenous sets prior to their use in our hospital and prior to the implementation of the compounding robot. Materials and Methods: The ChemoLockTM (ICU Medical) was compared with the devices used previously for compounding (BD PhaSealTM, Becton-Dickinson) and infusion (Connect-ZTM, Codan Medical). The connection/disconnection of infusion devices to/from 50 mL infusion bags was tested with a dynamometer (Multitest-i, Mecmesin). Leakage contamination was visualized by a methylene blue assay and was quantified in simulated pump infusions with 20 mg/mL quinine sulfate (N = 36/group); after the analytical assay had been validated, quinine was detected by UV-spectrophotometry at 280 and 330 nm. Groups were compared using chi-squared or Mann–Whitney U tests. Results: The connection/disconnection test showed that although all the devices complied with the current standard, there was a statistically significant difference in the mean ± standard deviation compression force (51.5 ± 11.6 for the Connect-ZTM vs. 60.3 ± 11.7 for the ChemoLockTM; p = 0.0005). Leaks were detected in 32 (29.1%) of the 110 tests of the ChemoLockTM. The contamination rates were also significantly different: 13.9% for the BD PhaSealTM versus 75.0% for the ChemoLockTM; p < 0.0001). Discussion/conclusion: Our results showed that the new infusion device complied with current standards. However, the presence of contamination emphasizes the need for operators to use the recommended personal protective equipment. Further studies of contamination with cancer drugs are required. [ABSTRACT FROM AUTHOR]

Taxus mairei (Lemée and H.Lév.) S.Y.Hu, indigenous to the southern regions of China, is an evergreen tree belonging to the genus Taxus of the Taxaceae family. Owing to its content of various bioactive compounds, it exhibits multiple pharmacological activities and has been widely applied in clinical medicine. This article comprehensively discusses the current state of cultivation, chemical constituents, applications in the pharmaceutical field, and the challenges faced by T. mairei. The paper begins by detailing the ecological distribution of T. mairei, aiming to provide an in-depth understanding of its origin and cultivation overview. In terms of chemical composition, the article thoroughly summarizes the extracts and monomeric components of T. mairei, unveiling their pharmacological activities and elucidating the mechanisms of action based on the latest scientific research, as well as their potential as lead compounds in new drug development. The article also addresses the challenges in the T. mairei research, such as the difficulties in extracting and synthesizing active components and the need for sustainable utilization strategies. In summary, T. mairei is a rare species important for biodiversity conservation and demonstrates significant research and application potential in drug development and disease treatment. [ABSTRACT FROM AUTHOR]

E0703, a new steroidal compound optimized from estradiol, significantly increased cell proliferation and the survival rate of KM mice and beagles after ionizing radiation. In this study, we characterize its preclinical pharmacokinetics (PK) and predict its human PK using a physiologically based pharmacokinetic (PBPK) model. The preclinical PK of E0703 was studied in mice and Rhesus monkeys. Asian human clearance (CL) values for E0703 were predicted from various allometric methods. The human PK profiles of E0703 (30 mg) were predicted by the PBPK model in Gastro Plus software 9.8 (SimulationsPlus, Lancaster, CA, USA). Furthermore, tissue distribution and the human PK profiles of different administration dosages and forms were predicted. The 0.002 L/h of CL and 0.005 L of Vss in mice were calculated and optimized from observed PK data. The plasma exposure of E0703 was availably predicted by the CL using the simple allometry (SA) method. The plasma concentration–time profiles of other dosages (20 and 40 mg) and two oral administrations (30 mg) were well-fitted to the observed values. In addition, the PK profile of target organs for E0703 exhibited a higher peak concentration (Cmax) and AUC than plasma. The developed E0703-PBPK model, which is precisely applicable to multiple species, benefits from further clinical development to predict PK in humans. [ABSTRACT FROM AUTHOR]

Natural compounds such as curcumin, a polyphenolic compound derived from the rhizome of turmeric, have gathered remarkable scientific interest due to their diverse metabolic benefits including anti-obesity potential. However, curcumin faces challenges stemming from its unfavorable pharmacokinetic profile. To address this issue, synthetic curcumin derivatives aimed at enhancing the biological efficacy of curcumin have previously been developed. In silico modelling techniques have gained significant recognition in screening synthetic compounds as drug candidates. Therefore, the primary objective of this study was to assess the pharmacokinetic and pharmacodynamic characteristics of three synthetic derivatives of curcumin. This evaluation was conducted in comparison to curcumin, with a specific emphasis on examining their impact on adipogenesis, inflammation, and lipid metabolism as potential therapeutic targets of obesity mechanisms. In this study, predictive toxicity screening confirmed the safety of curcumin, with the curcumin derivatives demonstrating a safe profile based on their LD50 values. The synthetic curcumin derivative 1A8 exhibited inactivity across all selected toxicity endpoints. Furthermore, these compounds were deemed viable candidate drugs as they adhered to Lipinski's rules and exhibited favorable metabolic profiles. Molecular docking studies revealed that both curcumin and its synthetic derivatives exhibited favorable binding scores, whilst molecular dynamic simulations showed stable binding with peroxisome proliferator-activated receptor gamma (PPARγ), csyclooxygenase-2 (COX2), and fatty acid synthase (FAS) proteins. The binding free energy calculations indicated that curcumin displayed potential as a strong regulator of PPARγ (−60.2 ± 0.4 kcal/mol) and FAS (−37.9 ± 0.3 kcal/mol), whereas 1A8 demonstrated robust binding affinity with COX2 (−64.9 ± 0.2 kcal/mol). In conclusion, the results from this study suggest that the three synthetic curcumin derivatives have similar molecular interactions to curcumin with selected biological targets. However, in vitro and in vivo experimental studies are recommended to validate these findings. [ABSTRACT FROM AUTHOR]

Background Analytical tests were conducted to investigate the use of N-bromosuccinimide (NBS) as an important, safe analytical reagent for the spectrophotometric detection of therapeutically significant dihydropyridine-based calcium antagonists (DHP), namely nifedipine (NIF) and amlodipine (AML), which have been demonstrated to possess antioxidant activity in vivo and to reduce the intracellular production of reactive oxygen species (ROS). Following the reaction of DHP and NBS in acidic media, the excess NBS was evaluated for the first time by its interaction with P-aminophenol (PAP), which produced a violet-colored product that was detected at 556 nm. Objective The analytical method was performed and validated since different variables disturbing the reaction (concentration of reagent, type and concentration of the selected acid, reaction time and the diluting solvents) were carefully studied and optimized. Methods The stoichiometry of the applied reaction was determined by Job's method of continuous variation. Monitoring of these drug dosage forms' content uniformity is a first tool or evidence for their efficacy and safety after their administration. Results Beer's law was obeyed in the concentration range 1.25–11.0 µg/mL for NIF and 1.25–10.0 µg/mL for AML. The calculated limit of detection (LODs) and limit of quantification (LOQs) for NIF and AML were 0.220, 0.155 µg/mL and 0.519, 0.735 µg/mL, respectively. The precision of the applied method was satisfactory; the RSDs did not exceed 2%. Two greenness assessment tools, the Green Analytical Procedure Index (GAPI) and Analytical Greenness Metric for Sample Preparation (AGREEprep) were used for measuring the environmental friendliness of the recommended method. Conclusion The micro-determinations of content uniformity for NIF and AML in their pharmaceutical dosage forms were extremely comparable with those from official and validated procedures. Highlights A validated indirect spectrophotometric method for accurate quantification of some 1,4-dihydropyridine drugs using NBS with the aid of PAP. Monitoring of NIF and AML dosage forms' content uniformity as a first tool or evidence for their efficacy and safety after their administration. Greenness evaluation tools, GAPI and AGREEprep, for measuring the environmental friendliness of the recommended method. [ABSTRACT FROM AUTHOR]

Objective: To assess the efficacy and safety of fixed-dose combinations (FDC) of triple-drug dapagliflozin, sitagliptin, and metformin (DSM) compared with FDC of two-drug sitagliptin and metformin (SM), in Indian adult patients with type 2 diabetes (T2D). Methods: A multicentric, randomized, double-blind, active-controlled, Phase 3 study (CTRI/2021/10/037461) was conducted on 274 Indian adult patients with T2D. Patients were randomized (1:1) to receive either an FDC of triple-drug (n = 137) dapagliflozin propanediol 10 mg, sitagliptin phosphate 100 mg, and metformin hydrochloride 1000 mg extended-release (DSM) or FDC of two-drug (n = 137) sitagliptin phosphate 100 mg and metformin hydrochloride 1000 mg sustained-release (SM), for 16 weeks. The primary endpoint was a change in HbA1c, while the secondary endpoints were changes in fasting plasma glucose (FPG), postprandial glucose (PPG), body weight, and safety. Results: Both DSM and SM FDCs reduced HbA1c significantly (-1.45% and -1.00%, respectively, both p < 0.0001), however, HbA1c lowering was superior with DSM (∆ -0.45%; p = 0.0005) compared to SM, at week 16. Similarly, both DSM and SM FDCs reduced FPG and PPG significantly, however, FPG (∆ -12.4 mg/dl; p = 0.003) and PPG reduction (∆ -18.45 mg/dl; p = 0.01) were significantly superior to DSM compared to SM, respectively. No significant reduction in body weight was observed between the two arms. Both FDCs were well tolerated. Conclusion: FDC of DSM was superior to SM in reducing HbA1c, FPG, and PPG in Indian adults with T2D. Both triple and dual FDCs had optimal safety profiles. [ABSTRACT FROM AUTHOR]

Purpose In current hospital pharmacy practice, the need to compound medications ahead of patient orders often results in an increase in medication waste. The purpose of this study was to implement a strategic approach for anticipatory sterile compounding and evaluate its effect on the reduction of expired medication waste. Methods This was a pre-/post-intervention quasi-experimental study with 3 weeks of data collection for both arms and a 1-week washout period to implement process changes. A par log was placed on the medication storage refrigerator used for anticipatory compounding, with minimum and maximum levels determined by the demand-forecasting model. The primary outcome was the percentage of observations associated with waste. The secondary outcomes were the overall percentage of sterile compounding spending attributable to waste, median wasted dollars per sterile compounded product, and median dollars spent per sterile product compounded as anticipatory stock. Descriptive statistics were calculated using Minitab version 20, with the α level set to 0.05. Results A total of 4,619 observations were included in the analysis: 2,433 in the preintervention group and 2,186 in the postintervention group. Despite the median price being higher in the postintervention group than in the preintervention group, both the primary and secondary outcomes indicated that waste was reduced following the intervention. Conclusion Overall, implementation of the framework reduced sterile products waste at our institution. More research is needed to evaluate the effects of this framework at institutions of different sizes and with different patient populations. Further research on probabilistic models for sterile compounded products is also needed. [ABSTRACT FROM AUTHOR]

This study proposes the application of carboxymethyl starch derivatives as tablet coatings affording gastro-protection. Carboxymethyl starch (CMS) films were obtained by casting of aqueous filmogenic starch solutions with or without plasticizers and their structural organization was followed using Fourier transform infrared (FTIR), Thermogravimetric analysis (TGA), X-ray diffraction (XRD). Together with data from mechanical tests (tensile strength, elongation, Young's modulus) the results were used to select filmogenic formulations adapted for coatings of tablets. The behaviour of these films was evaluated in simulated gastric and intestinal fluids. The effect of plasticizers (glycerol and sorbitol) on the starch organization, on the rate of drying of the films and on the water vapor absorption was also analyzed. Various types of starch have been compared and the best results were found with high amylose starch (HAS) that was carboxymethylated in an aqueous phase to obtain carboxymethyl high amylose starch (CMHAS). The CMHAS coating solutions containing sorbitol or glycerol as plasticizers have been applied with an industrial pan coater and the final tablets exhibited a good gastro-resistance (up to 2h) in simulated gastric fluid followed by disintegration in simulated intestinal fluid (SIF). The CMHAS derivatives present a high potential as coatings for nutraceutical and pharmaceutical solid dosage forms. [Display omitted] • Homogeneous coatings were obtained using an aqueous formulation of CMHAS and sorbitol plasticizer. • CMHAS enteric coatings resisted for 2h in gastric acidity (pH 1.2) and were disrupted only at neutral pH 6.8. • Reduced solubility and high mechanical strength of CMHAS cast films are predictive for the selection of a good enteric coating formulation. • In the presence of alpha-amylase at neutral pH the coatings were totally disintegrated. • Amylose: Amylopectin ratio and gelatinization conditions are determinants for the CMHAS coating features. [ABSTRACT FROM AUTHOR]

In the current work, favipiravir (an antiviral drug) loaded pH-responsive polymeric hydrogels were developed by the free redical polymerization technique. Box-Behnken design method via Design Expert version 11 was employed to furnish the composition of all hydrogel formulations. Here, polyethylene glycol (PEG) has been utilized as a polymer, acrylic acid (AA) as a monomer, and potassium persulfate (KPS) and methylene-bisacrylamide (MBA) as initiator and cross-linker, respectively. All networks were evaluated for in-vitro drug release (%), sol-gel fraction (%), swelling studies (%), porosity (%), percentage entrapment efficiency, and chemical compatibilities. According to findings, the swelling was pH sensitive and was shown to be greatest at a pH of 6.8 (2500%). The optimum gel fraction offered was 97.8%. A sufficient porosity allows the hydrogel to load a substantial amount of favipiravir despite its hydrophobic behavior. Hydrogels exhibited maximum entrapment efficiency of favipiravir upto 98%. The in-vitro release studies of drug-formulated hydrogel revealed that the drug release from hydrogel was between 85 to 110% within 24 h. Drug-release kinetic results showed that the Korsmeyer Peppas model was followed by most of the developed formulations based on the R2 value. In conclusion, the hydrogel-based technology proved to be an excellent option for creating the sustained-release dosage form of the antiviral drug favipiravir. [ABSTRACT FROM AUTHOR]

Glioma, with its heterogeneous microenvironments and genetic subtypes, presents substantial challenges for treatment prediction and development. We integrated 3D bioprinting and multi-algorithm machine learning as a novel approach to enhance the assessment and understanding of glioma treatment responses and microenvironment characteristics. The bioprinted patient-derived glioma tissues successfully recapitulated molecular properties and drug responses of native tumors. We then developed GlioML, a machine learning workflow incorporating nine distinct algorithms and a weighted ensemble model that generated robust gene expression-based predictors, each reflecting the diverse action mechanisms of various compounds and drugs. The ensemble model superseded the performance of all individual algorithms across diverse in vitro systems, including sphere cultures, complex 3D bioprinted multicellular models, and 3D patient-derived tissues. By integrating bioprinting, the evaluative scope of the treatment expanded to T cell-related therapy and anti-angiogenesis targeted therapy. We identified promising compounds and drugs for glioma treatment and revealed distinct immunosuppressive or angiogenic myeloid-infiltrated tumor microenvironments. These insights pave the way for enhanced therapeutic development for glioma and potentially for other cancers, highlighting the broad application potential of this integrative and translational approach. [ABSTRACT FROM AUTHOR]

Unani physicians have paid great attention to the use of cosmetics since very ancient times. Around 4000 BC first archaeological evidence of cosmetics usage was found in ancient Egypt. The use of perfumes, oils, burning of aromatic incense, copper eye shadows, lamp black for eyes and dying of hairs red were in practice by ancient Egyptians. Unani literature is very rich in cosmeceutical formulations taking care of appearance and dealing with cosmetic diseases in humans. In Unani classical text like Kitab-ul-Mansoori, Al-Hawi-fil-Tib, Kamil-us-Sana, Al-Qanoon-fit-Tib, Zakheera-e-Khwarzam Shahi, the details of cosmetics are mentioned under the headings of Tazeeniyaat. This systematic review can be concluded that various cosmetics and cosmeceuticals prevailing in contemporary era may have been introduced or inspired by these physicians. There are several single drugs or compound formulations described in Unani classical text. Unani cosmetics can be a very good choice owing to their range, low cost and safety and can also be incorporated as an adjuvant in several contemporary preparation. There are several Unani cosmeceuticals are described in unani classical text like Solid Cosmeceutical (Ghaza, Ghaliya, Kajal), Semi-solid Cosmeceutical (Tila, Zimad, Ubtan) and Liquid cosmeceutical (Ghusool, Pashoya). [ABSTRACT FROM AUTHOR]

Binary mixtures of active pharmaceutical ingredients (API) are researched to improve the oral bioavailability of pharmaceutical dosage forms. The purpose of this study was to obtain mixtures of meloxicam and L-tartaric acid because tartaric acid improves intestinal absorption and meloxicam is more soluble in a weakly basic environment. The mixtures in the 0–1 molar fraction range, obtained from solvent-assisted mechanosynthesis, were investigated by differential scanning calorimetry (DSC), Fourier Transform Infrared (FTIR) spectroscopy, Fourier Transform Raman spectroscopy (FT-Raman), X-ray powder diffraction (XRD) and solubility tests. The physicochemical characteristics of the compounds obtained from DSC data reveal, for the first time, the formation of a co-crystal at meloxicam molar fraction of 0.5. FTIR spectroscopy data show the existence of hydrogen bonds between the co-crystal components meloxicam and L-tartaric acid. FT-Raman spectroscopy was used complementary with FT-IR spectroscopy to analyze the pure APIs and their mixtures, to emphasize the appearance/disappearance and the shifts of the position/intensity of vibrational bands, following the formation of hydrogen-bonded structures or van der Waals interactions, and to especially monitor the crystal lattice vibrations below 400 cm−1. The experimental results obtained by X-ray powder diffraction confirmed the formation of the co-crystal by the loss and, respectively, the apparition of peaks from the single components in the co-crystal diffractogram. The solubility tests showed that the co-crystal product has a lower aqueous solubility due to the acidic character of the other component, tartaric acid. However, when the solubility tests were performed in buffer solution of pH 7.4, the solubility of meloxicam from the co-crystal mixture was increased by 57% compared to that of pure meloxicam. In conclusion, the studied API mixtures may be considered potential biomaterials for improved drug release molecular solids. [ABSTRACT FROM AUTHOR]

An important objective of the present work is to develop and validate a novel LC-QTOF-MS/MS method to identify and quantify 5-Nitro-2-(propylthio) pyrimidine-4,6-diol genotoxic impurity at trace level (∼8.33 ppm) in ticagrelor drug substance, is an antiplatelet medicine used in the treatment of heart attacks and strokes. The potential genotoxic impurities must be controlled below acceptance limit during process of ticagrelor synthesis and release. In reversed-phase mode, the ACQUITY UPLC CSH C18 (2.1 mm x 100 mm, 1.7 μm) with ambient column temperature was used. 0.1% formic acid in Milli-Q water and methanol in the ratio of 30:70 v/v used as mobile phase A and mobile phase B with isocratic elution mode and the run time was 8.0 min. The flow rate was maintained at 0.25 mL/min, autosampler temperature was 5°C, Injection volume was 20 μL. The Retention time of 5-Nitro-2-(propylthio)pyrimidine-4,6-diol was found at 1.345 minutes. Limit of detection (LOD) and limit of quantification (LOQ) were found at 0.56 ppm and 1.67 ppm, respectively. The 5-Nitro-2-(propylthio)pyrimidine-4,6-diol was linear (R2=0.9986) over the concentration range 1.666 to 12.495 ppm. The method was accurate and precise, it was demonstrated by calculating the %mean recovery values ranging from 98.0-106.9%. [ABSTRACT FROM AUTHOR]