The Experts below are selected from a list of 246 Experts worldwide ranked by ideXlab platform
Feng Zhang - One of the best experts on this subject based on the ideXlab platform.
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understanding molecular interactions in Rafoxanide povidone amorphous solid dispersions from ultrafast magic angle spinning nmr
Molecular Pharmaceutics, 2020Co-Authors: Fa Meng, Yu Tsutsumi, Jeanpaul Amoureu, Feng ZhangAbstract:In solid dosage formulations, probing intermolecular interactions between active pharmaceutical ingredients (APIs) and polymeric excipients, which have a mechanistic impact on physical stability as well as bioavailability, remains a challenge. In recent years, solid-state NMR spectroscopy has been demonstrated to be a powerful tool to provide structural details with an atomic resolution of therapeutic organic compounds and formulation products. However, conventional 13C-detected techniques often suffer from poor resolution and low sensitivity due to the disordered structure of certain materials such as amorphous pharmaceuticals and 13C natural abundance, hindering in-depth investigations. In this study, we utilize the magic angle spinning (MAS) technique with ultrafast speeds (UF-MAS: νR = 60 and 110 kHz) and demonstrate the enabled methods with 1H detection to study the amorphous molecular complex of Rafoxanide and povidone in the solid state. The downfield shift of the RAF amide proton, resolved under UF-MAS, and its correlations with aliphatic protons of PVP, serve as strong evidence of the existence of intermolecular hydrogen bonding. Two-dimensional (2D) 1H-detected 1H{13C} and 1H-1H correlation experiments, interestingly, exhibit distinct API-polymer interactions in the spray-dried amorphous solid dispersions (ASDs), utilizing aqueous and organic cosolvents and organic solvents mixtures. The rich intermolecular interactions in the aqueously prepared ASDs presumably contribute to the physical stability, and the interactions are retained in the solution state to maintain supersaturation for an enhanced dissolution profile. This study presents the first application of UF-MAS NMR characterization of therapeutic solid dosages at a spinning frequency of 110 kHz and uncovers the molecular mechanisms of solvent-mediated pharmaceutical dispersions.
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investigating the association mechanism between Rafoxanide and povidone
Langmuir, 2018Co-Authors: Fa Meng, Zhifeng Jing, Rui Ferreira, Feng ZhangAbstract:The low aqueous solubility of most hydrophobic medications limits their oral absorption. An approach to solve this problem is to make a drug–polymer association. Herein, we investigated the association between Rafoxanide (RAF), a surface-active, poorly water-soluble drug, with a commercial hydrophilic polymer povidone. We found that the association is a function of medium composition and could only take place in polar media, such as water. The association is favored by the hydrogen-bond formation between the amide group in RAF and the carbonyl group in povidone. In addition, the association is also favored by the self-association of RAF through π–π interaction between the benzene rings in adjacent RAF molecules. Two-dimensional nuclear magnetic resonance has been applied to investigate the interactions and has confirmed our hypotheses. Geometry optimization confirmed that RAF exists primarily in the antiparallel configuration in the RAF aggregates. This study provides critical information for designing su...
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self association of Rafoxanide in aqueous media and its application in preparing amorphous solid dispersions
Molecular Pharmaceutics, 2017Co-Authors: Fa Meng, Tongzhou Liu, Elizabeth Schneide, Shehab Alzobaidi, Marco Gil, Feng ZhangAbstract:Our primary objective is to characterize the self-association of Rafoxanide in alkaline media. The second objective is to illustrate the feasibility of using Rafoxanide micellar solution as the feed solution to prepare amorphous solid dispersion via spray drying. Rafoxanide is a poorly water-soluble drug. It is a weak acid, and its poor aqueous solubility is due to its hydrophobicity. The surface-active property of Rafoxanide has not been previously reported. It was discovered that the addition of a small percentage of organic solvents is required to elevate the solubility of Rafoxanide above the critical micelle concentration to allow for the formation of micelles. Our fluorescence decay study confirms the self-association of Rafoxanide in a cosolvent consisting of 70%, v/v, NaOH solution and 30%, v/v, acetone. The position of each functional group in the micellar structures using the 1H NMR technique was identified. The critical micelle concentration of Rafoxanide in the cosolvent is determined to be 30...
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Self-Association of Rafoxanide in Aqueous Media and Its Application in Preparing Amorphous Solid Dispersions
2017Co-Authors: Fa Meng, Tongzhou Liu, Elizabeth Schneide, Shehab Alzobaidi, Marco Gil, Feng ZhangAbstract:Our primary objective is to characterize the self-association of Rafoxanide in alkaline media. The second objective is to illustrate the feasibility of using Rafoxanide micellar solution as the feed solution to prepare amorphous solid dispersion via spray drying. Rafoxanide is a poorly water-soluble drug. It is a weak acid, and its poor aqueous solubility is due to its hydrophobicity. The surface-active property of Rafoxanide has not been previously reported. It was discovered that the addition of a small percentage of organic solvents is required to elevate the solubility of Rafoxanide above the critical micelle concentration to allow for the formation of micelles. Our fluorescence decay study confirms the self-association of Rafoxanide in a cosolvent consisting of 70%, v/v, NaOH solution and 30%, v/v, acetone. The position of each functional group in the micellar structures using the 1H NMR technique was identified. The critical micelle concentration of Rafoxanide in the cosolvent is determined to be 302 μg/mL using a surface tension method. The solubility of Rafoxanide in 0.1 N NaOH solution is less than 11 μg/mL. Interestingly, the apparent solubility increased to 38,400 μg/mL in the presence of 30% acetone as the result of micelle formation. This unique solubility characteristic makes it feasible to prepare Rafoxanide amorphous solid dispersions by spray drying a predominantly aqueous (70% 0.1 N NaOH solution and 30% acetone) based feed solution. Povidone and copovidone were both used as polymeric carriers. Based on solid-state characterization, including differential scanning calorimetry, X-ray powder diffraction, and hot-stage polarized light microscopy, our results indicate that Rafoxanide solid dispersions prepared using this novel process are amorphous. Approximately 750-fold increase in the concentration of Rafoxanide in aqueous media at pH 6.8 was achieved with the amorphous solid dispersions
Nariaki Fujimoto - One of the best experts on this subject based on the ideXlab platform.
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an improved thyroid hormone reporter assay to determine the thyroid hormone like activity of amiodarone bithionol closantel and Rafoxanide
Toxicology Letters, 2012Co-Authors: Kana Matsubara, Seigo Sanoh, Shigeru Ohta, Shigeyuki Kitamura, Kazumi Sugihara, Nariaki FujimotoAbstract:Abstract A number of environmental chemicals have been reported to exhibit thyroid hormone-like activity. Since thyroid hormones play a crucial role in development, it is important to identify chemicals in the environment that are capable of endocrine disruption of thyroid hormone homeostasis. In order to detect thyroid hormone-like activity, the growth of pituitary cell lines has been commonly used as a sensitive marker, albeit with limited specificity to thyroid hormones. Reporter gene assays using the thyroid hormone responsive element (TRE) connected to the luciferase reporter gene have also been developed. Thus far however, this type of assay appears to have limited sensitivity compared to cell growth assays. In the present study, we developed a highly sensitive TRE reporter gene assay by using a pituitary cell line, MtT/E-2, and by culturing cells in a serum-free medium. Our assay was developed in order to detect T3 activity at a concentration of 10 −11 M. This assay identified thyroid hormone-like activity from the antiarrhythmic drug, amiodarone, and from three anti-parasitic drugs, bithionol, closantel and Rafoxanide, all commonly used in veterinary medicine. Thyroid hormone-like activity of these compounds was further confirmed by the induction of BCL3 gene expression in MtT/E-2, which is known to be regulated by thyroid hormones. Our improved assay was proved to be a sensitive tool for assessing thyroid hormone-like activity of environmental chemicals.
Fa Meng - One of the best experts on this subject based on the ideXlab platform.
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understanding molecular interactions in Rafoxanide povidone amorphous solid dispersions from ultrafast magic angle spinning nmr
Molecular Pharmaceutics, 2020Co-Authors: Fa Meng, Yu Tsutsumi, Jeanpaul Amoureu, Feng ZhangAbstract:In solid dosage formulations, probing intermolecular interactions between active pharmaceutical ingredients (APIs) and polymeric excipients, which have a mechanistic impact on physical stability as well as bioavailability, remains a challenge. In recent years, solid-state NMR spectroscopy has been demonstrated to be a powerful tool to provide structural details with an atomic resolution of therapeutic organic compounds and formulation products. However, conventional 13C-detected techniques often suffer from poor resolution and low sensitivity due to the disordered structure of certain materials such as amorphous pharmaceuticals and 13C natural abundance, hindering in-depth investigations. In this study, we utilize the magic angle spinning (MAS) technique with ultrafast speeds (UF-MAS: νR = 60 and 110 kHz) and demonstrate the enabled methods with 1H detection to study the amorphous molecular complex of Rafoxanide and povidone in the solid state. The downfield shift of the RAF amide proton, resolved under UF-MAS, and its correlations with aliphatic protons of PVP, serve as strong evidence of the existence of intermolecular hydrogen bonding. Two-dimensional (2D) 1H-detected 1H{13C} and 1H-1H correlation experiments, interestingly, exhibit distinct API-polymer interactions in the spray-dried amorphous solid dispersions (ASDs), utilizing aqueous and organic cosolvents and organic solvents mixtures. The rich intermolecular interactions in the aqueously prepared ASDs presumably contribute to the physical stability, and the interactions are retained in the solution state to maintain supersaturation for an enhanced dissolution profile. This study presents the first application of UF-MAS NMR characterization of therapeutic solid dosages at a spinning frequency of 110 kHz and uncovers the molecular mechanisms of solvent-mediated pharmaceutical dispersions.
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investigating the association mechanism between Rafoxanide and povidone
Langmuir, 2018Co-Authors: Fa Meng, Zhifeng Jing, Rui Ferreira, Feng ZhangAbstract:The low aqueous solubility of most hydrophobic medications limits their oral absorption. An approach to solve this problem is to make a drug–polymer association. Herein, we investigated the association between Rafoxanide (RAF), a surface-active, poorly water-soluble drug, with a commercial hydrophilic polymer povidone. We found that the association is a function of medium composition and could only take place in polar media, such as water. The association is favored by the hydrogen-bond formation between the amide group in RAF and the carbonyl group in povidone. In addition, the association is also favored by the self-association of RAF through π–π interaction between the benzene rings in adjacent RAF molecules. Two-dimensional nuclear magnetic resonance has been applied to investigate the interactions and has confirmed our hypotheses. Geometry optimization confirmed that RAF exists primarily in the antiparallel configuration in the RAF aggregates. This study provides critical information for designing su...
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self association of Rafoxanide in aqueous media and its application in preparing amorphous solid dispersions
Molecular Pharmaceutics, 2017Co-Authors: Fa Meng, Tongzhou Liu, Elizabeth Schneide, Shehab Alzobaidi, Marco Gil, Feng ZhangAbstract:Our primary objective is to characterize the self-association of Rafoxanide in alkaline media. The second objective is to illustrate the feasibility of using Rafoxanide micellar solution as the feed solution to prepare amorphous solid dispersion via spray drying. Rafoxanide is a poorly water-soluble drug. It is a weak acid, and its poor aqueous solubility is due to its hydrophobicity. The surface-active property of Rafoxanide has not been previously reported. It was discovered that the addition of a small percentage of organic solvents is required to elevate the solubility of Rafoxanide above the critical micelle concentration to allow for the formation of micelles. Our fluorescence decay study confirms the self-association of Rafoxanide in a cosolvent consisting of 70%, v/v, NaOH solution and 30%, v/v, acetone. The position of each functional group in the micellar structures using the 1H NMR technique was identified. The critical micelle concentration of Rafoxanide in the cosolvent is determined to be 30...
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Self-Association of Rafoxanide in Aqueous Media and Its Application in Preparing Amorphous Solid Dispersions
2017Co-Authors: Fa Meng, Tongzhou Liu, Elizabeth Schneide, Shehab Alzobaidi, Marco Gil, Feng ZhangAbstract:Our primary objective is to characterize the self-association of Rafoxanide in alkaline media. The second objective is to illustrate the feasibility of using Rafoxanide micellar solution as the feed solution to prepare amorphous solid dispersion via spray drying. Rafoxanide is a poorly water-soluble drug. It is a weak acid, and its poor aqueous solubility is due to its hydrophobicity. The surface-active property of Rafoxanide has not been previously reported. It was discovered that the addition of a small percentage of organic solvents is required to elevate the solubility of Rafoxanide above the critical micelle concentration to allow for the formation of micelles. Our fluorescence decay study confirms the self-association of Rafoxanide in a cosolvent consisting of 70%, v/v, NaOH solution and 30%, v/v, acetone. The position of each functional group in the micellar structures using the 1H NMR technique was identified. The critical micelle concentration of Rafoxanide in the cosolvent is determined to be 302 μg/mL using a surface tension method. The solubility of Rafoxanide in 0.1 N NaOH solution is less than 11 μg/mL. Interestingly, the apparent solubility increased to 38,400 μg/mL in the presence of 30% acetone as the result of micelle formation. This unique solubility characteristic makes it feasible to prepare Rafoxanide amorphous solid dispersions by spray drying a predominantly aqueous (70% 0.1 N NaOH solution and 30% acetone) based feed solution. Povidone and copovidone were both used as polymeric carriers. Based on solid-state characterization, including differential scanning calorimetry, X-ray powder diffraction, and hot-stage polarized light microscopy, our results indicate that Rafoxanide solid dispersions prepared using this novel process are amorphous. Approximately 750-fold increase in the concentration of Rafoxanide in aqueous media at pH 6.8 was achieved with the amorphous solid dispersions
Kana Matsubara - One of the best experts on this subject based on the ideXlab platform.
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an improved thyroid hormone reporter assay to determine the thyroid hormone like activity of amiodarone bithionol closantel and Rafoxanide
Toxicology Letters, 2012Co-Authors: Kana Matsubara, Seigo Sanoh, Shigeru Ohta, Shigeyuki Kitamura, Kazumi Sugihara, Nariaki FujimotoAbstract:Abstract A number of environmental chemicals have been reported to exhibit thyroid hormone-like activity. Since thyroid hormones play a crucial role in development, it is important to identify chemicals in the environment that are capable of endocrine disruption of thyroid hormone homeostasis. In order to detect thyroid hormone-like activity, the growth of pituitary cell lines has been commonly used as a sensitive marker, albeit with limited specificity to thyroid hormones. Reporter gene assays using the thyroid hormone responsive element (TRE) connected to the luciferase reporter gene have also been developed. Thus far however, this type of assay appears to have limited sensitivity compared to cell growth assays. In the present study, we developed a highly sensitive TRE reporter gene assay by using a pituitary cell line, MtT/E-2, and by culturing cells in a serum-free medium. Our assay was developed in order to detect T3 activity at a concentration of 10 −11 M. This assay identified thyroid hormone-like activity from the antiarrhythmic drug, amiodarone, and from three anti-parasitic drugs, bithionol, closantel and Rafoxanide, all commonly used in veterinary medicine. Thyroid hormone-like activity of these compounds was further confirmed by the induction of BCL3 gene expression in MtT/E-2, which is known to be regulated by thyroid hormones. Our improved assay was proved to be a sensitive tool for assessing thyroid hormone-like activity of environmental chemicals.
Ahmed S Saad - One of the best experts on this subject based on the ideXlab platform.
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study of thermal analysis behavior of fenbendazole and Rafoxanide
Advanced Pharmaceutical Bulletin, 2017Co-Authors: Ali K Attia, Ahmed S Saad, Manal Sami Alaraki, Ema S ElzanfalyAbstract:Purpose: Thermal analysis techniques have been applied to study the thermal behavior of fenbendazole (Fen) and Rafoxanide (Raf). Semi-empirical molecular orbital calculations were used to confirm these results. Methods: Thermogravimetric analysis, derivative thermogravimetry, differential thermal analysis and differential scanning calorimetry were used to determine the thermal behavior and purity of the drugs under investigation. Results: Thermal behavior of Fen and Raf were augmented using semi-empirical molecular orbital calculations. The purity values were found to be 99.17% and 99.60% for Fen and Raf, respectively. Conclusion: Thermal analysis techniques gave satisfactory results to obtain quality control parameters such as melting point and degree of purity at low cost, furthermore, its simplicity and sensitivity justifies its application in quality control laboratories.
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validated uplc and tlc densitometry stability indicating methods for the determination of Rafoxanide in the presence of its degradation products
Journal of Chromatographic Science, 2016Co-Authors: Ahmed S Saad, Abdallah M Hamdy, Fathy M Salama, Mohamed AbdelkawyAbstract:Two sensitive and accurate stability-indicating chromatographic methods were developed and validated for the determination of Rafoxanide (RFX). Degradation products were identified by mass spectrometry and IR spectroscopy. The first is ultra-performance liquid chromatography method where separation was performed using acetonitrile:0.005 M potassium dihydrogen orthophosphate (pH 3.5) in a ratio of 80:20 by volume as a mobile phase using a Hypersil GOLD™ C8 column 1.9 mm (50 × 2.1 mm), UV detection was adjusted at 220 nm and the flow rate was 0.6 mL min-1. The other is a thin-layer chromatography-densitometry method where separation was achieved using a mobile phase composed of chloroform:ethyl acetate:toluene:ammonia (5:4:3:0.1 by volume) on silica gel 60 F254 plates, and densitometric detection was done at 280 nm. Validation was achieved as per the ICH guidelines. The proposed methods proved to be accurate, robust, specific and suitable for application as stability-indicating methods for routine analysis of RFX in quality control laboratories.
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comparative study on the selectivity of various spectrophotometric techniques for the determination of binary mixture of fenbendazole and Rafoxanide
Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 2015Co-Authors: Ahmed S Saad, Ali K Attia, Manal Sami Alaraki, Ema S ElzanfalyAbstract:Abstract Five different spectrophotometric methods were applied for simultaneous determination of fenbendazole and Rafoxanide in their binary mixture; namely first derivative, derivative ratio, ratio difference, dual wavelength and H-point standard addition spectrophotometric methods. Different factors affecting each of the applied spectrophotometric methods were studied and the selectivity of the applied methods was compared. The applied methods were validated as per the ICH guidelines and good accuracy; specificity and precision were proven within the concentration range of 5–50 μg/mL for both drugs. Statistical analysis using one-way ANOVA proved no significant differences among the proposed methods for the determination of the two drugs. The proposed methods successfully determined both drugs in laboratory prepared and commercially available binary mixtures, and were found applicable for the routine analysis in quality control laboratories.
