The Experts below are selected from a list of 30 Experts worldwide ranked by ideXlab platform
David G. Meyers - One of the best experts on this subject based on the ideXlab platform.
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So Much Writing, So Little Science: A Review of 37 Years of Literature on Edetate Sodium Chelation Therapy
The Annals of pharmacotherapy, 1993Co-Authors: Michael T. Grier, David G. MeyersAbstract:OBJECTIVE:To determine the safety and efficacy of Edetate Sodium (ethylenediamine tetraacetic acid; EDTA) chelation therapy for atherosclerosis.METHODS:Literature search using MEDLINE, encompassing 1966 through May 1993. Further references were obtained from articles and books, and from citations obtained from the American Academy of Medical Preventics.RESULTS:16 case reports or case series, 2 longitudinal studies, and 3 clinical trials were reviewed, along with testimonials cited in 19 books.CONCLUSIONS:Little valid scientific evidence is available. Although the postulated mechanisms of action for EDTA are biologically plausible and EDTA appears to be safe, it has not been proven effective. Indeed, the best evidence shows it to be ineffective. Therefore, EDTA chelation therapy should not be used in clinical practice to treat atherosclerosis.
Michael T. Grier - One of the best experts on this subject based on the ideXlab platform.
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So Much Writing, So Little Science: A Review of 37 Years of Literature on Edetate Sodium Chelation Therapy
The Annals of pharmacotherapy, 1993Co-Authors: Michael T. Grier, David G. MeyersAbstract:OBJECTIVE:To determine the safety and efficacy of Edetate Sodium (ethylenediamine tetraacetic acid; EDTA) chelation therapy for atherosclerosis.METHODS:Literature search using MEDLINE, encompassing 1966 through May 1993. Further references were obtained from articles and books, and from citations obtained from the American Academy of Medical Preventics.RESULTS:16 case reports or case series, 2 longitudinal studies, and 3 clinical trials were reviewed, along with testimonials cited in 19 books.CONCLUSIONS:Little valid scientific evidence is available. Although the postulated mechanisms of action for EDTA are biologically plausible and EDTA appears to be safe, it has not been proven effective. Indeed, the best evidence shows it to be ineffective. Therefore, EDTA chelation therapy should not be used in clinical practice to treat atherosclerosis.
Henderik W. Frijlink - One of the best experts on this subject based on the ideXlab platform.
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Prefilled Cyclic Olefin Sterilized Syringes of Norepinephrine Injection Solution Do Not Need to Be Stabilized by Antioxidants
AAPS PharmSciTech, 2020Co-Authors: Karin H. M. Larmené- Beld, Rommert Wijnsma, Katja Taxis, Stefan Berkel, Henderik W. FrijlinkAbstract:Norepinephrine is a potent α-sympathomimetic drug which plays an important role in the acute treatment of hypotension and shock. Commercially available norepinephrine solutions contain Sodium metabisulfite (Na2S2O5) as an antioxidant. However, prefilled cyclic olefin polymer syringes are not compatible with Sodium metabisulfite. The aim of this study was to develop a new formulation of 0.1-mg/mL norepinephrine solution without Sodium metabisulfite which is chemically stable and sterile and can be stored in prefilled polymer syringes. Formulation studies were performed with 0.1-mg/mL norepinephrine solution with 0, 0.05, or 0.1% ascorbic acid added as antioxidant. The syringes were filled under nitrogen gassing, stored at 20 ± 5°C, and protected from daylight. Based on the formulation test results, the final formulation was defined and stability testing at 20 ± 5°C was performed measuring norepinephrine concentration, pH, clarity, color of the solution, subvisible particles, and sterility at time intervals up to 12 months. The norepinephrine concentrations at t = 22 weeks were 100.4%, 95.4%, and 92.2% for the formulations with no ascorbic acid and with 0.05% and 0.10% ascorbic acid, respectively. Three batches for the stability study were produced containing norepinephrine, Sodium Edetate, Sodium chloride, and water for injections filled under nitrogen gassing and stored at 20 ± 5°C. Norepinephrine concentrations were respectively 98.8%, 98.6%, and 99.3% for batches 1, 2, and 3 at t = 12 months. It can be concluded that norepinephrine (0.1 mg/mL) solution without metabisulfite is stable for at least 12 months at room temperature when protected from daylight.
Rommert Wijnsma - One of the best experts on this subject based on the ideXlab platform.
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Prefilled Cyclic Olefin Sterilized Syringes of Norepinephrine Injection Solution Do Not Need to Be Stabilized by Antioxidants
AAPS PharmSciTech, 2020Co-Authors: Karin H. M. Larmené- Beld, Rommert Wijnsma, Katja Taxis, Stefan Berkel, Henderik W. FrijlinkAbstract:Norepinephrine is a potent α-sympathomimetic drug which plays an important role in the acute treatment of hypotension and shock. Commercially available norepinephrine solutions contain Sodium metabisulfite (Na2S2O5) as an antioxidant. However, prefilled cyclic olefin polymer syringes are not compatible with Sodium metabisulfite. The aim of this study was to develop a new formulation of 0.1-mg/mL norepinephrine solution without Sodium metabisulfite which is chemically stable and sterile and can be stored in prefilled polymer syringes. Formulation studies were performed with 0.1-mg/mL norepinephrine solution with 0, 0.05, or 0.1% ascorbic acid added as antioxidant. The syringes were filled under nitrogen gassing, stored at 20 ± 5°C, and protected from daylight. Based on the formulation test results, the final formulation was defined and stability testing at 20 ± 5°C was performed measuring norepinephrine concentration, pH, clarity, color of the solution, subvisible particles, and sterility at time intervals up to 12 months. The norepinephrine concentrations at t = 22 weeks were 100.4%, 95.4%, and 92.2% for the formulations with no ascorbic acid and with 0.05% and 0.10% ascorbic acid, respectively. Three batches for the stability study were produced containing norepinephrine, Sodium Edetate, Sodium chloride, and water for injections filled under nitrogen gassing and stored at 20 ± 5°C. Norepinephrine concentrations were respectively 98.8%, 98.6%, and 99.3% for batches 1, 2, and 3 at t = 12 months. It can be concluded that norepinephrine (0.1 mg/mL) solution without metabisulfite is stable for at least 12 months at room temperature when protected from daylight.
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3PC-043 New formulation of norepinephrine solution in prefilled cyclic olefin sterilised syringes
Section 3: Production and Compounding, 2019Co-Authors: K Beld, S Van Berkel, Rommert Wijnsma, Katja Taxis, E FrijlinkAbstract:Background Norepinephrine is a potent α-sympathomimetic drug which plays an important role in the acute treatment of hypotension and shock in an intensive care unit. Commercially available norepinephrine solutions contain Sodium metabisulfite (Na 2 S 2 O 5 ) as an antioxidant. However, the cyclic olefin polymer syringe used in our hospital is not compatible with Sodium metabisulfite due to brown colourisation of the syringe during sterilisation. Purpose To develop a new formulation of 0.1 mg/ml norepinephrine solution without Sodium metabisulfite which is chemically stable and sterile. Material and methods Pre-formulation tests were performed with 0.1 mg/ml norepinephrine solution with 0, 0.05% and 0.1% ascorbic acid added as an antioxidant. Other excipients were 0.1 mg/ml Edetate Sodium, 8 mg/ml Sodium chloride and water for injections. The syringes were filled under nitrogen gassing, stored at room temperature and protected from daylight. Concentration of norepinephrine was measured at day 0, 8, 21 and 51, and 3 and 5 months with an UHPLC system with diode array detection. Based on the pre-formulation test results, the final formulation was defined and stability testing was performed measuring concentration of norepinephrine, pH, clarity, colour of solution, subvisible particles and sterility at time intervals according to ICH guidelines. Results The norepinephrine concentration in the pre-formulation tests were 98.4%, 96.4% and 96.4% at t=5 months for, respectively, no ascorbic acid added, and 0.10% and 0.05% ascorbic acid added. Validation batches were produced with norepinephrine, Edetate Sodium, Sodium chloride and water for injections filled under nitrogen gassing. Preliminary results show a concentration of 108.8% and 109.0% norepinephrine (10% more norepinephrine was added due to possible degradation during sterilisation based on historical data) at t=3 months. Conclusion Norepinephrine (0.1 mg/ml) solution without Sodium metabisulfite in a sterilised syringe stored at room temperature protected from daylight, is stable for at least 3 months. Reference and/or acknowledgements Larmene-Beld K, Kuiper A, van Berkel S, et al . A science- and risk-based strategy to qualify sterilised prefilled syringes as primary packaging material in a hospital pharmacy . Abstract submitted for 24th EAHP Congress 2019. No conflict of interest.
Katja Taxis - One of the best experts on this subject based on the ideXlab platform.
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Prefilled Cyclic Olefin Sterilized Syringes of Norepinephrine Injection Solution Do Not Need to Be Stabilized by Antioxidants
AAPS PharmSciTech, 2020Co-Authors: Karin H. M. Larmené- Beld, Rommert Wijnsma, Katja Taxis, Stefan Berkel, Henderik W. FrijlinkAbstract:Norepinephrine is a potent α-sympathomimetic drug which plays an important role in the acute treatment of hypotension and shock. Commercially available norepinephrine solutions contain Sodium metabisulfite (Na2S2O5) as an antioxidant. However, prefilled cyclic olefin polymer syringes are not compatible with Sodium metabisulfite. The aim of this study was to develop a new formulation of 0.1-mg/mL norepinephrine solution without Sodium metabisulfite which is chemically stable and sterile and can be stored in prefilled polymer syringes. Formulation studies were performed with 0.1-mg/mL norepinephrine solution with 0, 0.05, or 0.1% ascorbic acid added as antioxidant. The syringes were filled under nitrogen gassing, stored at 20 ± 5°C, and protected from daylight. Based on the formulation test results, the final formulation was defined and stability testing at 20 ± 5°C was performed measuring norepinephrine concentration, pH, clarity, color of the solution, subvisible particles, and sterility at time intervals up to 12 months. The norepinephrine concentrations at t = 22 weeks were 100.4%, 95.4%, and 92.2% for the formulations with no ascorbic acid and with 0.05% and 0.10% ascorbic acid, respectively. Three batches for the stability study were produced containing norepinephrine, Sodium Edetate, Sodium chloride, and water for injections filled under nitrogen gassing and stored at 20 ± 5°C. Norepinephrine concentrations were respectively 98.8%, 98.6%, and 99.3% for batches 1, 2, and 3 at t = 12 months. It can be concluded that norepinephrine (0.1 mg/mL) solution without metabisulfite is stable for at least 12 months at room temperature when protected from daylight.
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3PC-043 New formulation of norepinephrine solution in prefilled cyclic olefin sterilised syringes
Section 3: Production and Compounding, 2019Co-Authors: K Beld, S Van Berkel, Rommert Wijnsma, Katja Taxis, E FrijlinkAbstract:Background Norepinephrine is a potent α-sympathomimetic drug which plays an important role in the acute treatment of hypotension and shock in an intensive care unit. Commercially available norepinephrine solutions contain Sodium metabisulfite (Na 2 S 2 O 5 ) as an antioxidant. However, the cyclic olefin polymer syringe used in our hospital is not compatible with Sodium metabisulfite due to brown colourisation of the syringe during sterilisation. Purpose To develop a new formulation of 0.1 mg/ml norepinephrine solution without Sodium metabisulfite which is chemically stable and sterile. Material and methods Pre-formulation tests were performed with 0.1 mg/ml norepinephrine solution with 0, 0.05% and 0.1% ascorbic acid added as an antioxidant. Other excipients were 0.1 mg/ml Edetate Sodium, 8 mg/ml Sodium chloride and water for injections. The syringes were filled under nitrogen gassing, stored at room temperature and protected from daylight. Concentration of norepinephrine was measured at day 0, 8, 21 and 51, and 3 and 5 months with an UHPLC system with diode array detection. Based on the pre-formulation test results, the final formulation was defined and stability testing was performed measuring concentration of norepinephrine, pH, clarity, colour of solution, subvisible particles and sterility at time intervals according to ICH guidelines. Results The norepinephrine concentration in the pre-formulation tests were 98.4%, 96.4% and 96.4% at t=5 months for, respectively, no ascorbic acid added, and 0.10% and 0.05% ascorbic acid added. Validation batches were produced with norepinephrine, Edetate Sodium, Sodium chloride and water for injections filled under nitrogen gassing. Preliminary results show a concentration of 108.8% and 109.0% norepinephrine (10% more norepinephrine was added due to possible degradation during sterilisation based on historical data) at t=3 months. Conclusion Norepinephrine (0.1 mg/ml) solution without Sodium metabisulfite in a sterilised syringe stored at room temperature protected from daylight, is stable for at least 3 months. Reference and/or acknowledgements Larmene-Beld K, Kuiper A, van Berkel S, et al . A science- and risk-based strategy to qualify sterilised prefilled syringes as primary packaging material in a hospital pharmacy . Abstract submitted for 24th EAHP Congress 2019. No conflict of interest.
