The Experts below are selected from a list of 306 Experts worldwide ranked by ideXlab platform
Abbas Hemati Azandaryani - One of the best experts on this subject based on the ideXlab platform.
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preparation of solid lipid nanoparticles as drug carriers for Levothyroxine Sodium with in vitro drug delivery kinetic characterization
Molecular Biology Reports, 2014Co-Authors: E Rostami, Soheila Kashanian, Abbas Hemati AzandaryaniAbstract:The aim of this work was to produce and characterize solid lipid nanoparticles (SLN) containing Levothyroxine Sodium for oral administration, and to evaluate the kinetic release of these colloidal carriers. SLNs were prepared by microemulsion method. The particle size and zeta potential of Levothyroxine Sodium-loaded SLNs were determined to be around 153 nm,−43 mV (negatively charged), respectively by photon correlation spectroscopy. The Levothyroxine entrapment efficiency was over 98 %. Shape and surface morphology were determined by TEM and SEM. They revealed fairly spherical shape of nanoparticles.SLN formulation was stable over a period of 6 months. There were no significant changes in particle size, zeta potential and polydispersity index and entrapment efficiency, indicating that the developed SLNs were fairly stable.
Brent Sinclair - One of the best experts on this subject based on the ideXlab platform.
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Gluten and Aluminum Content in Synthroid® (Levothyroxine Sodium Tablets).
Advances in Therapy, 2017Co-Authors: Ramon Espaillat, Michael F. Jarvis, Cory Torkelson, Brent SinclairAbstract:Inquiries from healthcare providers and patients about the gluten and aluminum content of Synthroid® (Levothyroxine Sodium tablets) have increased. The objective of this study was to measure and evaluate the gluten content of the raw materials used in the manufacturing of Synthroid. Additionally, this study determined the aluminum content in different strengths of Synthroid tablets by estimating the amount of aluminum in the raw materials used in the manufacturing of Synthroid. Gluten levels of three lots of the active pharmaceutical ingredient (API) and one lot of each excipient from different vendors were examined. The ingredients in all current Synthroid formulations (strengths) were evaluated for their quantity of aluminum. Gluten concentrations were below the lowest limit of detection (
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gluten and aluminum content in synthroid Levothyroxine Sodium tablets
Advances in Therapy, 2017Co-Authors: Ramon Espaillat, Michael F. Jarvis, Cory Torkelson, Brent SinclairAbstract:Inquiries from healthcare providers and patients about the gluten and aluminum content of Synthroid® (Levothyroxine Sodium tablets) have increased. The objective of this study was to measure and evaluate the gluten content of the raw materials used in the manufacturing of Synthroid. Additionally, this study determined the aluminum content in different strengths of Synthroid tablets by estimating the amount of aluminum in the raw materials used in the manufacturing of Synthroid. Gluten levels of three lots of the active pharmaceutical ingredient (API) and one lot of each excipient from different vendors were examined. The ingredients in all current Synthroid formulations (strengths) were evaluated for their quantity of aluminum. Gluten concentrations were below the lowest limit of detection (<3.0 ppm) for all tested lots of the API and excipients of Synthroid tablets. Aluminum content varied across tablet strengths (range 19–137 µg/tablet). Gluten levels of the API and excipients were found to be below the lowest level of detection and are considered gluten-free based on the US Food and Drug Administration (FDA) definition for food products. Across the various tablet strengths of Synthroid, the maximum aluminum levels were well below the FDA-determined minimal risk level for chronic oral aluminum exposure (1 mg/kg/day). These data demonstrate that Synthroid tablets are not a source for dietary gluten and are a minimal source of aluminum. AbbVie Inc.
Karl Wegscheider - One of the best experts on this subject based on the ideXlab platform.
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Assessment of Levothyroxine Sodium Bioavailability
Clinical Pharmacokinetics, 2004Co-Authors: Ingeborg Walter-sack, Christof Clanget, Reinhard Ding, Christoph Goeggelmann, Vera Hinke, Matthias Lang, Johannes Pfeilschifter, Yorki Tayrouz, Karl WegscheiderAbstract:Background Assessment of dosage form performance in delivering endogenous compounds, such as hormones, in vivo requires a specific approach. Objectives Assessment of relative bioavailability of Levothyroxine Sodium (L-T4) from eight solid preparations, compared with a liquid formulation, by using pharmacological doses, and critical evaluation of trial methodology based on the pooled analysis of individual data. Design Eight open-label, randomised, single-dose, crossover phase I studies using eight solid L-T4 dosage forms (25, 50, 75, 100, 125, 150, 175, 200μg per tablet; administered total doses 600, 625 or 700μg) and a liquid formulation; assessment of relative bioavailability by 90% confidence intervals for the relative area under the concentration-time curve (AUC) of total thyroxine (TT4), i.e. protein-bound plus free thyroxine, calculated by using the recommended log AUC four-way analysis of variance models for crossover designs. For the pooled analysis, general linear models were applied to assess the validity of model assumptions, to identify potential sources of effect modification, to discuss alternative modelling approaches with respect to endogenous hormone secretion and to give recommendations for future designs and sample sizes. Participants One hundred and sixty-nine healthy males; 29 of these individuals participating in two studies. Interventions Single oral doses of L-T4 tablets and the liquid formulation administered after fasting, separated by at least 6 weeks; a total of 396 drug exposures. Main outcome measures TT4 AUC from 0 to 48 hours and peak plasma concentration with and without baseline correction. Results Each study demonstrated equivalence of the tablets to the drinking solution, independent of the chosen analysis model. Sequence effects that could devalidate the chosen crossover approach were not found. Period effects with changing directions that could best be explained by seasonal variation were detected. While the pre-specified method of baseline correction of simply subtracting individual time-zero TT4 values was disadvantageous, the analysis of total AUC could be improved considerably by covariate adjustment for baseline TT4. With this approach, sample sizes could have been substantially reduced or, alternatively, the recommended equivalence ranges could be reduced to ±6%. Conclusion: Using a single pharmacological dose of L-T4 in two-period crossover designs is a safe and reliable procedure to assess L-T4 dosage form performance. With an adequate statistical modelling approach, the design is efficient and allows general conclusions with moderate sample sizes.
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assessment of Levothyroxine Sodium bioavailability recommendations for an improved methodology based on the pooled analysis of eight identically designed trials with 396 drug exposures
Clinical Pharmacokinectics, 2004Co-Authors: Ingeborg Waltersack, Christof Clanget, Reinhard Ding, Christoph Goeggelmann, Vera Hinke, Matthias Lang, Johannes Pfeilschifter, Yorki Tayrouz, Karl WegscheiderAbstract:Assessment of dosage form performance in delivering endogenous compounds, such as hormones, in vivo requires a specific approach. Assessment of relative bioavailability of Levothyroxine Sodium (L-T4) from eight solid preparations, compared with a liquid formulation, by using pharmacological doses, and critical evaluation of trial methodology based on the pooled analysis of individual data. Eight open-label, randomised, single-dose, crossover phase I studies using eight solid L-T4 dosage forms (25, 50, 75, 100, 125, 150, 175, 200μg per tablet; administered total doses 600, 625 or 700μg) and a liquid formulation; assessment of relative bioavailability by 90% confidence intervals for the relative area under the concentration-time curve (AUC) of total thyroxine (TT4), i.e. protein-bound plus free thyroxine, calculated by using the recommended log AUC four-way analysis of variance models for crossover designs. For the pooled analysis, general linear models were applied to assess the validity of model assumptions, to identify potential sources of effect modification, to discuss alternative modelling approaches with respect to endogenous hormone secretion and to give recommendations for future designs and sample sizes. One hundred and sixty-nine healthy males; 29 of these individuals participating in two studies. Single oral doses of L-T4 tablets and the liquid formulation administered after fasting, separated by at least 6 weeks; a total of 396 drug exposures. TT4 AUC from 0 to 48 hours and peak plasma concentration with and without baseline correction. Each study demonstrated equivalence of the tablets to the drinking solution, independent of the chosen analysis model. Sequence effects that could devalidate the chosen crossover approach were not found. Period effects with changing directions that could best be explained by seasonal variation were detected. While the pre-specified method of baseline correction of simply subtracting individual time-zero TT4 values was disadvantageous, the analysis of total AUC could be improved considerably by covariate adjustment for baseline TT4. With this approach, sample sizes could have been substantially reduced or, alternatively, the recommended equivalence ranges could be reduced to ±6%. Conclusion: Using a single pharmacological dose of L-T4 in two-period crossover designs is a safe and reliable procedure to assess L-T4 dosage form performance. With an adequate statistical modelling approach, the design is efficient and allows general conclusions with moderate sample sizes.
Roland Reischl - One of the best experts on this subject based on the ideXlab platform.
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Levothyroxine Sodium revisited a wholistic structural elucidation approach of new impurities via hplc hrms ms on line h d exchange nmr spectroscopy and chemical synthesis
Journal of Pharmaceutical and Biomedical Analysis, 2017Co-Authors: M Ruggenthaler, J Grass, W Schuh, Christian G Huber, Roland ReischlAbstract:Abstract The structural elucidation of unknown pharmaceutical impurities plays an important role in the quality control of newly developed and well-established active pharmaceutical ingredients (APIs). The United States Pharmacopeia (USP) monograph for the API Levothyroxine Sodium, a synthetic thyroid hormone, features two high pressure liquid chromatography (HPLC) methods using UV-VIS absorption detection to determine organic impurities in the drug substance. The impurity profile of the first USP method (“ Procedure 1 ”) has already been extensively studied, however for the second method (“ Procedure 2 ”), which exhibits a significantly different impurity profile, no wholistic structural elucidation of impurities has been performed yet. Applying minor modifications to the chromatographic parameters of USP “ Procedure 2 ” and using various comprehensive structural elucidation methods such as high resolution tandem mass spectrometry with on-line hydrogen-deuterium (H/D) exchange or two-dimensional nuclear magnetic resonance spectroscopy (NMR) we gained new insights about the complex impurity profile of the synthetic thyroid hormone. This resulted in the characterization of 24 compounds previously unknown to literature and the introduction of two new classes of Levothyroxine Sodium impurities. Five novel compounds were unambiguously identified via isolation or synthesis of reference substances and subsequent NMR spectroscopic investigation. Additionally, Collision-Induced Dissociation (CID)-type fragmentation of identified major impurities as well as neutral loss fragmentation patterns of many characterized impurities were discussed.
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Levothyroxine Sodium revisited: A wholistic structural elucidation approach of new impurities via HPLC-HRMS/MS, on-line H/D exchange, NMR spectroscopy and chemical synthesis.
Journal of Pharmaceutical and Biomedical Analysis, 2016Co-Authors: M Ruggenthaler, J Grass, W Schuh, Christian G Huber, Roland ReischlAbstract:Abstract The structural elucidation of unknown pharmaceutical impurities plays an important role in the quality control of newly developed and well-established active pharmaceutical ingredients (APIs). The United States Pharmacopeia (USP) monograph for the API Levothyroxine Sodium, a synthetic thyroid hormone, features two high pressure liquid chromatography (HPLC) methods using UV-VIS absorption detection to determine organic impurities in the drug substance. The impurity profile of the first USP method (“ Procedure 1 ”) has already been extensively studied, however for the second method (“ Procedure 2 ”), which exhibits a significantly different impurity profile, no wholistic structural elucidation of impurities has been performed yet. Applying minor modifications to the chromatographic parameters of USP “ Procedure 2 ” and using various comprehensive structural elucidation methods such as high resolution tandem mass spectrometry with on-line hydrogen-deuterium (H/D) exchange or two-dimensional nuclear magnetic resonance spectroscopy (NMR) we gained new insights about the complex impurity profile of the synthetic thyroid hormone. This resulted in the characterization of 24 compounds previously unknown to literature and the introduction of two new classes of Levothyroxine Sodium impurities. Five novel compounds were unambiguously identified via isolation or synthesis of reference substances and subsequent NMR spectroscopic investigation. Additionally, Collision-Induced Dissociation (CID)-type fragmentation of identified major impurities as well as neutral loss fragmentation patterns of many characterized impurities were discussed.
Peter D Bernardo - One of the best experts on this subject based on the ideXlab platform.
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in vitro dissolution and in vivo bioavailability of commercial Levothyroxine Sodium tablets in the hypothyroid dog model
Journal of Pharmaceutical Sciences, 1990Co-Authors: Ray W Wood, Leo Martis, Amy W Gillum, Theodore J Roseman, Peter D BernardoAbstract:The objective of this study was to determine whether a correlation exists between the rate of in vitro dissolution and bioavailability of Levothyroxine Sodium (T4) tablets. Dissolution versus time profiles for Synthroid, the Flint brand of Levothyroxine Sodium, and two competitors' tablets (brands A and B) were generated using an official dissolution apparatus (USP), and 0.05 M phosphate buffer (pH 7.4) as the medium. These tablets were also utilized in single-dose crossover bioavailability studies in the hypothyroid dog model (n = 6). The average areas under the serum T4 concentration versus time curve from 0 to 8 h (AUC) for Synthroid, brand A, and brand B were 8.22, 6.32, and 8.70 ng-h/mL per dose (μg per kg body weight), respectively. Respective peak serum concentrations (Cmax) for each tablet formulation were 1.26, 1.07, and 1.36 ng/mL per dose. The corresponding dissolution rates, expressed as t50%, were 20.5, 3.06, and 14.1 min, respectively. Data analysis indicated no correlation between dissolution kinetic parameters and the bioavailability parameters AUC and Cmax. However, a linear relationship was observed between dissolution kinetics and both the time to reach maximal serum concentration (tmax) and the observed absorption rate constant (ka).