The Experts below are selected from a list of 131241 Experts worldwide ranked by ideXlab platform
John F Carpenter - One of the best experts on this subject based on the ideXlab platform.
-
optimizing Storage Stability of lyophilized recombinant human interleukin 11 with disaccharide hydroxyethyl starch mixtures
Journal of Pharmaceutical Sciences, 2004Co-Authors: William Garzonrodriguez, Theodore W Randolph, Rebecca L Koval, Suchart Chongprasert, Sampathkumar Krishnan, Nicholas W Warne, John F CarpenterAbstract:Abstract Optimal Storage Stability of a protein in a dry formulation depends on the Storage temperature relative to the glass transition temperature ( T g ) of the dried formulation and the structure of the dried protein. We tested the hypothesis that optimizing both protein structure and T g —by freeze-drying recombinant human interleukin-11 (rhIL-11) with mixtures of disaccharides and hydroxyethyl starch (HES)—would result in increased Storage Stability compared with the protein lyophilized with either disaccharide or hydroxyethyl starch alone. The secondary structure of the protein in the dried solid was analyzed immediately after lyophilization and after Storage at elevated temperatures by infrared spectroscopy. After rehydration, aggregation was monitored by size exclusion chromatography. Oxidation levels and cleavage products were quantified by reversed-phase chromatography. For the formulation with HES alone, which has a relatively high T g , Storage Stability of rhIL-11 was poor, because HES failed to inhibit lyophilization-induced unfolding. The sugar formulations inhibited unfolding, and had intermediate T g values and Storage stabilities. Addition of hydroxyethyl starch to sucrose or trehalose increased T g without affecting the capacity of the sugar to inhibit protein unfolding during lyophilization. Optimal Storage Stability of lyophilized rhIL-11 was achieved by using a mixture of disaccharide and polymeric carbohydrates. © 2004 Wiley-Liss, Inc. and the American Pharmacists Association
-
a specific molar ratio of stabilizer to protein is required for Storage Stability of a lyophilized monoclonal antibody
Journal of Pharmaceutical Sciences, 2001Co-Authors: Jeffrey L Cleland, Brent S Kendrick, Janet Yufeng Yang, Tzunghorng Yang, David E Overcashier, Dennis Brooks, John F CarpenterAbstract:The selection of the appropriate excipient and the amount of excipient required to achieve a 2-year shelf-life is often done by using iso-osmotic concentrations of excipients such as sugars (e.g., 275 mM sucrose or trehalose) and salts. Excipients used for freeze-dried protein formulations are selected for their ability to prevent protein denaturation during the freeze-drying process as well as during Storage. Using a model recombinant humanized monoclonal antibody (rhuMAb HER2), we assessed the impact of lyoprotectants, sucrose, and trehalose, alone or in combination with mannitol, on the Storage Stability at 40 degrees C. Molar ratios of sugar to protein were used, and the Stability of the resulting lyophilized formulations was determined by measuring aggregation, deamidation, and oxidation of the reconstituted protein and by infrared (IR) spectroscopy (secondary structure) of the dried protein. A 360:1 molar ratio of lyoprotectant to protein was required for Storage Stability of the protein, and the sugar concentration was 3-4-fold below the iso-osmotic concentration typically used in formulations. Formulations with combinations of sucrose (20 mM) or trehalose (20 mM) and mannitol (40 mM) had comparable Stability to those with sucrose or trehalose alone at 60 mM concentration. A formulation with 60 mM mannitol alone provided slightly less protection during Storage than 60 mM sucrose or trehalose. The disaccharide/mannitol formulations also inhibited deamidation during Storage to a greater extent than the lyoprotectant formulations alone. The reduction in aggregation and deamidation during Storage correlated directly with inhibition of unfolding during lyophilization, as assessed by IR spectroscopy. Thus, it appears that the protein must be retained in its native-like state during freeze-drying to assure Storage Stability in the dried solid. Long-term studies (23-54 months) performed at 40 degrees C revealed that the appropriate molar ratio of sugar to protein stabilized against aggregation and deamidation for up to 33 months. Therefore, long-term Storage at room temperature or above may be achieved by proper selection of the molar ratio and sugar mixture. Overall, a specific sugar/protein molar ratio was sufficient to provide Storage Stability of rhuMAb HER2.
-
a specific molar ratio of stabilizer to protein is required for Storage Stability of a lyophilized monoclonal antibody
Journal of Pharmaceutical Sciences, 2001Co-Authors: Jeffrey L Cleland, Brent S Kendrick, Janet Yufeng Yang, Tzunghorng Yang, David E Overcashier, Dennis Brooks, John F CarpenterAbstract:Abstract The selection of the appropriate excipient and the amount of excipient required to achieve a 2‐year shelf‐life is often done by using iso‐osmotic concentrations of excipients such as sugars (e.g., 275 mM sucrose or trehalose) and salts. Excipients used for freeze‐dried protein formulations are selected for their ability to prevent protein denaturation during the freeze–drying process as well as during Storage. Using a model recombinant humanized monoclonal antibody (rhuMAb HER2), we assessed the impact of lyoprotectants, sucrose, and trehalose, alone or in combination with mannitol, on the Storage Stability at 40°C. Molar ratios of sugar to protein were used, and the Stability of the resulting lyophilized formulations was determined by measuring aggregation, deamidation, and oxidation of the reconstituted protein and by infrared (IR) spectroscopy (secondary structure) of the dried protein. A 360:1 molar ratio of lyoprotectant to protein was required for Storage Stability of the protein, and the sugar concentration was 3–4‐fold below the iso‐osmotic concentration typically used in formulations. Formulations with combinations of sucrose (20 mM) or trehalose (20 mM) and mannitol (40 mM) had comparable Stability to those with sucrose or trehalose alone at 60 mM concentration. A formulation with 60 mM mannitol alone provided slightly less protection during Storage than 60 mM sucrose or trehalose. The disaccharide/mannitol formulations also inhibited deamidation during Storage to a greater extent than the lyoprotectant formulations alone. The reduction in aggregation and deamidation during Storage correlated directly with inhibition of unfolding during lyophilization, as assessed by IR spectroscopy. Thus, it appears that the protein must be retained in its native‐like state during freeze–drying to assure Storage Stability in the dried solid. Long‐term studies (23–54 months) performed at 40°C revealed that the appropriate molar ratio of sugar to protein stabilized against aggregation and deamidation for up to 33 months. Therefore, long‐term Storage at room temperature or above may be achieved by proper selection of the molar ratio and sugar mixture. Overall, a specific sugar/protein molar ratio was sufficient to provide Storage Stability of rhuMAb HER2. © 2001 Wiley‐Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 90:310–321, 2001
-
optimization of Storage Stability of lyophilized actin using combinations of disaccharides and dextran
Journal of Pharmaceutical Sciences, 2000Co-Authors: Dean S Allison, Kim Middleton, Ashley Davis, Mark C Manning, Theodore W Randolph, John F CarpenterAbstract:Abstract The Storage Stability of a dry protein depends on the structure of the dried protein, as well as on the Storage temperature relative to the glass transition temperature of the dried preparation. Disaccharides are known to preserve the native conformation of a dried protein; however, the resulting T g of the sample may be too low ensure adequate Storage Stability. On the other hand, formulations dried with high molecular weight carbohydrates, such as dextran, have higher glass transition temperatures, but fail to preserve native protein conformation. We tested the hypothesis that optimizing both protein structure and T g by freeze‐drying actin with mixtures of disaccharides and dextran would result in increased Storage Stability compared to actin dried with either disaccharide or dextran alone. Protein structure in the dried solid was analyzed immediately after lyophilization and after Storage at elevated temperatures with infrared spectroscopy, and after rehydration by infrared and circular dichroism spectroscopy. Structural results were related to the polymerization activity recovered after rehydration. Degradation was noted with Storage for formulations containing either sucrose, trehalose, or dextran alone. Slight increases in T g observed in trehalose formulations compared to sucrose formulations did not result in appreciable increases in Storage Stability. Addition of dextran to sucrose or trehalose increased formulation T g without affecting the capacity of the sugar to inhibit protein unfolding during lyophilization and resulted in improved Storage Stability. Also, dextran provides an excellent amorphous bulking agent, which can be lyophilized rapidly with formation of strong, elegant cake structure. These results suggest that the strategy of using a mixture of disaccharide and polymeric carbohydrates can optimize protein Storage Stability. © 2000 Wiley‐Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 89: 199–214, 2000
-
physical factors affecting the Storage Stability of freeze dried interleukin 1 receptor antagonist glass transition and protein conformation
Archives of Biochemistry and Biophysics, 1996Co-Authors: Byeong S Chang, Robert M Beauvais, Aichun Dong, John F CarpenterAbstract:Abstract The effects of glass transition of, and protein conformation in, the dried solid on the Storage Stability of freeze-dried recombinant human interleukin-1 receptor antagonist (rhIL-1ra) were examined. Glass transition is a temperature-dependent phenomenon. Amorphous materials become hard and brittle at temperatures below their characteristic glass transition temperatures (Tg) such that diffusion of molecules along the matrix is not sufficient to cause large-scale structural changes. To ascertain the importance of the glass transition in protein Storage Stability, we compared 10 different lyophilized rhIL-1ra formulations, with Tgs ranging from 20 to 56°C, during several weeks of Storage at temperatures above and below the samples’ Tgs. Protein degradation, both deamidation and aggregation, was greatly accelerated at temperatures above Tg, but for some formulations also arose below Tg. Thus, Storage of dried proteins below the Tg is necessary but not sufficient to ensure long-term Stability. To examine the effects of protein structure in the dried solid, we prepared formulations with various sucrose concentrations, all of which had a Tg = 66 ± 2.5°C. With infrared spectroscopy, we determined that the protein lyophilized with ≤1% sucrose was unfolded in the initial dried solid. In contrast, in those formulations with ≥5% sucrose, conformational change was inhibited during lyophilization. When stored at 50°C, degradation of the freeze-dried protein varied inversely with sucrose concentration. These results indicate that structural changes arising during the lyophilization process led to damage during subsequent Storage, even if the Storage temperature was less than the Tg. Together the results of these studies document that to obtain optimum Stability of dried rhIL-1ra it was necessary to inhibit conformational change during lyophilization and to store at temperatures below the Tg of the dried formulation.
Baodong Xing - One of the best experts on this subject based on the ideXlab platform.
-
viscous properties Storage Stability and their relationships with microstructure of tire scrap rubber modified asphalt
Construction and Building Materials, 2015Co-Authors: Ming Liang, Baodong XingAbstract:Abstract Recycled-polymer modified asphalt has been extensively used in road construction, especially the recycled tire scrap rubber-modified asphalt (TSRMA). However, the main problem during the application of TSRMA is poor Storage Stability which finally affects the service performance of the pavement. The objective of this work is to evaluate viscous properties, Storage Stability and morphology of TSRMA and to reveal the relationship of microstructure with rheological behavior and Storage Stability. With this aim, two different penetration grade asphalts were modified by rubber particles with various mean diameter in a four-paddle mixer at 170 °C. Steady state flow measurements, frequency sweep tests in linear viscoelastic region, Storage Stability tests as well as fluorescence microscopy were carried out on mixes. Rheological evaluation reveals that the addition of tire scrap rubber to asphalt lead to a significant increase in viscosity at 60 °C, improving rutting or permanent deformation resistance. Furthermore, the increase in particle size causes an enhancement in viscosity and the steady flow behavior tend to turn into non-Newtonian fluid with increasing particle size and temperature. Storage tests presented that the viscosity of samples obtained from the bottom section of a tube are always higher and the difference also becomes significant as the increase of rubber particles size, tending to poor Stability. Fluorescence microscopy shows that dispersed particles in asphalt are the elongated features or strip-type and the aspect ratio (length/diameter) increases with particle size. In addition, smaller particle tend to be unobvious in matrix under microscopy view, indicating improved compatibility between rubber and asphalt.
-
investigation of the rheological properties and Storage Stability of cr sbs modified asphalt
Construction and Building Materials, 2015Co-Authors: Ming Liang, Xue Xin, Weiyu Fan, Hui Luo, Xiaobo Wang, Baodong XingAbstract:Abstract The rheological properties and Storage Stability of CR/SBS modified asphalt have been investigated in this study. Crumb rubber (CR) as well as SBS was blended with asphalt having different chemical composition to prepare CR/SBS modified asphalt by high-shear mixer. Linear viscoelastic and viscous measurements, fluorescence microscopy as well as Storage Stability tests were performed on unmodified and CR/SBS modified asphalt. The results revealed that the addition of CR/SBS to asphalt produces a remarkable improvement in viscoelastic characteristics and viscosity compared with neat asphalt. Consequently, an enhanced resistance to permanent deformation is expected in road. Crumb rubber replacing parts of SBS to produce CR/SBS modified asphalt is feasible because failure temperature, moduli and viscosity undergo a significantly increase when the dosage of SBS exceeds 1%. The chemical composition of base asphalt for this special modification is crucial. In other words, moderate asphaltenes and high aromatics are suggested in order to achieve desired rheological properties. CR/SBS modified asphalt appears obvious phase separation at the storing period resulting from coalescence of SBS particle at the top of sample and sedimentation of rubber particles at the bottom. Thus, CR/SBS modified asphalt must be used swiftly after which has been produced owing to its poor Storage Stability. Anyhow, crumb rubber could be an alternative for reducing use of virgin SBS from economic and environmental point of view.
Helena Janik - One of the best experts on this subject based on the ideXlab platform.
-
Development of methods improving Storage Stability of bitumen modified with ground tire rubber: A review
Fuel Processing Technology, 2017Co-Authors: Maciej Sienkiewicz, Kaja Borzędowska-labuda, Artur Wojtkiewicz, Helena JanikAbstract:The following paper presents an overview of methods for improving the Storage Stability at high temperature of rubber modified bitumen. The Storage Stability of the rubber modified bitumen can be improved by using a various types of modifiers that form the bonds between the components of these binders. The increase in Stability can also be achieved by using crumb rubber surface-activated by furaldehyde or ground tire rubber (GTR) treated by gamma irradiation or modified by devulcanization process. The Storage Stability of rubber modified bitumen can be also improved by preparing compositions obtained from GTR and other components leading to a reduction in density as compared to unmodified GTR. unmodified GTR.
Ming Liang - One of the best experts on this subject based on the ideXlab platform.
-
viscous properties Storage Stability and their relationships with microstructure of tire scrap rubber modified asphalt
Construction and Building Materials, 2015Co-Authors: Ming Liang, Baodong XingAbstract:Abstract Recycled-polymer modified asphalt has been extensively used in road construction, especially the recycled tire scrap rubber-modified asphalt (TSRMA). However, the main problem during the application of TSRMA is poor Storage Stability which finally affects the service performance of the pavement. The objective of this work is to evaluate viscous properties, Storage Stability and morphology of TSRMA and to reveal the relationship of microstructure with rheological behavior and Storage Stability. With this aim, two different penetration grade asphalts were modified by rubber particles with various mean diameter in a four-paddle mixer at 170 °C. Steady state flow measurements, frequency sweep tests in linear viscoelastic region, Storage Stability tests as well as fluorescence microscopy were carried out on mixes. Rheological evaluation reveals that the addition of tire scrap rubber to asphalt lead to a significant increase in viscosity at 60 °C, improving rutting or permanent deformation resistance. Furthermore, the increase in particle size causes an enhancement in viscosity and the steady flow behavior tend to turn into non-Newtonian fluid with increasing particle size and temperature. Storage tests presented that the viscosity of samples obtained from the bottom section of a tube are always higher and the difference also becomes significant as the increase of rubber particles size, tending to poor Stability. Fluorescence microscopy shows that dispersed particles in asphalt are the elongated features or strip-type and the aspect ratio (length/diameter) increases with particle size. In addition, smaller particle tend to be unobvious in matrix under microscopy view, indicating improved compatibility between rubber and asphalt.
-
investigation of the rheological properties and Storage Stability of cr sbs modified asphalt
Construction and Building Materials, 2015Co-Authors: Ming Liang, Xue Xin, Weiyu Fan, Hui Luo, Xiaobo Wang, Baodong XingAbstract:Abstract The rheological properties and Storage Stability of CR/SBS modified asphalt have been investigated in this study. Crumb rubber (CR) as well as SBS was blended with asphalt having different chemical composition to prepare CR/SBS modified asphalt by high-shear mixer. Linear viscoelastic and viscous measurements, fluorescence microscopy as well as Storage Stability tests were performed on unmodified and CR/SBS modified asphalt. The results revealed that the addition of CR/SBS to asphalt produces a remarkable improvement in viscoelastic characteristics and viscosity compared with neat asphalt. Consequently, an enhanced resistance to permanent deformation is expected in road. Crumb rubber replacing parts of SBS to produce CR/SBS modified asphalt is feasible because failure temperature, moduli and viscosity undergo a significantly increase when the dosage of SBS exceeds 1%. The chemical composition of base asphalt for this special modification is crucial. In other words, moderate asphaltenes and high aromatics are suggested in order to achieve desired rheological properties. CR/SBS modified asphalt appears obvious phase separation at the storing period resulting from coalescence of SBS particle at the top of sample and sedimentation of rubber particles at the bottom. Thus, CR/SBS modified asphalt must be used swiftly after which has been produced owing to its poor Storage Stability. Anyhow, crumb rubber could be an alternative for reducing use of virgin SBS from economic and environmental point of view.
C Gallegos - One of the best experts on this subject based on the ideXlab platform.
-
thermo rheological behaviour and Storage Stability of ground tire rubber modified bitumens
Fuel, 2004Co-Authors: F J Navarro, P Partal, F J Martinezboza, C GallegosAbstract:This paper deals with the thermo-rheological behaviour at in-service and handling temperatures (i.e. pumping, mixing, compaction, etc.) of bitumens modified by 9 wt% crumb tire rubber. The use of waste tire rubbers as bitumen modifiers can contribute to alleviate pollution problems derived from discarding scrap tires. Thus, the mechanical characteristics and Storage Stability of crumb tire rubber modified bitumens (CTRMBs) have been studied as a function of rubber particle size. The addition of ground tire rubber to bitumen increases both the linear viscoelastic moduli and viscosity, at high in-service temperatures, and reduces the Storage and loss moduli, at low temperatures, resulting in a more flexible binder in this temperature region. As a consequence, a crumb tire rubber modified bitumen displays enhanced mechanical properties, which improves its resistance to both rutting and fatigue cracking. The presence of insoluble non-spherical particles affects the flow behaviour observed at high temperatures. From the experimental results obtained, it may be concluded that the use of rubber particle sizes lower than 0.35 mm and high shear rates during manufacturing operations is highly recommended. Storage Stability of CTRMBs decreases with increasing particle size and Storage temperature and takes place by the precipitation of the non-dissolved rubber particles. Only the sample containing rubber particles with a mean particle size of 0.29 mm remains stable under the selected Storage conditions.
