Chelating agents antioxidants

Various additives are needed for stability, sterility, and isotonicity, including antimicrobial preservatives, antioxidants, chelating agents, and buffers. 

The user enters all known data on the solubility (aqueous and non-aqueous), stability in specified solutions, compatibility, pAia, and molecular properties of the active ingredient (molecular weight, log/, etc.). As with the system for tablet formulation, the data may be numerical or symbolic. All relevant properties of additives used in parenteral formulation (e.g., buffers, antioxidants, chelating agents, antimicrobials, and tonicity adjusters) are present in the knowledge base. 

As a guide to formulation development, studies should be undertaken to evaluate the contribution of candidate excipients, including preservatives, antioxidants, chelating agents, cosolvents, and buffers on compound stability and solubility. This is particularly important in the development of suspensions for nebulization. Compatibility with packaging components also needs to be considered as a matter of priority. Peptides and proteins in particular are notorious in their ability to adsorb onto a variety of surfaces, particularly plastic. 

The antioxidant synergists enhance the effect of antioxidants. Chelating agents like ethylenediaminetetraacetic acid (EDTA) are commonly added to parenterals. They may reduce oxidative damage by forming complexes with oxidative metal ion catalysts. Chelating agents are further discussed in Section 14.2.6. 

Doverphos. [Dover] Phosphites heat and color stabilizers, antioxidants, chelating agents for plastics, rubber lubricant additives aids curing and hardening in epoxies. 

Certain compounds, known as chelating agents (qv), react synergisticaHy with many antioxidants. It is beheved that these compounds improve the functional abiUties of antioxidants by complexing the metal ions that often initiate free-radical formation. Citric acid and ethylenediaminetetraacetic acid [60-00-4] (EDTA), C2QH2gN20g, are the most common chelating agents used (22). 

Mineral oil and paraffins should not be used, because these are not metabolized and may irritate tissue. Various other additives are needed for stabiUty, stefihty, and isotonicity antimicrobial preservatives, antioxidants (qv), chelating agents (qv), and buffers. No parenteral container material is completely inert to parenteral solvent systems. 

The rate of peroxide decomposition and the resultant rate of oxidation are markedly increased by the presence of ions of metals such as iron, copper, manganese, and cobalt [13]. This catalytic decomposition is based on a redox mechanism, as in Figure 15.2. Consequently, it is important to control and limit the amounts of metal impurities in raw rubber. The influence of antioxidants against these rubber poisons depends at least partially on a complex formation (chelation) of the damaging ion. In favor of this theory is the fact that simple chelating agents that have no aging-protective activity, like ethylene diamine tetracetic acid (EDTA), act as copper protectors. 

As metal ions catalyze peiroxidation reactions, glass-distilled water should be used and chelating agents can be added to the medium. (5) The dispersions should not be exposed to y irradiation. (6) Antioxidant can be added to the system. a-Tocopherol, buty-lated hydroxytoluene, butyl hydroxyanisole, and ascorbic acid have been proposed as antioxidants. 

In addition to phenolic substances, there are other components present in foods which have no antioxidant activity of their own, but which increase that of phenolic antioxidants. They are called synergists, and they should be accounted for in any discussion of antioxidant activity. Polyvalent organic acids, amino acids, phospholipids (lecithin) and various chelating agents belong to this group. Proteins may modify the efficiency of antioxidants as they react with the reaction products of both antioxidants and synergists. 

Administration of synthetic antioxidants and/or chelating agents that suppress iron ion-dependent free-radical reactions. Some enzyme inhibitors may be appropriate here, for example, xanthine oxidase inhibitors. 

In general, such studies are carried out by placing the drug in a solution of the additive. These can be (and usually are) a heavy metal (with or without chelating agents present) or an antioxidant (in either oxygen or... 

Ponka et al. [372] showed that pyridoxal isonicotinoyl hydrazone (PIH, Figure 19.23) is an iron chelating agent. Numerous studies showed the possibility of using this chelator for the treatment of iron overload disease [373], In subsequent studies the antioxidant activity of PIN has been confirmed. For example, Hermes-Lima et al. [374,375] showed that PIN protected plasmid pUC-18 DNA and 2-deoxyribose against hydroxyl radical damage. 

Oxidations are catalyzed by acids, bases, pH values that are higher than the optimum, polyvalent metal ions, peroxides, hydroperoxides, and exposure to oxygen and ultraviolet (UV) illumination. These reactions may necessitate the use of antioxidant chemicals, inert atmospheres, and opaque packaging. Chelating agents... 

Malic acid Antioxidant, buffering agent, flavoring agent, chelating agent The powder form has a strongly acid taste and is freely soluble in ethanol and water. However, aqueous solutions are mildly corrosive to carbon steels... 

Fumaric acid Acidulant, flavoring agent, chelating agent synergist Exhibits synergism when used in combination with other true antioxidants. Low aqueous solubility... 

Citric acid Buffering agent, antioxidant synergist, chelating agent, flavor enhancer On storage, sucrose may crystallize from syrups in the presence of citric acid. Dilute aqueous solutions may ferment on standing. Tart acid taste... 

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