Drug product chelating agents

One of the critical factors in excipient selection and concentration is the effect on preferential hydration of the biopharmaceutical product [53, 54], Preferential hydration refers to the hydration layers on the outer surface of the protein and can be utilized to thermodynamically explain both stability enhancement and denatur-ation. Typical excipients used in protein formulations include albumin, amino acids, carbohydrates, chelating and reducing agents, cyclodextrins, polyhydric alcohols, polyethylene glycol, salts, and surfactants. Several of these excipients increase the preferential hydration of the protein and thus enhance its stability. Cosolvents need to be added in a concentration that will ensure their exclusion from the protein surface and enhance stability [54], A more comprehensive review of excipients utilized for biopharmaceutical drug products is available elsewhere [48],... 

Buffers can also be provided in parenteral formulations to ensure the required pH needed for solubility and/or stability considerations. Other excipients included in parenteral products are preservatives (e.g., benzyl alcohol, p-hydroxybenzoate esters, and phenol), antioxidants (e.g., ascorbic acid, sodium bisulfite, sodium metabisulfite, cysteine, and butyl hydroxy anisole), surfactants (e.g., polyoxyethylene sorbitan monooleate), and emulsifying agents (e.g., polysorbates). An inert gas (such as nitrogen) can also be used to enhance drug stability. Stability and solubility can also be enhanced by the addition of complexation and chelating agents such as the ethylenediaminetetraacetic acid salts. For a more detailed list of approved excipients in parenteral products, the reader should consult the monographs within the USP. 

The use of anionic polymers coupled to catalytic enzymes or to catalytic chelating agents [105, 106], degradation-controUed drug elution, provides a complex system that behaves in catalytic conversion, selective transport enhancement and enrichment of products in simUar fashion to membrane reactors. Articles, deal with WSP hquid membrane reactors, were not found, nevertheless this direction is very outlook in the application of the BAHLM systems. 

By January 1991, 50 orphan products had been approved for the treatment of 58 rare conditions. Companies had received 12 million in tax credits for orphan research. The classic orphan drug cases had been sorted out. For example, trientine hydrochloride, H2N(CH2)2-NH(CH2)2NH(CH2)2NH2.HC1, a chelating agent used to remove excess copper in Wilson s disease for patients who... 

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