Excipient metal complexing

However, the use of buffers in parenterals is not always benign, and numerous instances have been summarized where buffers or other excipients have caused stability problems.For instance, the com-plexation of Ca(II) and Al(III) with phosphate buffer solutions has been studied at great length, as well as the kinetic characteristics of the subsequent precipitation of calcium and aluminum phosphate salts. The use of metal complexing excipients, such as citric... 

The theory and application of this fluorescence method have been discussed in detail by LePecq and others (3,8). The assay requires that there is sufficient ionic strength to minimize ionic binding (e.g., O.IM sodium chloride), that the pH is 4-10, that no heavy metals are present, that the fluorescence is not enhanced on binding to other excipients (e.g., proteins) and that at least portions of the nucleic acids are not complexed. These requirements can usually he met when dealing with recombinant products in some cases the samples must he manipulated to create the appropriate conditions. In the intercalative method of dye binding, proteins rarely interfere with the assay, and procedures have been developed to remove the few interferences they may cause (e.g., the use of heparin or enzymatic digestion of the protein 9). 

Trace metal ions can affect stability and can arise from the bulk drug, formulation excipients or glass containers. The effect of metal ions on the solution stability of fosinopril sodium has been reported (Thakur et al. 1993). In this case, the metal ions were able to provide, through complexation, a favourable reaction pathway. 

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