Excipients attributes

For any new excipients, APIs or drug products (where new does not necessarily mean novel, but new to the receiving site) there are additional testing criteria, e.g. supplier audits, third-party contract laboratory audits, analytical method transfers, sample management/tracking, etc. For those key excipients, where there is on-site historical experience, it still behoves both parties to check whether the local grade/supplier used by the CMO is equivalent to that used by the supplier (Worsham, 2010). There are many examples of differences in excipient physical properties, e.g. particle size, which have been attributed to different excipient sources that could ultimately impact on the performance of those excipients in formulated products (Frattini and Simioni, 1984 Dansereau and Peck, 1987 Phadke et al., 1994 Lin and Peck, 1994). 

Excipients play a key role in oxidation, either as a primary source of oxidants, trace amounts of metals, or other contaminants. Auto-oxidation of diethylstilbes-terol to the peroxide and conjugated quinone degradation products was attributable to the presence of colloidal silicon dioxide, used as a glidant in solid oral dosage forms [48]. This was ascribed to the fact that silicon dioxide can act as a Lewis acid (an election acceptor or oxidising agent), under anhydrous conditions. 

Hartauer et al. [58] reported that peroxide residues in povidone (binder) and crospovidone (disintegrant) were attributable to the formation of the A-oxide oxidation product of raloxifene. The authors correlated residual levels of peroxide in the excipients with A-oxide formation and thereby gained understanding of the degradation mechanism. A radical-initiated oxidation mechanism would be expected to show a typical S -shaped autocatalytic curve, whereas these curves showed fickian kinetics that is, rapid initial formation of the A-oxide followed by a plateauing of the rate, with consumption of the peroxides, leading to a slowing of the reaction rate. 

In most instances the specimens will be self-evident (e.g., samples of blood, plasma, serum, urine, spinal fluid, aqueous humor, organs, tissues, and tissue fractions that are taken from a test system with the intention of performing an examination or analysis). In other instances the definition may not be as clear. For example, the assay plates used in the mammalian cell transformation assay and the mammalian point mutation assay are considered specimens even though they bear many of the attributes of a test system. For these assays, the originally plated cells plus media and excipients are the test system. After treatment with the test or... 

Allergic contact dermatitis from transdermal estrogen has been described in Korea, where the reaction was found to be due to 17-P-estradiol itself and not to an excipient (226). In some cases, allergic reactions and systemic contact dermatitis are clearly attributable to the patch material or to excipients. Even natural estradiol given in this way can occasionally cause hypersensitivity reactions, as determined by patch tests (227). 

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