Degradation mechanisms products

Repeat dose pharmacokinetic studies were undertaken in Sprague-Dawley rats and in monkeys. Biodistribution studies were carried out in both normal and knockout mice, with the majority of product distributed to the liver. No specific studies on product metabolism or excretion were undertaken, as the protein is almost certainly degraded via normal protein degradation mechanisms. 

Finally, it should be remembered that lifetime is not necessarily measured in time. For some products and some degradation mechanisms it could be the number of cycles of use, or, in automotive applications, the number of kilometres driven. 

More recently, polyesters with beneficial degradation products (salicylic acid) have been produced to promote healing through enhanced regeneration of tissue [10]. Degradation mechanisms relevant to medical applications include... 

Serajuddin et al. [19] reported that the degradation pathway of prevastatin sodium was directly linked to the micro-pH environment within the formulation. Under neutral conditions (pH 6.5), the statin formed two degradation products, a cyclic lactone and an internal hydroxyl rearrangement product. However, as the pH was increased to 9.9 with the incorporation of magnesium oxide into the blend, the only degradation mechanism involved the formation of the cleavage product, 2-methylpropanoic acid. This latter approach of increasing the... 

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. 

---