Formulation support degradation products

Thus, the nonulosaminic acids were formulated as aldol condensation products of a hexosamine with pyruvic acid. This speculative concept received its first support with the isolation of A -acetyl-n-glucosamine as a degradation product of A -acetylneuraminic acid. These degradations employed nickel acetate plus pyridine or mild alkah for ten minutes. Besides A -acetyl-n-glucosamine and a number of unidentified degradation products, pyruvic acid was produced and was isolated as its (2,4-di-nitrophenyl) hydrazone. 

There is evidence to support the view that products can be overdried. Some water may be needed to maintain the structural stability of the biological and removal of this may lead to destabilization. Extended drying of insulin resulted in a rise in the level of degradation products detected by reverse phase HPLC analysis, as shown in Table 4 [17]. Other researchers have noted loss of activity in influenza virus with excessive drying [18]. The optimum level of dryness should be determined for each material to be dried [19], where feasible, given the number of formulations to be dried. 

Forced degradation/stress studies elucidate the inherent stability characteristics of the molecule under study and determine its degradative pathways. Forced degradation studies are needed to support method validation, determine product protection requirements, and guide formulation development. 

In the study of thermal stability, accelerated testing in the form of elevated temperatures has been used by many pharmaceutical companies to minimize time involved in the testing process. This procedure is only valid for simple formulations in which the single major ingredient is broken down by a thermal reaction. In practice, regulatory authorities demand that a shelf-life determined by extrapolation of accelerated test data should be supported by actual stability data obtained by normal temperature storage (Carstensen, 1995). This is because degradation of a product by microbial contamination may well be inhibited at elevated temperatures. 

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