Pathways of Chemical Degradation

Drug substances used as pharmaceuticals have diverse molecular structures and are, therefore, susceptible to many and variable degradation pathways. Possible degradation pathways include hydrolysis, dehydration, isomerization and racemization, elimination, oxidation, photodegradation, and complex interactions with excipients and other drugs. It would be very useful if we could predict the chemical instability of a drug based on its molecular structure. This would help both in the design of stability studies and, at the earliest 

the major-degradation pathways in relation to molecular structure are discussed 

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T. J. Ahern and M. J. Manning, Stability of Protein Pharmaceuticals, Part A, Chemical and Physical Pathways of Protein Degradation, Plenum Press, New York, 1992. 

C. Oliyai, R. T. Borchardt, Chemical Pathways of Peptide Degradation. IV. Pathways, Kinetics, and Mechanism of Degradation of an Aspartyl Residue in a Model Hexapeptide , Pharm. Res. 1993, 10, 95- 102. 

K. Patel, R. T. Borchardt, Deamidation of Asparaginyl Residues in Proteins A Potential Pathway for Chemical Degradation of Proteins in Lyophihzed Dosage Form , J. Parent. Sci. Technol. 1990,44, 300-301. 

Oliyai C, Borchardt RT. Chemical pathways of peptide degradation. IV. Pathways, kinetics, and mechanism of degradation of an aspartyl residue in a model hexapeptide. Pharm Res 1993 10(1) 95-102. 

Patel K, Borchardt RT. Chemical pathways of peptide degradation. III. Effect of primary sequence on the pathways of deamidation of asparaginyl residues in hexapeptides. Pharm Res 1990 7(8) 787-793. 

Li, S. Schoneich, C. Wilson, G. Borchardt, R. Chemical pathways of peptide degradation. V. Ascorbic acid promotes rather than inhibits the oxidation of methionine to methionine sulfoxide in small model peptides. Pharm. Res. 1993, 10, 1572-1579. 

Figure 11.7 Schematic of the major pathways of protein degradation, which may be physical or chemical in origin.

Fig. 10 Pathways of NO degradation yield nitrite via a variety of chemical reactions...

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