ABSTRACT
Formulation of peptide and protein drugs is very different from the formulation of traditional drugs in many ways. Unlike traditional drugs, proteins have primary, secondary, tertiary, and quaternary structures, and thus, degradation of proteins is not a simple one-step reaction. As discussed in Chapter 3, multiple inactivation pathways exist for the degradation of peptides and proteins. Furthermore, the products of these degradation reactions may not be easily detected by any one analytical technique. Also, accelerated stability studies for shelf-life determination may be more dif- cult to apply for peptide and protein drugs (Nail, Jiang, Chongprasert, & Knopp, 2002). Formulation development will include a consideration of several factors such as structure of the protein, factors affecting its physical and chemical stability, and means of stabilization (Wang, 1999). A formulation scientist involved in formulation or product development for peptide and protein drugs must have a strong background in protein chemistry in addition to physical pharmacy and formulation principles. Also, support of a strong bioanalytical group is a must for successful formulation development. Table 4.1 provides a listing of some peptide and protein products that are currently on the market for parenteral administration and are obtained from natural or synthetic sources, and Table 4.2 provides a listing of some recombinant proteins on the market. Only a few products are listed in these tables, but a more complete list is available in other publications (PDR Staff, 2014; Spada & Walsh, 2005), and some of the other recombinant proteins approved more recently are discussed in Chapter 1. A list of excipients used in these products is also included. The monoclonal antibodies on the market and the excipients included in their formulation are listed separately in Table 1.1.
