Excipients for Protein Drugs

Yatin R. Gokarn, Andrew Kosky, Eva Kras, Arnold McAuley, and Richard L. Remmele, Jr. 

Department of Pharmaceutics, Amgen Inc., Thousand Oaks, California, U.S.A. 

Excipients are additives that are included in a formulation, because they either impart or enhance the stability, delivery, and manufacturability of a drug product. Regardless of the reason for their inclusion, excipients are an integral component of a drug product and therefore need to be safe and well tolerated by patients. For protein drugs, the choice of excipients is particularly important because they can affect both efficacy and immunogenicity of the drug. Hence, protein formulations need to be developed with appropriate selection of excipients that afford suitable stability, safety, and marketability. 

Protein-based drugs have been formulated mainly as stable liquids or in cases where liquid stability is limiting as lyophilized dosage forms to be reconstituted with a suitable diluent prior to injection. This is because their delivery has been limited primarily to the parenteral routes of intravenous (IV), subcutaneous (SC), or intramuscular (IM) administration. There are a few drugs that have been developed for pulmonary delivery, such as rhDNase (Pulmozyme ) and an inhalable formulation of insulin (e.g., Exubra ). However, even such drugs have been formulated as either liquid or lyophilized or spray-dried powders. This chapter will focus only on excipients that are applicable to liquid and lyophilized protein formulations. 

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Brewster, M.E., M.S. Hora, J.W. Simpkins, and N. Bodor, Use of 2-hydroxy propyl-beta-cyclodextrin as a solubilizing and stabilizing excipient for protein drugs. Pharm Res, 1991. 8(6) 792-5. 

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