Formulation of pharmaceuticals to deliver safe, stable active drug products is crucial to both patient and manufacturer. Multifunctional excipients, such as albumin, incorporated into the formulation process facilitate the stabilization of the drug product from degradation and assist in the administration and release of the active component.
The ability of excipients to stabilize and protect an active pharmaceutical ingredient (API) against degradation has caused excipient selection to become more important early in the drug-development process. During manufacturing, transport, and storage, the API can be exposed to a variety of stresses (e.g., temperature variation, pH changes, shear stresses, and freezing) that promote protein degradation, such as denaturation and aggregation. With the potential to increase the immunogenicity and decrease the efficacy and shelf life of the protein drug product, protein stability is a key issue in the final product. Investigating excipient-drug interaction during preformulation stages means that excipient selection, which achieves the desired properties for the final drug product, can be thoroughly explored (1).Increasing regulatory pressure on the safety, purity, and standardization of excipients has seen the formation of the International Pharmaceutical Excipients Council (IPEC), which defines excipients as substances other than the active drug that have been appropriately evaluated for safety and are included in a drug-delivery system to aid processing of the system during manufacture, and enhance any other attribute of the overall safety and effectiveness of the drug product during storage and use. Moreover, concerns from regulatory bodies such as FDA have prompted manufacturers to implement quality-by-design principles, where thorough characterization of all material components in the manufacturing process is preferred (2).
Often a drug product will require multiple excipients to obtain optimal stability, quality, and efficacy. In each case, the excipient must be tested for drug-excipient interactions that may potentially alter the drug and excipient functionality. In addition, formulation of challenging molecules such as complex small molecules, macromolecules, and peptides may not be achieved with conventional stabilizing excipients such as sugars, amino acids, and detergents (SADs). It is therefore crucial that excipient manufacturers work closely with the formulators and provide full characterization and understanding of excipients to be used in a drug formulation (1, 3). This article describes a recombinant human albumin (rAlbumin), as an example of a fully characterized multifunctional excipient for the formulation of protein therapeutics and explores its ability to prevent or minimize physical and chemical degradation of drug substances in various test formulations.