Chapter 12 - Preformulation Studies of Drug Substances, Protein, and Peptides: Role in Drug Discovery and Pharmaceutical Product Development

Abstract

Preformulation studies focus on the concepts of physicochemical properties which are vital for any new drug molecule and/or proteins/peptides. These properties not only affect their therapeutic efficacy but also the development process of their specific dosage form. The preformulation of peptides and proteins is complicated as compared to synthetic drug molecules. Owing to their complex structural architecture, the formulation of peptides and proteins is hindered by two important factors, i.e., stability and absorption. The structure of peptide or proteins has multiple sites which are susceptible to various physical instability (e.g., denaturation, precipitation) as well as chemical instability (e.g., oxidation, deamidation, beta-elimination). Besides, different types of approaches are required for their delivery across the gastrointestinal tract. In particular, for oral administration, it is imperative to design the dosage form in such a way that it is not only able to initially stabilize the drug but also to protect it from the extreme acidic environment of the stomach as well as circumvent the enzymatic degradation of the drug in the gastrointestinal tract. The recent developments in the domain of peptides and proteins have paved the way for innovative drug discovery and the design of novel delivery systems in order to develop potential therapies both for the present and future. The current chapter discusses the various physicochemical properties of drug substances including peptides and proteins while emphasizing the influence of preformulation studies in the design, development, and delivery of such drugs and peptidomimetics.