Impact of Solid-State Characteristics to the Physical Stability of Drug Substance and Drug Product

Abstract

In the drug development and commercialization process, the acceptable stability of the drug substance and drug product is one of the basic requirements for clinical studies, regulatory approval, and marketing. The stability of a drug product is related not only to the intrinsic chemical stability of the drug molecule, but also to the physical forms, manufacturing processes, interactions among formulation components, container closure systems, and storage conditions. In the past two decades, there has been a significant increase in the mechanistic understanding of the solid-state characteristics of pharmaceutical systems, along with the advancement of analytical techniques. Physical stability, as one of the quality attributes of drug products, should be designed into the formulation components and critical manufacturing steps using the Quality by Design (QbD) strategy to achieve intended shelf-life and product performance. In this Chapter, the major physical stability attributes of drug dosage forms are discussed with focus on the effects of solid-state properties of drug substance and manufacturing processes. The solid-state physical changes involving polymorphs, hydrates, amorphous forms, and the effect of water are highlighted.