Stability of Drugs and Dosage Forms Sumie Yoshioka

Chapter 1
Introduction
In this book, we define “pharmaceuticals” as drug substances having pharmacological
effects and the dosage forms containing these drug substances, which are intended for
therapeutic use. Drug substances used at the present time range from small-molecular-weight
chemicals to polymers such as proteins. In the future, products derived from genomic
research will have to be included. Some drug substances are susceptible to chemical
degradation under various conditions owing to their fragility of their molecular structure.
Other drug substances undergo physical degradation changes rather than chemical degradation,
leading to various changes in their physical state.
Chemical degradation and physical degradation of drug substances may change their
pharmacological effects, resulting in altered efficacy therapeutic as well as toxicological
consequences. Because pharmaceuticals are used therapeutically based on their efficacy and
safety, they should be stable and maintain their quality until the time of usage or until their
expiration date. The quality should be maintained under the various conditions that pharmaceuticals
encounter, during production, storage in warehouses, transportation, and storage
in hospital and community pharmacies, as well as in the home. Therefore, understanding the
factors that alter the stability of pharmaceuticals and identifying ways to guarantee their
stability are critical.
Since the early 1950s, many studies on the stability of pharmaceuticals, degradation
pathways, rates of reaction, and the means of stabilizing drugs have been well documented
in the primary literature. Ongoing studies, especially those with complex new drugs such as
proteins, are continuously adding to our knowledge base. New assay methodologies are
being developed, and new ways of treating stability data are also evolving. This is especially
the case with the newer complex drugs and dosage forms.
This book examines the stability of pharmaceuticals. In Chapters 2 and 3, the chemical
and the physical stability of drug substances are described. In each of these chapters,
degradation pathways, probable mechanisms, factors affecting stability, methods of stabilization,
and prediction methodologies are discussed. Chapter 4 describes the physical and
chemical stability of drugs in complex, heterogeneous dosage forms containing both the
drug and excipients. Here, both prefomulation stability studies and those performed on the
final dosage form, including the effect that packaging might have on the stability, are
evaluated. Chapter 5 covers the rapidly changing area of protein and peptide pharmaceuticals.
The physical and chemical stability of these newer biotechnology products is often
difficult to characterize. Therefore, a range of methodologies is needed. The final chapter
concerns regulatory requirements for stability testing.
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