ABSTRACT
INTRODUCTION Physical and chemical properties of an active pharmaceutical ingredient that affect the performance of solid oral dosage forms, such as chemical stability, mechanical properties, hygroscopicity, solubility and dissolution rate, are strongly infl uenced by the solid-state form of the drug substance. Since drug product performance can only be assured when a drug compound is delivered in a consistent manner to the patient, pharmaceutical solids must be both chemically and physically stable. Chemical stability is the resistance to chemical reactions, which give rise to covalent bond changes (i.e., breaking or forming) under conditions relating to humidity, temperature, and photoirradiation, while physical stability refers specifi cally to the stability of a solid form with respect to polymorph transformations, hydration or dehydration, salt disproportionation, crystallization, or amorphization. Solid form (salt and polymorph) screening to identify chemically and physically stable forms of a drug substance is an essential fi rst step in pharmaceutical research and development. There are a number of excellent monographs, which independently cover aspects of salt and polymorph screening ( 1 – 3 ). The types of chemical reactions and physical transformations observed in bulk drug substances and formulations have also been thoroughly reviewed ( 4 , 5 ). The purpose of this chapter is to discuss the role of solid form screening and selection in ensuring the physicochemical stability of pharmaceuticals as drug substances and in solid oral drug products throughout their shelf life. Here, salt and polymorph screening are treated collectively as a key component of the product design. Although emphasis is clearly placed on identifying suitable crystalline forms of drug substances, the implications of amorphous forms introduced either by design or accident to ensure chemical and physical stability are also discussed.
