A Comprehensive Approach for Solid Form Selection in Preclinical Development and Beyond.

Different solid forms (polymorphs, salts, cocrystals) of an active pharmaceutical ingredient (API) can have very different physico-chemical properties. Those differences can impact bioavailability, solubility, dissolution rate, side effect incidence, stability, API and drug product manufacturability, and other important parameters. Most APIs can exist in multiple solid forms, including polymorphs, hydrates, solvates, salts, cocrystals, and non-crystalline forms. The goal in screening and selection is to produce an optimal solid form based on parameters such as crystallinity, stability, solubility, hygroscopicity, and ease of production ("manufacturability"). Understanding the process chemistry is paramount for reproducibility during drug development and manufacturing. Here we discuss various solid forms and a comprehensive way to approach solid form screening for regulatory, manufacturing, financial, and intellectual property needs.
Keywords: Polymorphism, pharmaceutical salt, pharmaceutical cocrystal, amorphous materials, solid-state intellectual property.