Solid State Concerns During Drug Discovery and Development: Thermodynamic and Kinetic Aspects of Crystal Polymorphism and the Special Cases of Concomitant Polymorphs, Co-Crystals and Glasses
Daniel P. Otto,
Melgardt M. De Villiers.
During drug discovery and development the thermodynamics and kinetics
of crystal form transitions must be studied and the fundamental properties of
polymorphs must be identified. However, despite the accumulation of knowledge
and experimental evidence that support the understanding of crystallization, its
predictability still presents significant challenges. With the continuous development
of new drug delivery technologies, even more complex situations arise such as
difficult cases of polymorph selection, co-crystallization of different molecules, and
manipulation of the crystallization environment for example amorphous solids. This
review covers some fundamental thermodynamics and kinetics of simple system,
before the discussions consider at these special cases and how the manipulation of
thermodynamic and kinetic processes has increased our knowledge, understanding
and application of crystallization science during the drug development process.
Keywords: Thermodynamics, kinetics, crystallization, concomitant polymorphs, co-crystals, glasses.
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