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25th Croatian meeting of chemists and chemical engineers, Poreč, 2017.
The Potential of Computed Crystal Energy Landscapes to Aid Solid-Form
Development
Title in Croatian
(title may be maximum two lines)
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Susan M. Reutzel-Edens,1 Sarah L. Price2
1
Eli Lilly and Company, Indianapolis, IN USA
2
University College London, London, UK
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E-mail: [email protected]
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A key first step in developing a solid oral dosage form is to identify crystalline forms of the
drug molecule, generally through some form of crystallization screening. Crystallization
provides a means to purify and recover the drug substance coming out of the final step of
the synthesis and to isolate the drug in a crystalline form that is suitable for downstream
processing. It is also used to define the material properties (e.g., stability or solubility) of the
drug substance that will ensure consistency in the safety and efficacy profile of the drug
product throughout its shelf life. The ability of molecules to crystallize in many different
forms (including salts and co-crystals) creates opportunities to design properties into the
drug substance, but at the same time introduces challenges in deciding which form to
develop, selectively crystallizing the preferred form on a large scale, and establishing control
strategies around crystal form in the drug product. An ever-expanding range of techniques
has been shown capable of producing novel solid forms, yet it is possible that practically
important forms might not be found in the short timescales currently allowed for solid-form
screening. Here, we report on the state-of-the-art use of computed crystal energy
landscapes to complement pharmaceutical solid-form screening [1-2]. We illustrate how
crystal energy landscapes can help establish molecular-level understanding of the
crystallization behavior of APIs.
in silico solid form screen
molecule
solid form landscape
experimental solid form screen
Figure 1: Crystal structure prediction improves the effectiveness of experimental solid form screening.
References
[1] S.L. Price and S.M. Reutzel-Edens, Drug Discovery Today 21 (2016) 912-923.
[2] S.L. Price, D.E. Braun and S.M. Reutzel-Edens, Chemical Communications 52 (2016) 7065-7077.