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Exploring the Physical Form Landscape of Clozapine, Amoxapine and Loxapine

  • Rajni M. BhardwajEmail author
Chapter
Part of the Springer Theses book series (Springer Theses)

Abstract

This chapter highlights the value of combined experimental and computational approaches in describing the effect of small changes in molecular structures on solid-state structure and overall extent of solid-state diversity. Experimental solid form screening for an atypical antipsychotic agent clozapine yielded four novel physical forms including monohydrate, two crystalline solvates and an amorphous phase. The crystal energy landscape confirmed that there are no alternative packing arrangements which are thermodynamically competitive with an only experimentally obtained anhydrous form. Crystal structure prediction studies provided an explanation for different solid-state diversity of olanzapine (60 solid forms) as compared to clozapine (4 solid forms) as well as presence/absence of centrosymmetric dimer in the crystal structures of olanzapine and clozapine polymorphs respectively. Another set of molecules differing in one methyl group i.e. an anti-depressant agent amoxapine and a tranquiliser agent loxapine exhibited monomorphism and polymorphism respectively. Crystal structure prediction studies and packing efficiency calculations revealed that the methyl group in loxapine is playing a significant role in increasing the range of accessible solid forms.

Keywords

Succinic Acid Lower Energy Structure Piperazine Ring Molecular Pair Intermolecular Interaction Energy 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  1. 1.Lilly Corporate CenterEli Lilly and CompanyIndianapolisUSA

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