Development and Validation of High-Throughput Crystallisation and Analysis (HTCAA) Methodology for Physical Form Screening

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


High throughput crystallisation methodology for physical form screening using multi-well plate and Raman microscopy was developed and validated. This methodology offers various advantages including small sample requirement (~1 mg per crystallization), no sample preparation, rapid data acquisition using non-destructive analytical technique and rapid data analysis using chemometric techniques. The effectiveness of this methodology was assessed by applying it to three pharmaceutical molecules i.e. olanzapine, clozapine and amoxapine. Sixteen novel solid forms of olanzapine,  3 novel physical forms of clozapine and 10 novel salts of amoxapine were obtained by utilising a total of only ~640 mgs of API and ~65 ml of solvents. The developed methodology is an effective tool for preliminary investigation of solid-form diversity during early stages of drug development and provides data to guide further crystallization efforts in appropriate direction.


Raman Spectrum Physical Form Fume Hood Raman Shift Polarise Light Microscopy 
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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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