Document Detail

Development of a high throughput equilibrium solubility assay using miniaturized shake-flask method in early drug discovery.
MedLine Citation:
PMID:  17722003     Owner:  NLM     Status:  MEDLINE    
Increasingly, pharmaceutical and biotech companies have begun to realize the importance of obtaining solubility information in early drug discovery as it is one of the critical parameters for lead selection and optimization. This report introduces a high-throughput equilibrium solubility (HT-Eq sol) assay using a novel miniaturized shake-flask approach and streamlined HPLC analysis. The new HT-Eq sol assay, validated and optimized via a test set of 85 marketed drugs and Novartis internal compounds, shows an excellent correlation to the conventional shake-flask thermodynamic solubility data generated in-house and the equilibrium solubility results reported in literature. It therefore offers a fast, reliable and cost-effective screening tool for solubility assessment in early drug discovery, allowing for prioritization of drug candidates using aqueous solubility in conjunction with other profiling information and efficacy data. Our work demonstrates that presence of a small amount of DMSO (0.5-5%) will result in significant overstimation of equilibrium solubility (up to 6 folds). In addition, monitoring of drug dissolution process using the current approach as well as the interplay between equilibrium solubility data and those from kinetic solubility are discussed.
Liping Zhou; Linhong Yang; Suzanne Tilton; Jianling Wang
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of pharmaceutical sciences     Volume:  96     ISSN:  0022-3549     ISO Abbreviation:  J Pharm Sci     Publication Date:  2007 Nov 
Date Detail:
Created Date:  2007-11-05     Completed Date:  2007-12-11     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2985195R     Medline TA:  J Pharm Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3052-71     Citation Subset:  IM    
Copyright Information:
Copyright 2007 Wiley-Liss, Inc.
PreClinical Profiling, Novartis Institutes for BioMedical Research, 250 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA.
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MeSH Terms
Chromatography, High Pressure Liquid
Combinatorial Chemistry Techniques / methods
Dimethyl Sulfoxide / chemistry
Microchemistry / methods
Pharmaceutical Preparations / chemistry*
Reg. No./Substance:
0/Pharmaceutical Preparations; 67-68-5/Dimethyl Sulfoxide

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