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Int J Pharm. 2016 Sep 10;511(1):111-126. doi: 10.1016/j.ijpharm.2016.06.060. Epub 2016 Jun 24.

Novel high/low solubility classification methods for new molecular entities.

Author information

1
Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, State University of New York, Buffalo, NY, USA.
2
Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, State University of New York, Buffalo, NY, USA. Electronic address: memorris@buffalo.edu.

Abstract

This research describes a rapid solubility classification approach that could be used in the discovery and development of new molecular entities. Compounds (N=635) were divided into two groups based on information available in the literature: high solubility (BDDCS/BCS 1/3) and low solubility (BDDCS/BCS 2/4). We established decision rules for determining solubility classes using measured log solubility in molar units (MLogSM) or measured solubility (MSol) in mg/ml units. ROC curve analysis was applied to determine statistically significant threshold values of MSol and MLogSM. Results indicated that NMEs with MLogSM>-3.05 or MSol>0.30mg/mL will have ≥85% probability of being highly soluble and new molecular entities with MLogSM≤-3.05 or MSol≤0.30mg/mL will have ≥85% probability of being poorly soluble. When comparing solubility classification using the threshold values of MLogSM or MSol with BDDCS, we were able to correctly classify 85% of compounds. We also evaluated solubility classification of an independent set of 108 orally administered drugs using MSol (0.3mg/mL) and our method correctly classified 81% and 95% of compounds into high and low solubility classes, respectively. The high/low solubility classification using MLogSM or MSol is novel and independent of traditionally used dose number criteria.

KEYWORDS:

Analytical chemistry; Computational ADME; Computer aided drug design; High throughput technologies; In silico modeling; ROC curve analysis; Solubility

PMID:
27349790
PMCID:
PMC5003747
DOI:
10.1016/j.ijpharm.2016.06.060
[Indexed for MEDLINE]
Free PMC Article

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