Christopher Lipinski - Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings.

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      Publication Details (including relevant citation   information): Lipinski, C. A., Lombardo, F., Dominy, B.   W., Feeney, P. J., Advanced drug delivery reviews,   2001, 46 (1-3), pp 3-26

      Abstract: Experimental and computational   approaches to estimate solubility and permeability in discovery   and development settings are described. In the discovery setting   'the rule of 5' predicts that poor absorption or permeation is   more likely when there are more than 5 H-bond donors, 10 H-bond   acceptors, the molecular weight (MWT) is greater than 500 and the   calculated Log P (CLogP) is greater than 5 (or MlogP > 4.15).   Computational methodology for the rule-based Moriguchi Log P   (MLogP) calculation is described. Turbidimetric solubility   measurement is described and applied to known drugs. High   throughput screening (HTS) leads tend to have higher MWT and Log   P and lower turbidimetric solubility than leads in the pre-HTS   era. In the development setting, solubility calculations focus on   exact value prediction and are difficult because of polymorphism.   Recent work on linear free energy relationships and Log P   approaches are critically reviewed. Useful predictions are   possible in closely related analog series when coupled with   experimental thermodynamic solubility measurements.

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