Compound solubility is one of the key physicochemical properties that is essential to optimise for drug formulation and systemic absorption. While there are several kinetic and thermodynamic solubility assays that can be incorporated into the compound optimisation cascade, it is also useful to employ theoretical calculations for very high-throughput predictions of aqueous solubility. The general solubility equation (GSE), first introduced in the 1980s and later optimised in the early 2000s, uses only 2 parameters (the Celsius melting point and octanol-water partition coefficient) and has been a standard within the pharmaceutical industry. This validation paper from 2001 compares the use of the GSE with a Monte Carlo simulation method on 150 compounds and determines that, on average, the GSE provides solubility predictions closer to experimental values. Considering the speed at which the GSE can be applied compared to Monte Carlo simulations, this highlights the usefulness of the simple equation for guiding compound design.
Prediction of Drug Solubility by the General Solubility Equation (GSE).
Chem. Inf. Comput. Sci. 2001, 41, 2, 354–357
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