The General Solubility Equation (GSE) provides a simple method of estimating the molar aqueous solubility of an organic non-electrolyte in water (S w ) as a function of its celsius melting point (MP) and octanol-water partition coefficient (K ow ):The melting term of the GSE is based upon the ClausiusClapyron equation and Waldens rule. The aqueous activity coefficient is assumed to be the reciprocal of the octanol-water partition coefficient. The constant is based upon the molarity of pure octanol. There are no fitted parameters in the GSE. Extension of the GSE to weak electrolytes in buffered aqueous solutions is straightforward. The concentration of the ionized species, S i , is accounted for by incorporating one additional term, which contains the pK a of the solute and pH of the solution. For a weak acid, S total S w S i S w [1 10The solubility of a weak electrolyte in unbuffered water requires further consideration because the solute will determine the pH of the solution. It is shown that in unbuffered mediaThus, it is not necessary to explicitly know the pH of the saturated solution to estimate the solubility of a weak electrolyte in water. The GSE is validated on data set of over a thousand compounds, covering a wide range of structural categories. The GSE is compared to a number of other solubility estimation techniques using the criteria of accuracy of fit, applicability, parsimony, convenience, and elegance.

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The ability to predict the passive intestinal absorption of organic compounds can be a valuable tool in drug design. Although Lipinski's 'rule of 5' is commonly used for this purpose, it does not routinely give reliable results. An alternative 'rule of unity' is proposed to predict the absorption efficiency of orally administered drugs that are passively transported. The rule of unity based upon the theoretical principals that govern passive transport. The 'rule of 5' and the 'rule of unity' are compared using experimentally determined passive human intestinal absorption data for 155 drugs. Absorption values which are >50% of the dose are classified as well absorbed and absorption values which are

A model is proposed for the prediction of either high or low fraction absorbed for an orally administered, passively transported drug on the basis of a new absorption parameter, P. The model includes only two inputs: the octanol-water partition coefficient (K ow ) and the dimensionless oversaturation number (O Lumen ). The latter is the ratio of the concentration of drug delivered to the gastrointestinal (GI) fluid to the solubility of the drug in that environment. Thus, O Lumen is equal to the dose-normalized solubility for suspensions and unity for solutions. The value of P increases with an increase in K ow and a decrease in O Lumen for suspensions, and is equal to K ow for solutions. The effectiveness of the model is validated using experimental human gastrointestinal absorption data for 98 compounds. About 88% of these drugs are correctly predicted to be either well absorbed or poorly absorbed based solely upon whether their P value is greater than or less than unity. Thus, the use of a single absorption parameter, P provides a simple means to estimate whether or not an orally administered drug undergoing passive transport will be absorbed efficiently. The advantage of this parameter is that it is based upon simple, easily measured (or calculated) physical chemical data. It is especially noteworthy that experimental measurement of in vitro membrane transport is not required. The model based on the new absorption parameter is shown to have wider applicability than current available models for predicting the fraction absorbed.