Drug solubility prediction

I J 7 Challenge of Drug SolubilitY Prediction and as H-bond interactions ... 

The rms deviation of this COSMO-RS drug-solubility prediction is 0.66 log-units on the training set. Considering the fact that the available data sets for aqueous drug solubility typically have an intrinsic experimented error of about 0.5 log-units (rms), this... 

The partition coefficient and aqueous solubility are properties important for the study of the adsorption, distribution, metabolism, excretion, and toxicity (ADME-Tox) of drugs. The prediction of the ADME-Tox properties of drug candidates has recently attracted much interest because these properties account for the failure of about 60 % of all drug candidates in the clinical phases. The prediction of these properties in an early phase of the drug development process could therefore lead to significant savings in research and development costs. 

Bergstrom, C. A. S. Computational models to predict aqueous drug solubility, permeability and intestinal absorption. Exp. Opin. Drug Metab. Toxicol. 2005, 1, 513-527. 

Bergstrom, C. A. S. D., Norinder, U., Luthman, K., Artursson, P. Experimental and computational screening models for prediction of aqueous drug solubility. Pharm. Res. 2002, 19,182-188. 

Delaney [4,14] and Klamt [16] argued that for drug-like compound datasets only about 20% of the variance of log S arises from AG s. This is further confirmed by the study of Wassvik et al. [15] in which 77% of the variance is due to the solubility of the supercooled liquid. Hence, applying crude estimates by mean values or by QSAR approaches we can reasonably expect that the inaccuracies introduced in dmg solubility prediction by our theoretical ignorance of AG s is less than, or at least not much bigger than, the inaccuracies introduced by the estimates of the larger park i.e. the liquid solubility, and by the experimental difficulties in solubility measurement. 

Jorgensen, W. L., Duffy, E. M. Prediction of drug solubility from structure. 

Jorgensen, W. L., Duffy, E. M. Prediction of drug solubility from Monte Carlo simulations. Eioorg. Med. Chem. Lett. 2000, 10, 1155-1158. 

It is advantageous with a new drug substance to be able to estimate what its solubility will be prior to carrying out dissolution experiments. There are several systems of solubility prediction, most notably those published by Amidon and Yalkowsky [14-16] in the 1970s. Their equation for solubility of p-aminobenzo-ates in polar and mixed solvents is a simplified two-dimensional analog of the Scatchard-Hildebrand equation and is based on the product of the interfacial tension and the molecular surface area of the hydrocarbon portion of a molecule. 

Huuskonen, J., Salo, M., Taskinen, J., Aqueous solubility prediction of drugs based on molecular topology and neural network modeling, J. 

USING THE STRUCTURE OF A DRUG TO PREDICT PROPERTIES SUCH AS WATER SOLUBILITY... 

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