Solubility drug discovery

Lipinski, C., Lombardo, F., Dominy, B., and Feeney, P. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv. Drug. Deliv. Rev. 23 3—25. 

Lipinski, C.A., Lombardo, F., Dominey, B.W., Feeney, P.J. (1997) Experimental and Computational Approaches to Estimate Solubility and Permeability in Drug Discovery and Development Settings. Advances in Drug Delivery Review, 46, 3-26. 

Liu, R., So, S.-S. Development of quantitative structure-property relationship models for early ADME evaluation in drug discovery. 1. Aqueous solubility./. Chem. Inf. Comp. Set. 2001, 41, 1633-1639. 

This chapter is written for a medicinal chemistry audience. The focus is on the importance of drug solubility in water and in dimethylsulfoxide (DMSO) in the types of activities likely to be of interest to medicinal chemists. The emphasis is on the discovery stage as opposed to the development stage. The reader will find numerous generalizations and rules of thumb relating to solubility in a drug discovery setting. 

Aqueous solubility is not usually considered a priori as a problem in the drug discovery of acidic compounds. More important issues are (i) the high serum albumin binding of stronger acids, (ii) the very low or nonexistent central nervous system penetration of stronger acids, (iii) the low volumes of distribution of acids limiting these mostly to plasma compartment targets, (iv) the possibility of formation of... 

Since most drug discovery projects deal with very sparingly soluble compounds, the usual CE sample concentration would lead to precipitation. The handling of real dmg candidate molecules is poorly developed in CE applications, in comparison to the most robust potentiometric method. 

Therefore, the final equation is relatively simple despite the fact that the derivation is complex. Equation (145) shows that the intrinsic dissolution rate depends on the diffusion coefficient and solubility of the drug, disk rotational speed, and the viscosity of the dissolution medium. The amount of drug dissolving per unit area is the same everywhere on the disk s surface. This makes the disk a powerful experimental tool in drug discovery and development. 

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