Drug solubility potential effects

Caco-2 cells have been valuable in the estimation of drug absorption potential, transport mechanisms, and effect of permeation enhancers on transepithelial transport.35,39,53,67-69,78-81 Owing to the sensitivity of the cells and the limited solubility of new molecular entities, Caco-2 permeability studies are routinely done with relatively low concentration of compounds. One way to increase the solubility of these compounds is to use organic solvents. The low tolerability of Caco-2 cells to organic solvents limits the use of this approach in permeability studies. 

When cosolvents are used to enhance solubility, the potential effects on drug stability must be remembered. The benefit of the enhanced solubility must be weighed against potentially undesirable effects on drug stability. 

Solubility issues are universal for activity and property screening, both HTS and traditional bench-top assays. It significantly impairs the quality of biological assays, ADME/TOX screens and in vivo activity measurements. This chapter focuses on solubility issues and potential solutions for screening assays in early drug discovery. The effects of solubility on absorption and oral bio availability will be addressed elsewhere in this book. 

Cartlidge SA, Duncan R, Lloyd JB, Kopeckova-Rejmanova P, Kopecek J. Soluble, crosslinked N-(2-hydroxypropyl)-methacrylamide copolymers as potential drug carriers. 2. Effect of molecular weight on blood clearance and body distribution in the rat after intraveneous administration. Distribution of unfractionated copolymer after intraperitoneal, subcutaneous or oral administration. J Cont Rel 1987 4 253-264. 

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