Thermodynamic Approaches to the Challenges of Solubility in Drug Discovery and Development

This paper considers fundamental aspects determining the processes of drug compound dissolution and distribution in solvents/systems modeling biological media. Special attention is paid to the complex analysis of thermodynamic functions of sublimation and solvation/hydration processes during structural modification of lead/hit compounds and their influence on dissolution processes. The paper shows that at the first stages of drug design it is necessary to develop algorithms of optimizing the properties determining absorption, distribution, metabolism, and excretion (ADME) characteristics of molecules: in particular, diffusion flux density through lipophilic membranes. Using sulfonamides and nonsteroidal anti-inflammatory drugs (NSAIDs) as an example, we have demonstrated the efficiency of approaches to manipulating thermodynamic functions of the basic processes that result from delivering compounds to the points of their operation. We have formulated several criteria of compound selection for further tests.