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