At least some degree of solubility in water is necessary for active ingredients in pharmaceutical products to be effective in vivo. However, as efforts to discover and synthesise new active ingredients are pursued by industrial and academic medicinal chemists, achieving sufficient aqueous solubility can often be a significant limitation to clinical and commercial success…
Given the frequency and significance of this problem over the recent past, multiple solutions are being researched and applied in academia and industry.1 This review article provides a high-level description of the poor solubility problem and suggests a few techniques to deal with it.
The pharmaceutical discovery process can vary significantly depending on the characteristics of the intended target and therapeutic indication, availability of compounds with suitable properties to hit the target, and robustness of in vitro assays, among other differences. Irrespective of these differences, at some point in the discovery process the newly synthesised compounds will be dosed to animals to determine their pharmacological and toxicological activity in vivo. This is the point at which their aqueous solubility often becomes important. Occasionally, this realisation will occur during in vitro studies, but poor aqueous solubility is usually masked by the nature of these assays.
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