Nowadays, a large increase in CMC budgets and extended development time cycles are observed in small molecule projects. In the research phase, the drug molecule candidates are selected according to multi-criteria e.g. activity, selectivity, metabolism stability…and should be selected rationally according to “developability” criteria to expedite timeline, limit budget and avoid potential hurdles in the subsequent development phases. However, during drug candidate optimization phases, the low solubility has become one of the most frequent issues that prevent “formulability” into conventional dosage forms. Also, safety studies are usually problematical during of the preclinical derisking for clinical development with these limited solubility candidates.
This lecture describes, in a comprehensive mode, strategies to alleviate solubility deficits at the interface between drug research and development. Solubility criteria to apply on drug candidate will be detailed. Ambitious strategies on drug candidate and concrete case studies to improve “formulability” or derisk development issues will be described.