Discovery Formulations: Approaches and Practices in Early Preclinical Development

Technological innovations in biology, chemistry, and medicine have provided the pharmaceutical industry a wealth of targets and molecules with the potential to treat diseases once thought intractable to drug therapy. These advances have brought about a renaissance in the industry and current estimates suggest there are more than 5,000 potential new medicines in human testing, a high percentage of which would be considered “first in class” (Long and Works 2013). It has been suggested that pharmaceutical portfolios have shifted from commercially crowded therapeutic areas where the probability of approval is high to less crowded areas with novel targets and subsequent lower approval rates (Scannell et al. 2012). Additionally, there is a growing recognition that modulation of multiple targets (e.g., magic shotguns) rather than a single target (e.g., magic bullet) by a drug may provide greater therapeutic benefit to the patient (Roth et al. 2004; Morphy 2010; Gleeson et al. 2011). These transformations have resulted in a decline in new drug approvals and more importantly, a gradual but significant shift out of conventional druggable chemical space (Pammolli et al. 2011). The consequential increase in complexity, both in terms of the molecules and their biological targets, combined with the increasing need to work in an efficient and cost-constrained environment has necessitated an evolution in the role of pharmaceutical sciences in discovery support. Traditionally, the pharmaceutical scientist participated on discovery teams only in the later phases of lead development or in the lead optimization phase, and their role was largely to assess the development risks (developability) of the molecule advancing to clinical dosing (Venkatesh and Lipper 2000). These activities, while