Breaking Barriers: Enhancing The Bioavailability Of Orally Delivered TPDs

By Rebecca Coutts Ph.D., Senior Director Pharmaceutical Development

Targeted protein degraders (TPDs), including PROTACs and molecular glues, represent a rapidly growing frontier in oral pharmaceuticals, offering an elegant way to eliminate, rather than just inhibit, disease-causing proteins. Although TPDs show immense therapeutic potential, their large, bulky structure often leads to poor solubility and limited permeability across intestinal membranes. This challenge results in low patient bioavailability, creating a delivery barrier for these highly effective therapeutics.

Fortunately, advanced drug delivery strategies are available to overcome the "brick dust" nature of TPDs. Enabling technologies like spray drying and hot melt extrusion transform TPDs into more soluble amorphous forms, while nanomilling dramatically increases the surface area for dissolution. The optimal path to market relies on strategic partnerships across the pharmaceutical supply chain, allowing for the combination of deep manufacturing expertise with cutting-edge formulation technologies. By establishing the CDMO as the single point of contact, product development becomes more efficient, bridging the gap between discovery and accessible treatments.

Learn more about the technologies and collaborative models accelerating TPD commercialization.