The pharmaceutical industry is increasingly focusing on the development of protein degraders, particularly Proteolysis Targeting Chimeras (PROTACs), as a novel therapeutic approach. These small molecules have shown great promise in targeting disease-causing proteins for degradation. However, their development faces significant formulation challenges, particularly in terms of permeability and bioavailability. This post delves into these challenges, and discusses how SeraNovo’s NanoGlass™ technology has significantly enhanced the bioavailability of these molecules.
The Challenge of Size and Permeability
The Challenge of Solubility
A poor aqueous solubility can also be a major contributor to inadequate bioavailability. Solubility-limited bioavailability is a product of the dose, permeability and aqueous solubility. In other words, the aqueous solubility is insufficient to dissolve the required dose during the absorptive window. As PROTACs are poorly permeable, the required aqueous solubility should be even higher when compared to permeable APIs (for the same dose). Unfortunately, PROTACs typically have solubility values in intestinal conditions of <10 µg/mL, albeit VHL-based or CRBN-based.
SeraNovo's NanoGlass™ Technology: A Game Changer
SeraNovo has effectively addressed the formulation challenges associated with PROTACs through its expertise in formulating highly crystalline, poorly soluble, and high melting point small molecules. We generate and stabilize amorphous nanoparticles in the GI Tract, maximizing solubility, dissolution, and absorption. We address critical formulation challenges including stability, manufacturability, and final dosage form. Additionally, we incorporate permeability-enhancers into these mixtures, offering a comprehensive solution to enhance the formulation of PROTACs and other protein degraders.
