Formulation-Driven Solubility Enhancement of PROTAC ARCC-4 through Acid-Incorporated Eudragit® EPO ASDs

Lukas Mild – doctoral student, Department of Pharmaceutics, University of Bonn, Germany; Christian Steinebach – professor, Department of Pharmaceutical/ Medicinal Chemistry, Institute of Pharmacy, University of Greifswald, Germany; Karl G. Wagner – professor, Department of Pharmaceutics, University of Bonn, Germany

Introduction:

Proteolysis targeting chimeras (PROTACs) induce the degradation of disease-relevant proteins of interest by recruiting E3 ligases. Besides being highly effective in vitro, many PROTACs exhibit poor aqueous solubility and limited bioavailability (1). Based on previous investigations, the model compound ARCC-4 was used. This VHL (von Hippel-Lindau)-based molecule degrades androgen receptors that may be overexpressed in certain types of prostate cancer (2). A ternary amorphous solid dispersion (ASD) formulation prepared by vacuum compression molding (VCM) was developed to improve its solubility.