Solubility Enhanced Formulation Approaches to Overcome Oral Delivery Obstacles of PROTACs.

ABSTRACT: PROteolysis TArgeting Chimaeras (PROTACs) offer new opportunities in modern medicine by targeting proteins that are undruggable to classic inhibitors. However, due to their hydrophobic structure, PROTACs typically suffer from low solubility, and oral bioavailability remains challenging. At the same time, due to their investigative state, the drug supply is meager, leading to limited possibilities in terms of formulation development. Therefore, we investigated the solubility enhancement employing mini-scale formulations of amorphous solid dispersions (ASDs) and liquisolid formulations of the prototypic PROTAC ARCC-4. Based on preliminary supersaturation testing, HPMCAS (L Grade) and Eudragit^® L 100-55 (EL 100-55) were demonstrated to be suitable polymers for supersaturation stabi

SUBMITTER: Postges F 

PROVIDER: S-EPMC9863516 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature