Befetupitant

Poor aqueous solubility and slow dissolution rate of active pharmaceutical ingredients (APIs) are often encountered challenges during oral drug development, leading to variable and insufficient bioavailability. To overcome these challenges, a so-called "enabling" formulation strategy is often pursued. Among these, amorphous solid dispersions (ASDs) are established as an effective means of improving drug absorption. However, evaluating the outcome of in vitro ASD screening approaches and relating this to the expected bioavailability increase can be difficult if not done systematically. Here we show, for the first time, how the combination of a high-throughput ASD screening method with the refined Developability Classification System (rDCS) can streamline the formulation of poorly soluble APIs as ASDs. Using the Screening of Polymers for Amorphous Drug Stabilization (SPADS) approach to rapidly prepare ASD films, the improvement in dissolution performance of three APIs (befetupitant, celecoxib and itraconazole) was investigated with eight polymeric carriers. The results showed that the concentration of dissolved API was highly dependent on both the carrier and the drug load. For the APIs studied, Eudragit E, HPMC 100LV and Soluplus showed especially advantageous effects as carriers. Translating these results into the rDCS framework allowed for the visualization of the left-shift (more favorable for absorption) in classification. Several ASD films were classified as rDCS class I, showing a major improvement from the initial IIb classification of the pure API. This novel approach could be expanded to include a diverse set of screening methods for enabling formulation strategies, where the rDCS can allow for a direct comparison and support formulation selection.