Preclinical Development – Chemical
2019 PharmSci 360
Amorphous solid dispersions (ASDs) are widely used as a formulation approach to increase the oral absorption of poorly soluble drugs. But to prove effective, ASD drug products must be designed to achieve the desired pharmacokinetic profile in vivo while balancing the complex interplay between dissolution, precipitation, and drug speciation in the gastrointestinal tract. With the use of advanced in vitro analytical tools and in silico absorption modeling, the dynamic dissolution behavior of ASDs can be well understood, providing key information about target bioperformance attributes for optimization of the final drug product. Understanding ASD formulation performance can help with robust predictions of drug performance in vivo when careful consideration is given to biorelevant in vitro test design as well as treatment of in vitro data in the absorption model for prediction.
Coupling in vitro/in silico tools to predict in vivo performance is demonstrated here for a BCS Class II compound, belinostat.