Enabled Form Selection For Oral Drug Products Using A Combination Of In-Silico Modeling And In-Vitro Measurements

In the realm of early-phase drug development, the swift and cost-effective advancement of drug candidates to First-in-Human (FIH) trials is paramount. A frequent obstacle encountered is the low aqueous solubility of many New Chemical Entities (NCEs), which can significantly hinder bioavailability. To overcome this challenge, it is imperative to rapidly identify lead-enabled forms (crystalline or amorphous) without compromising preclinical and clinical timelines or costs.

Physiologically-based pharmacokinetic (PBPK) modeling, such as that offered by GastroPlus®, provides a powerful tool for simulating the intricate interplay of a molecule's physiochemical, metabolic, and excretion properties within the context of target physiology and formulation attributes. When integrated with targeted in vitro measurements, PBPK modeling empowers researchers to proactively identify potential absorption risks and evaluate the efficacy of enabled forms and formulations in addressing these challenges. By minimizing unnecessary in vitro and in vivo testing of suboptimal formulations, substantial time and resource savings can be realized. Moreover, PBPK modeling offers valuable insights for designing preclinical and clinical studies, enabling optimization of factors such as dose, prandial state, drug-drug interactions (DDIs), or gastric pH modification to achieve desired pharmacokinetic profiles.

This webinar explores the synergistic relationship between solid form screening and PBPK modeling in accelerating early-phase drug development. We delve into the intricacies of formulation maps for amorphous solid dispersions (ASDs) and the key criteria for salt screening, which are essential for selecting the most promising formulation in early-phase screening for enabled forms. A model drug case study illustrates how a strategic combination of in vitro characterization techniques and in silico modeling tools can streamline the pathway to lead-enabled form selection.

Key Learning Objectives:

• Gain a deep understanding of how PBPK modeling can proactively identify potential oral absorption risks for early drug candidates.
• Explore the pivotal role of solid form screening and form selection in optimizing oral pharmaceutical development.
• Discover how the synergistic application of PBPK modeling, in vitro testing, and solid form screening can guide the early selection of drug form and formulation to achieve preclinical and clinical study goals (e.g., bioavailability enhancement).