Rapid and cost-effective development of early-phase drug candidates is important in progressing molecules to first-in-human (FIH) trials. A common challenge is that many new chemical entities (NCEs) suffer from poor bioavailability because of their low aqueous solubility. For these molecules, it is critical to quickly screen for a lead enabled form, looking at both crystalline and amorphous alternatives, without adversely impacting pre-clinical and clinical study timelines and costs.

Physiologically based biopharmaceutics modeling (PBBM) software, such as the GastroPlus® platform from Simulations Plus, simulates the interplay of the physio-chemical, metabolism, and excretion properties of a molecule in conjunction with the target physiology and formulation attributes. When coupled with targeted strategic in vitro measurements, PBBM modeling can be used in the early stages of drug development to identify risks to absorption, and evaluate the ability of enabled forms and formulations to overcome these risks. Significant savings in time and effort are realized by eliminating the unnecessary in vitro and in vivo testing of suboptimal formulations. Furthermore, PBBM modeling informs and aids the design of preclinical and clinical studies with respect to dose, prandial state, drug-drug interactions (DDI), or gastric pH modification to maximize the likelihood of achieving desired PK profiles.

In this webinar, we will discuss the role of solid form screening and PBBM modeling to enable the accelerated timelines that are desirable in early-phase drug development. We will also share formulation maps for amorphous solid dispersions (ASDs) and the key criteria for salt screening that are used to select the optimal formulation in early-phase screening for enabled forms. Using a model drug case study, the optimized pathway to lead-enabled form selection using a combination of in vitro characterization techniques and in silico modeling tools will be highlighted.