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.
Josh Marsh is a member of the Advanced Drug Delivery Technologies team at Lonza’s site in Bend, Oregon, USA. He started his career at the Bend site in 2016. Josh has focused on the design of amorphous solid dispersion formulations and informative dissolution testing with the goal of improving bioavailability. He is passionate about using PBBM modeling to further the understanding of in vivo drug absorption, and the design of better drug products for clients and patients. Josh earned his B.S. in Chemistry from Oregon State University.
Abhijeet Sinha is the Manager of Solid Form Services at Lonza’s site in Bend, Oregon, USA, where he works on product development and internal R&D in preformulation, polymorph, salt and co-crystal screens. Abhijeet joined Lonza in 2020 from Kansas State University’s Chemistry Department, where he served as a Senior Scientist and Director of the university’s x-ray crystallography facility. Abhijeet’s expertise includes molecular modeling, in silico screening of active pharmaceutical ingredients (APIs) and polymorphs, particle engineering, industrial crystallization, organic and inorganic chemistry, and x-ray crystallography. He earned his B.Sc. and M.Sc. degrees in Chemistry at Delhi University, and received a Ph.D. in Inorganic Chemistry from Kansas State University. After graduation, Abhijeet completed two years of postdoctoral work at University College Cork, mapping the solid-form landscape of APIs for the pharmaceutical industry.
