- Reframes formulation development from maximising mean bioavailability to designing exposure robustness across physiological variability of the intended patient population.
- Integrates biopredictive dissolution, physiologically based biopharmaceutics modelling and model-informed drug development to predict clinical exposure pre-first-in-human.
- Aims to prevent post-FIH liabilities such as food effects, pH sensitivity and drug-drug interactions, enabling predictable, clinically translatable oral products.
Drug Discov Today. 2026 Aug 31:104791. doi: 10.1016/j.drudis.2026.104791. Online ahead of print.
ABSTRACT
Oral drug product development has traditionally been optimized around maximizing mean bioavailability in healthy volunteers, yet clinically relevant exposure liabilities including food effects, pH sensitivity, transit dependence and drug-drug interactions often emerge only after first-in-human (FIH) studies, driving label restrictions or reformulation. We introduce Exposure Robustness by Design (ERbD) – a prospective framework that reframes formulation development from maximizing mean bioavailability toward achieving exposure robustness across the physiological variability of the intended patient population. Supported by biopredictive dissolution, physiologically based biopharmaceutics modeling and model-informed drug development, ERbD guides pre-FIH formulation decisions to support predictable, clinically translatable oral drug products.
PMID:42674208 | DOI:10.1016/j.drudis.2026.104791
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