Palatability-by-Design for Oral Drug Products: A Unified Framework for Evaluation and Optimization.

Palatability is a critical determinant of acceptability and adherence for oral drug products, especially in pediatric and geriatric populations, yet its evaluation remains fragmented across dosage forms and often disconnected from formulation-development decisions. In this review, we propose Palatability-by-Design (PbD) as a unified framework that treats palatability not as a loosely defined sensory outcome, but as a development variable with identifiable failure modes, measurable sensory critical quality attributes (CQAs), and controllable formulation/process levers. We first define a two-dimensional framework comprising swallowability (oral physical comfort) and palatability (sensory appreciation), and then outline major sensory failure modes that are relevant to oral drug development. Next, we compare subjective and objective evaluation methods using a fit-for-purpose logic, emphasizing decision relevance, surrogate calibration, and the need to anchor instrumental readouts to perception-relevant endpoints. We further integrate these elements into a PbD workflow that links sensory CQAs to risk assessment, formulation/process variables, acceptance criteria, and verification. Finally, we summarize failure-mode-guided optimization strategies, including taste masking and dosage-form modification, and discuss future needs for data standardization, translational calibration, and patient-centred implementation. By aligning sensory science with pharmaceutical quality and control logic, PbD provides a more practical basis for rational, patient-focused oral product development.