TY  - JOUR
T1  - Designing within the Excipient–Process–Patient Triangle to Anticipate Formulation Failure before Clinical and Manufacturing Translation
A1  - Ana Rodrigues
A1  - Tiago Martins
A1  - Bruno Lopes
JF  - International Journal of Pharmaceutical Research and Allied Sciences
JO  - Int J Pharm Res Allied Sci
SN  - 2277-3657
Y1  - 2025
VL  - 14
IS  - 2
DO  - 10.51847/Vt0OFej0FS
SP  - 56
EP  - 65
N2  - Pharmaceutical formulation failure is often investigated through separate assessments of composition, manufacturing process, stability, product performance, or patient use. This fragmented approach can overlook failures that arise only when an excipient attribute encounters a particular process exposure and the resulting dosage form is used under physiologically or behaviourally variable conditions. This article develops an original, non-empirical formulation-risk architecture organized around an Excipient–Process–Patient Triangle. The architecture distinguishes three interacting domains: excipient functionality, variability, compatibility, and impurity burden; process exposures capable of transforming material and product attributes; and patient physiology, behaviour, capability, and administration conditions. It proposes that formulation performance should be evaluated at the intersection of these domains rather than inferred from isolated compliance with material specifications, nominal process settings, or standard laboratory tests. Interaction-driven failure scenarios include latent incompatibility, process-activated instability, loss of release-controlling structures, physiology-revealed excipient effects, administration-induced performance shifts, and three-way translation mismatches. Early warning indicators are organized around unexplained material sensitivity, process-dependent state change, representative-use dependence, analytical discordance, and extrapolation beyond the evidence domain. Corresponding decision gates distinguish proceeding, conditional progression, targeted stress testing, reformulation or process redesign, evidence escalation, and suspension of translation. Validation would require controlled perturbation of excipient, process, and patient-relevant variables; orthogonal characterization; external-condition testing; manufacturing-scale evaluation; and representative-use studies. The proposed architecture is intended to structure risk recognition and evidence planning. It does not establish predictive accuracy, clinical superiority, regulatory acceptability, universal applicability, or readiness for routine deployment.
UR  - https://ijpras.com/article/designing-within-the-excipientprocesspatient-triangle-to-anticipate-formulation-failure-before-cli-yrvdbolqawz96m1
ER  -