TY  - JOUR
T1  - Poorly Soluble Phytochemicals Change Rank After Formulation: A Developability Model Connecting Solid State, Dissolution, Biorelevant Exposure, and Delivery-Strategy Selection
A1  - Ahmed Ben Ali
A1  - Samira Gharbi
A1  - Nabil Jebali
JF  - Specialty Journal of Pharmacognosy, Phytochemistry, and Biotechnology
JO  - Spec J Pharmacogn Phytochem Biotechnol
SN  - 3062-441X
Y1  - 2025
VL  - 5
IS  - 2
DO  - 10.51847/AnCkYJkw7T
SP  - 32
EP  - 42
N2  - Poor aqueous solubility frequently lowers the apparent developability of phytochemical candidates, yet that judgment is often made before formulation has revealed whether the limitation is intrinsic, state-dependent, or technologically tractable. This article develops an original formulation-aware developability model in which candidate quality is treated as conditional on material state, gastrointestinal dissolution behavior, exposure-relevant solution state, and the suitability of the selected delivery strategy. Evidence from formulated phytochemicals and mechanistic pharmaceutics shows that formulation can alter oral exposure, but also that increased apparent solubility does not necessarily translate into greater absorption. Solid-state conversion, supersaturation, precipitation, colloidal association, thermodynamic activity, permeability, digestion, and presystemic handling may reinforce or oppose one another. The proposed model therefore distinguishes native-state deficit, formulation leverage, residual developability liabilities, and confidence in translation rather than ranking candidates solely by equilibrium solubility or an isolated dissolution endpoint. Biorelevant testing is positioned as an interpretive bridge between material properties and exposure, with physiological buffer conditions, transfer behavior, colloidal states, and absorption-relevant sinks determining what a dissolution result can legitimately imply. Rank reversal is consequently treated as a testable change in relative candidate priority after strategy-conditioned evaluation, not as evidence that formulation universally rescues poor compounds. The framework is intended for comparative prioritization and hypothesis generation. It remains nonvalidated prospectively, depends on compound-specific evidence, and requires external testing across chemically diverse phytochemicals, formulation classes, and progressively more physiologically informative experimental systems.
UR  - https://galaxypub.co/article/poorly-soluble-phytochemicals-change-rank-after-formulation-a-developability-model-connecting-solid-fivwceltp3mvgiu
ER  -