%0 Journal Article
%T Can Formulation Rescue Orally Limited Phytochemicals? A Systematic Review of Bioavailability Gains, Exposure Evidence, and Translation Across Delivery Technologies
%A Olivia Bennett
%A Harry Collins
%A Jack Foster
%A Ethan Wright
%J Specialty Journal of Pharmacognosy, Phytochemistry, and Biotechnology
%@ 3062-441X
%D 2026
%V 6
%N 1
%R 10.51847/ZFFh0aBsCt
%P 142-152
%X Many phytochemicals combine pharmacological interest with low or variable oral systemic exposure arising from poor aqueous solubility, dissolution limitations, gastrointestinal instability, permeability constraints, efflux, and extensive presystemic metabolism. Formulation technologies are frequently presented as solutions, yet improvement in formulation performance is not equivalent to demonstrated improvement in systemic exposure, and exposure enhancement does not itself establish therapeutic benefit. A systematic-review framework was used to evaluate oral formulation studies according to measured pharmacokinetic exposure, formulation technology, comparator, analyte definition, evidence level, and translational setting. Human randomized or crossover pharmacokinetic evidence and preclinical oral pharmacokinetic studies were considered separately. Dissolution or permeability improvement without corresponding systemic-exposure evidence was not treated as proof of bioavailability rescue. Owing to substantial heterogeneity in compounds, formulations, doses, analytes, species, and comparators, synthesis was qualitative rather than quantitatively pooled. Repeated within-study increases in systemic exposure were reported across lipidic, self-emulsifying, nanoparticulate, supersaturating, cyclodextrin-based, gastroretentive, and hybrid delivery systems. Apparent gains were nevertheless conditional on compound properties, analytical definition, comparator selection, physiological setting, and evidence level. Human evidence was substantially narrower than the preclinical formulation literature, and analytically different definitions of circulating phytochemical materially affected interpretation. Formulation can rescue oral exposure for selected phytochemicals under defined conditions, but no delivery technology can presently be regarded as a universal solution. Translation requires evidence connecting formulation mechanism to rigorously defined systemic exposure and, separately, to pharmacodynamic or clinical relevance.
%U https://galaxypub.co/article/can-formulation-rescue-orally-limited-phytochemicals-a-systematic-review-of-bioavailability-gains-mcr3rbpkec5abhr