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Abstract
We recently reported that the absolute oral bioavailability of flavonoid Morin was
extremely low at 0.45%, resulting in unsatisfied therapeutic efficacy in vivo. The
present study was aimed to systemically assess the pre-absorption risks of Morin for
rationale formulation design. Physicochemical properties of Morin were evaluated using
in vitro assays including water solubility and stability in simulated gastric, intestinal
fluids, followed by permeability tests in Caco-2 cells. The results suggested that
both poor solubility and low membrane permeability were rate-limiting steps for oral
absorption of Morin. Pharmacokinetic studies were performed via a series of administration
routes in a dual-vein cannulated rat model. In contrast to high bioavailability (92.92%)
and negligible metabolites of Morin in intraportal administered rats, Morin exhibited
low bioavailability (5.28%) and considerable amount of metabolites in rats following
intraduodenal administration, suggested that intestinal first-pass metabolism made
a major contribution to its poor oral absorption. Morin-phospholipid complex loaded
self-emulsifying drug delivery system (MPC-SENDDS) exhibited comparable plasma concentration
of metabolites to parent drug after oral administration, indicated that MPC-SNEDDS
failed to bypass first-pass metabolism and therefore showed compromised oral absorption
enhancement. The present study could promote the development of more efficient oral
formulations of Morin with optimized absorption enhancement.