Back to Search
Start Over
Mechanisms of poor oral bioavailability of flavonoid Morin in rats: From physicochemical to biopharmaceutical evaluations
- Source :
- European Journal of Pharmaceutical Sciences. 128:290-298
- Publication Year :
- 2019
- Publisher :
- Elsevier BV, 2019.
-
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.
- Subjects :
- Male
Membrane permeability
Administration, Oral
Biological Availability
Pharmaceutical Science
Morin
Absorption (skin)
Pharmacology
Antioxidants
Permeability
chemistry.chemical_compound
Pharmacokinetics
Oral administration
In vivo
Animals
Humans
Rats, Wistar
Flavonoids
Biological Products
Chemistry
Rats
Bioavailability
Area Under Curve
Drug delivery
Caco-2 Cells
Half-Life
Subjects
Details
- ISSN :
- 09280987
- Volume :
- 128
- Database :
- OpenAIRE
- Journal :
- European Journal of Pharmaceutical Sciences
- Accession number :
- edsair.doi.dedup.....0b34390d764e29cbacb26f4f79d900d2