Innovative formulations to enhance oral bioavailability of Agnus castus extract

The main characteristic constituents of Vitex agnus castus are diterpenes, iridoid glycosides, flavonoids, flavones and triglycerides. Therapeutic indications are premenstrual syndrome and menstrual cycle disorders [1]. In vitro and in vivo experiments have shown that Agnus castus extracts (ACEs) have dopaminergic, prolactin-inhibiting activity [2]. The project is aimed at developing new oral innovative formulations which can overcome the limited oral bioavailability of iridoid glycosides and flavonoids and thus increase the therapeutic efficacy. After optimization of a HPLC-DAD-QTOF analytical method for qualitative and quantitative characterization of consitutents of ACE, nanoemulsions were selected as lipid carriers. The preparations were performed by dissolving extract powder into the oil (triacetin)-surfactant (labrasol)-cosurfactant (Cremophor EL) mixture, adding water. The droplets in the microemulsion appeared dark, and the surroundings bright under Transmission Electron Microscopy with an average diameter of 11.15 ± 0.07nm. Polydispersity (PdI) was 0.07 ± 0.01 measured by a Dynamic Light Scattering. The aqueous solubility of the extract was improved: the extract at the concentration of 40 mg/mL is completely soluble in the nanoemulsion, while the solubility of extract in water resulted less than 6 mg. Finally passive intestinal absorption was evaluated using a Parallel Artificial Membrane Permeation Assay. The test evidenced a good increase of total constituents of the ACE permeated from donor to acceptor compartement.

Acknowledgements: Bionorica Global Research Initiative has supported the study.

References:

[1] European Scientific Cooperative On Phytotherapy, Monographs, 2nd edition. Thieme; 2003; 8 – 13

[2] Jarry H, Leonhardt S, Gorkow C, Wuttke W. In vitro prolactin but not LH and FSH release is inhibited by compounds in extract of Agnus castus: direct evidence for a dopaminergic principle by the dopamine receptor assay. Exp Clin Endocrinol 1994; 102: 448 – 54