Formulation of a Phenol-Rich Extract from Unripe Olives (Olea europaeaL.) in Microemulsion to Improve Its Solubility and Intestinal Permeability

The beneficial properties of phenolic compounds fromOlea europaeaL. are well-known. An olive extract (OE) was prepared from unripe olives (Moraiolo cultivar). The study aimed to formulate OE into a microemulsion (ME) in oral dosage form. OE was extracted from olives with EtOH:H2O (80:20) and characterized by HPLC-DAD. ME composition was stated by a solubility and pseudo-ternary diagram. The ME was chemically and physically characterized, and its stability at 4 degrees C was analyzed for three months. The ability of the formulation to ameliorate the solubility and the intestinal permeability of OE was evaluated by a Parallel Artificial Membrane Permeability Assay (PAMPA) assay and Caco-2 cells. The total phenolic content of the extract was 39%w/w. The main constituent was oleuropein (31.0%), together with ligstroside (3.1%) and verbascoside (2.4%). The ME was prepared using Capryol 90 as the oily phase, and Cremophor EL and Transcutol (2:1) as surfactant and co-surfactant, respectively. ME droplet size was 14.03 +/- 1.36 nm, PdI 0.20 +/- 0.08, zeta-potential -1.16 +/- 0.48. Stability of ME was confirmed for at least three months. The formulation was loaded with 35 mg/mL of OE, increasing the solubility of the extract by about four times. The enhanced permeability of OE was evaluated by PAMPA, as demonstrated by the Pe value (1.44 +/- 0.83 x 10(-6)cm/s for OE hydroalcoholic solution, 3.74 +/- 0.34 x 10(-6)cm/s for OE-ME). Caco-2 cell transport studies confirmed the same results: P(app)was 16.14 +/- 0.05 x 10(-6)cm/s for OE solution and 26.99 +/- 0.45 x 10(-6)cm/s for OE-ME. ME proved to be a suitable formulation for oral delivery.