The pharmaceutical technique research group of University of Florence (UNIFI) developed different nanocarriers (microemulsions, solid dispersions and polymeric micelles) to enhance solubility, permeability and pharmaceutical properties of oleanolic acid (OA), a triterpene enriched extract (TTPs ext) and an oleuropein extract (OLE) (Figure 1). All these formulations were tested in terms of water solubility, storage stability, dissolution rate, in vitro release, and passive permeability.

During the year six microemulsions and six solid dispersions with different polymers were developed loading both OA and TTPs ext. The formulations showed good stability at different temperatures and in simulated gastrointestinal fluids. These nanoformulations were also evaluated in terms of passive permeability (PAMPA assay) (Figure 2) and release.

Figure 1

Formulations developed

Figure 2

PAMPA apparatus

Both solid dispersions and microemulsions provided great results in terms of enhancement of the molecules limitations. No permeation is observed by using a solution of free TTPs ext and scarce permeation is observed with OA free solution. By developing the aforementioned formulations, we were able to overcome not also solubility’s limitations and therefore an increment of dissolution rate but also passive permeability across intestinal simulated epithelia.

Hard gelatin capsules were filled with solid dispersions to obtain a formulation to be used commercially. The dissolution rate of OA or TTPs ext was markedly enhanced by solid dipersions. (Figure 3).

Figure 3

Dissolution apparatus

In the last period, UNIFI developed new polymeric micelles loaded with OLE extract (Natac) to improve its solubility (Figure 4). The micelle’s stability was evaluated both as aqueous dispersion and as freeze-dried products with results that predispose the use of freeze-dried products to obtain a longer stability during time.

Figure 4

Oleuropein polymeric micelles