Oleanolic acid (OA) is a pentacyclic triterpenoid widely found in the Oleaceae family, and it represents 3.5% of the dry weight of olive leaves. OA has many pharmacological activities, such as hepatoprotection, anti-inflammatory, anti-oxidant, anti-diabetic, anti-tumor, and anti-microbic activities. Its therapeutic application is limited by its poor water solubility, bioavailability, and permeability. In this study, solid dispersions (SDs) were developed to overcome these OA limitations. Solubility studies were conducted to evaluate different hydrophilic polymers, drug-to-polymer ratios, and preparation methods. Poloxamer 188, Poloxamer 407, and γ-CD exhibited the highest increases in terms of OA solubility, regardless of the method of preparation. Binary systems were characterized using differential scanning calorimetry (DSC), X-ray diffraction (XRPD), and Fourier transform infrared spectroscopy (FTIR). In addition, pure compounds and SDs were analyzed using scanning electron microscopy (SEM) in order to observe both the morphology and the particle surface. In vitro dissolution studies were performed for P407, P188, and γ-CD SDs. Preparation using the solvent evaporation method (SEM) produced the highest increase in the dissolution profiles of all three polymers with respect to the OA solution. Finally, the effect of SDs on OA permeability was evaluated with an in vitro parallel artificial membrane permeability assay (PAMPA). The formulation improved passive permeation across the simulated barrier due to OA increased solubility. The dissolution and PAMPA results indicate that the amorphization of OA by SD preparation could be a useful method to enhance its oral absorption, and it is also applicable on an industrial scale.

Thymoquinone (TQ) is the main constituent of Nigella sativa L. essential oil. In vitro studies have shown its protective effect against H₂O₂-induced oxidative stress in human retinal pigment epithelium cells, and in vivo experiments have demonstrated its effect in decreasing corneal neovascularization and reducing the inflammation in an experimental dry eye model in mice. Its therapeutic use is limited by poor bioavailability, low solubility, and scarce permeability. In this study, two liposomal formulations have been developed, both of which consist of phosphatidylcholine and Plurol Oleique, a liquid lipid, and one of which is coated with 0.1% w/v hyaluronic acid (HA) to increase both TQ solubility and its ocular therapeutic potential. Each formulation has a size <200 nm and an EE% around 70%, determined by scattering techniques and the HPLC-DAD analytical method, respectively, and they result in a 2-fold increase in TQ solubility. HA-coated liposomes are stable over 2 months at +4 °C, and coated and uncoated liposomes present a gradual and prolonged release of TQ. Two cell lines, human corneal epithelial cells (HCEC-2) and human conjunctival epithelial cells (HConEC) were used to investigate the safety of the liposomal formulations. Uptake studies were also performed using fluorescent liposomes. Both liposomes and, in particular, HA-coated liposomes reduce the TQ toxicity observed at high doses in both HCEC-2 and HConEC cells, and both formulations increase the absorption at the cellular level and especially at the nucleus level, with a more pronounced effect for HA-coated liposomes.