Solubility and Permeability Enhancement of Oleanolic Acid by Solid Dispersion in Poloxamers and γ-CD

Abstract

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.

Stabilized Astaxanthin Nanoparticles Developed Using Flash Nanoprecipitation to Improve Oral Bioavailability and Hepatoprotective Effects

“…In the present study, sNP/AX might have facilitated the absorption of AX through enterocytes by improving its dissolution in the gastrointestinal tract and reducing the thickness of the diffusion layer. Moreover, P407, used as a stabilizer in the sNP/AX, might partially accelerate the permeation of AX through enterocytes, because amphiphilic polymers act as a permeability enhancer [41]. To date, very few studies have reported the absolute oral BA of AX, and only the enhancement of its pharmacokinetic parameters has been reported [42,43].…”

Microemulsions Enhance the In Vitro Antioxidant Activity of Oleanolic Acid in RAW 264.7 Cells

“…Many properties regulate passive absorption through the GI tract, among them: log P, log D, molecular weight, ionization, and ability to form hydrogen bonds. All these parameters are useful in predicting passive uptake processes, but the use of in vitro artificial membrane assays proves useful in completing the prediction of passive uptake processes [ 36 , 37 , 38 , 39 ]. This non-cell-based model is widely contemplated as both robust and reproducible.…”

Unlocking the Potential of Oleanolic Acid: Integrating Pharmacological Insights and Advancements in Delivery Systems

“…In vitro dissolution studies for P407, P188, and γ-CD SDs showed the solvent evaporation method as the most effective in enhancing dissolution compared to the OA solution. An in vitro parallel artificial membrane permeability assay (PAMPA) demonstrated improved passive permeation, as demonstrated in Figure 10 , indicating that the amorphization of OA by SD preparation could be a promising method for enhancing its oral absorption, applicable on an industrial scale [ 164 ].…”

“… Schematic representation of preparation of the solid dispersions using the physical mixture, kneading, and the solvent evaporation method. Reproduced with permission from [ 164 ], MDPI, 2022. …”