Department of Chemistry, University of Florence, Via U Schiff 6, 50519 Sesto Fiorentino, Florence, Italy.
National Research Council (CNR), Institute of Chemistry of Organometallic Compounds (ICCOM)-Electron Microscopy Centre (Ce.M.E.), Via Madonna del Piano 10, 50019 Sesto Fiorentino, Florence, Italy.
Molecules. 2022 May 9;27(9):3042. doi: 10.3390/molecules27093042.
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.
齐墩果酸（OA）是一种广泛存在于木犀科的五环三萜，占橄榄油叶干重的 3.5%。OA 具有多种药理活性，如保肝、抗炎、抗氧化、抗糖尿病、抗肿瘤和抗微生物活性。其治疗应用受到其较差的水溶性、生物利用度和通透性的限制。在这项研究中，开发了固体分散体（SDs）来克服这些 OA 限制。进行了溶解度研究以评估不同的亲水性聚合物、药物与聚合物的比例和制备方法。泊洛沙姆 188、泊洛沙姆 407 和 γ-CD 表现出对 OA 溶解度的最高增加，无论制备方法如何。使用差示扫描量热法（DSC）、X 射线衍射（XRPD）和傅里叶变换红外光谱（FTIR）对二元体系进行了表征。此外，使用扫描电子显微镜（SEM）分析了纯化合物和 SDs，以观察形态和颗粒表面。进行了 P407、P188 和 γ-CD SDs 的体外溶解研究。使用溶剂蒸发法（SEM）制备 SD 可使所有三种聚合物的溶解曲线相对于 OA 溶液的增加幅度最大。最后，通过体外平行人工膜渗透测定法（PAMPA）评估 SD 对 OA 渗透性的影响。SD 制剂提高了 OA 溶解度增加的模拟屏障的被动渗透。溶解和 PAMPA 结果表明，通过 SD 制备使 OA 非晶化可能是一种提高其口服吸收的有用方法，并且也适用于工业规模。
