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 gamma-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 gamma-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.

Solubility and Permeability Enhancement of Oleanolic Acid by Solid Dispersion in Poloxamers and γ-CD / Chiara De Stefani, Jessika Lodovichi, Laura Albonetti, Maria Cristina Salvatici, José Carlos Quintela, Anna Rita Bilia, Maria Camilla Bergonzi. - In: MOLECULES. - ISSN 1420-3049. - ELETTRONICO. - (2022), pp. 0-0.

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

Chiara De Stefani;Jessika Lodovichi;Anna Rita Bilia;Maria Camilla Bergonzi
2022

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 gamma-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 gamma-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.
0
0
Chiara De Stefani, Jessika Lodovichi, Laura Albonetti, Maria Cristina Salvatici, José Carlos Quintela, Anna Rita Bilia, Maria Camilla Bergonzi
File in questo prodotto:
File Dimensione Formato  
molecules-27-03042-pubblicato.pdf

accesso aperto

Tipologia: Pdf editoriale (Version of record)
Licenza: Open Access
Dimensione 3.66 MB
Formato Adobe PDF
3.66 MB Adobe PDF Visualizza/Apri

I documenti in FLORE sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2158/1279419
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 1
  • ???jsp.display-item.citation.isi??? ND
social impact