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AAPS PharmSciTech2024; 25(7); 199; doi: 10.1208/s12249-024-02921-8

Exploring the Dissolution, Solid-state Properties, and Long-term Storage Stability of Cryoprotectant-free Fenbendazole Nanoparticles.

Abstract: Fenbendazole is an antiparasitic drug widely used in veterinary medicine to treat parasitic infections caused in animals like cattle, horses, sheep, and dogs. Recently, it has been repositioned as a potential alternative for cancer treatment. However, it is a highly hydrophobic molecule (0.9 ug/mL), which can compromise its dissolution rate and absorption. Thus, this work aimed to apply a nanotechnological approach to improve drug solubility and dissolution performance. Fenbendazole nanoparticles stabilized by different poloxamers were obtained by lyophilization without cryoprotectants. The behavior of the drug in the solid state was analyzed by X-ray diffractometry, differential scanning calorimetry, and infrared spectroscopy. The nanosystems were also evaluated for solubility and dissolution rate. A long-term stability evaluation was performed for three years at room temperature. The yields of the lyophilization ranged between 75 and 81% for each lot. The nanoparticles showed a submicron size (< 340 nm) and a low polydispersity depending on the stabilizer. The physicochemical properties of the prepared systems indicated a remarkable amorphization of the drug, which influenced its solubility and dissolution performance. The drug dissolution from both the fresh and aged nanosystems was significantly higher than that of the raw drug. In particular, nanoparticles prepared with poloxamer 407 showed no significant modifications in their particle size in three years of storage. Physical stability studies indicated that the obtained systems prepared with P188, P237, and P407 suffered certain recrystallization during long storage at 25 °C. These findings confirm that selected poloxamers exhibited an important effect in formulating fenbendazole nanosystems with improved dissolution.
Publication Date: 2024-08-28 PubMed ID: 39198340PubMed Central: 3580766DOI: 10.1208/s12249-024-02921-8Google Scholar: Lookup
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  • Journal Article

Summary

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The research paper examines the potential enhancement of an antiparasitic drug, fenbendazole’s solubility and dissolution performance using a nanotechnological approach without cryoprotectants.

Objective and Methodology

  • The key aim of this study was to improve the solubility and dissolution rate of fenbendazole, a veterinary antiparasitic drug with potential for treating cancer, through a nanotechnological approach.
  • The scientists used a method known as lyophilization or freeze-drying, where fenbendazole nanoparticles were prepared without cryoprotectants but stabilized with different types of poloxamers, substances commonly used in pharmaceuticals for their stabilizing properties. The success of the lyophilization process was gauged by the yield, which ranged between 75% and 81% per lot.
  • The study also examined how the drug behaves in a solid-state, testing its physicochemical properties using X-ray diffractometry, differential scanning calorimetry, and infrared spectroscopy.
  • After creating the nanoparticles, they were tested for solubility and dissolution rate and were evaluated for long-term stability, over three years, at room temperature.

Findings and Contributions

  • The outcome revealed that fenbendazole nanoparticles were less than 340 nm in size and had low polydispersity, indicating the potential use of various possible pharmaceutical applications.
  • The process resulted in a remarkable amorphization of the drug (conversion of the drug’s crystalline form into a non-crystalline form), which had a significant impact on its solubility and dissolution capability.
  • It was found that the drug dissolution from the fresh and aged nanosystems was much higher than that of the raw drug.
  • In terms of long-term stability, one type of nanoparticles prepared with poloxamer 407 exhibited no significant changes in their particle size after three years of storage. Others prepared with different poloxamers, had some degree of recrystallization during long storage at room temperature.
  • The paper concludes that poloxamers play a key role in formulating fenbendazole nanosystems with improved dissolution, presenting valuable possibilities for future formulation and drug delivery research.

Cite This Article

APA
Bedogni G, Michelena LV, Seremeta K, Okulik N, Salomon C. (2024). Exploring the Dissolution, Solid-state Properties, and Long-term Storage Stability of Cryoprotectant-free Fenbendazole Nanoparticles. AAPS PharmSciTech, 25(7), 199. https://doi.org/10.1208/s12249-024-02921-8

Publication

ISSN: 1530-9932
NlmUniqueID: 100960111
Country: United States
Language: English
Volume: 25
Issue: 7
Pages: 199

Researcher Affiliations

Bedogni, Giselle
  • Instituto de Química Rosario, Consejo Nacional de Investigaciones Científicas y Técnicas (IQUIR-CONICET), Suipacha 531, Rosario, 2000, Argentina.
Michelena, Lina Vargas
  • Instituto de Química Rosario, Consejo Nacional de Investigaciones Científicas y Técnicas (IQUIR-CONICET), Suipacha 531, Rosario, 2000, Argentina.
Seremeta, Katia
  • Departamento de Ciencias Básicas y Aplicadas, Universidad Nacional del Chaco Austral, Cte. Fernández 755, Pcia. Roque Sáenz Peña, Chaco, 3700, Argentina.
  • Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Chaco, Presidencia Roque Sáenz Peña, Argentina.
Okulik, Nora
  • Departamento de Ciencias Básicas y Aplicadas, Universidad Nacional del Chaco Austral, Cte. Fernández 755, Pcia. Roque Sáenz Peña, Chaco, 3700, Argentina.
  • Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Chaco, Presidencia Roque Sáenz Peña, Argentina.
Salomon, Claudio
  • Instituto de Química Rosario, Consejo Nacional de Investigaciones Científicas y Técnicas (IQUIR-CONICET), Suipacha 531, Rosario, 2000, Argentina. csalomon@fbioyf.unr.edu.ar.
  • Área Técnica Farmacéutica, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Suipacha 531, Rosario, 2000, Argentina. csalomon@fbioyf.unr.edu.ar.

MeSH Terms

  • Nanoparticles / chemistry
  • Fenbendazole / chemistry
  • Solubility
  • Drug Stability
  • Freeze Drying / methods
  • Calorimetry, Differential Scanning / methods
  • Drug Storage
  • Particle Size
  • X-Ray Diffraction / methods
  • Drug Liberation
  • Chemistry, Pharmaceutical / methods
  • Poloxamer / chemistry
  • Cryoprotective Agents / chemistry

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