Exploring the Dissolution, Solid-state Properties, and Long-term Storage Stability of Cryoprotectant-free Fenbendazole Nanoparticles.
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
fenbendazole
freeze-drying
nanoparticles
poloxamer
stability
Journal
AAPS PharmSciTech
ISSN: 1530-9932
Titre abrégé: AAPS PharmSciTech
Pays: United States
ID NLM: 100960111
Informations de publication
Date de publication:
28 Aug 2024
28 Aug 2024
Historique:
received:
06
06
2024
accepted:
14
08
2024
medline:
31
8
2024
pubmed:
31
8
2024
entrez:
28
8
2024
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 39198340
doi: 10.1208/s12249-024-02921-8
pii: 10.1208/s12249-024-02921-8
doi:
Substances chimiques
Fenbendazole
621BVT9M36
Poloxamer
106392-12-5
Cryoprotective Agents
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
199Informations de copyright
© 2024. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.
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