Highly Water-Soluble Orotic Acid Nanocrystals Produced by High-Energy Milling

Autor: Nikoletta Fotaki, Gabriel Lima Barros de Araujo, Raimar Löbenberg, Veni Maria Andres Felli, Jéssica de Cássia Zaghi Compri, Takayuki Takatsuka, Nadia Araci Bou-Chacra, Felipe Rebello Lourenço
Rok vydání: 2018
Předmět:
Zdroj: de Cássia Zaghi Compri, J, Andres Felli, V M, Lourenço, F R, Takatsuka, T, Fotaki, N, Löbenberg, R, Bou-Chacra, N A & Barros de Araujo, G L 2019, ' Highly Water-Soluble Orotic Acid Nanocrystals Produced by High-Energy Milling ', Journal of Pharmaceutical Sciences, vol. 108, no. 5, pp. 1848-1856 . https://doi.org/10.1016/j.xphs.2018.12.015
ISSN: 1520-6017
DOI: 10.1016/j.xphs.2018.12.015
Popis: Orotic acid (OA), a heterocyclic compound also known as vitamin B13, has shown potent antimalarial and cardiac protection activities; however, its limited water solubility has posed a barrier to its use in therapeutic approaches. Aiming to overcome this drawback, OA freeze-dried nanocrystal formulations (FA, FB, and FC) were developed by using the high-energy milling method. Polysorbate 80 (FA) and povacoat® (FC) were used alone and combined (FB) as stabilizers. Nanocrystals were fully characterized by dynamic light scattering, laser diffraction, transmission electron microscopy, thermal analysis (thermogravimetry and derivative thermogravimetry, and differential scanning calorimetry), and X-ray powder diffraction revealing an acceptable polydispersity index, changes in the crystalline state with hydrate formation and z-average of 100-200 nm, a remarkable 200-time reduction compared to the OA raw material (44.3 μm). Furthermore, saturation solubility study showed an improvement of 13 times higher than the micronized powder. In addition, cytotoxicity assay revealed mild toxicity for the FB and FC formulations prepared with povacoat®. OA nanocrystal platform can deliver innovative products allowing untapped the versatile potential of this drug substance candidate.
Databáze: OpenAIRE
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