Abstract
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.
Original language | English |
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Pages (from-to) | 1848-1856 |
Number of pages | 9 |
Journal | Journal of Pharmaceutical Sciences |
Volume | 108 |
Issue number | 5 |
Early online date | 30 Dec 2018 |
DOIs | |
Publication status | Published - 1 May 2019 |
Funding
CNPq, (The Brazilian National Council for Scientific and Technological Development) and FAPESP (The São Paulo Research Foundation) are the primary funders, Instituto Adolfo Lutz, Think Corporation, Daido Chemical. Jim Hesson of AcademicEnglishSolutions.com revised the English of this article.
Keywords
- formulation
- nanocrystal(s)
- nanotechnology
- physical characterization
- physicochemical
- polymer(s)
- solubility
- stability
- stabilization
- surfactant(s)
ASJC Scopus subject areas
- Pharmaceutical Science
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