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321496 occurrences (No.66 in the rank) during 5 years in the PubMed. [cache]
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321496 occurrences (No.66 in the rank) during 5 years in the PubMed. [cache]
| 313) Contrast to the solid dispersion and proto drug, the area-under-the-curve (AUC) of T-OA microemulsion and oleic acid solution were significantly enhanced. |
| PMID:24256156 DOI:10.3109/03639045.2013.858739 |
| 2015 Drug development and industrial pharmacy |
| * In-vitro and in-vivo comparison of T-OA microemulsions and solid dispersions based on EPDC. |
| - The goal of this study was to enhance the absorption of a new water-insoluble antitumor lead compound, T-OA (3β-hydroxyolea-12-en-28-oic acid-3, 5, 6-trimethylpyrazin-2-methyl ester). Early-stage preparation discovery concept (EPDC) was employed in this study. Based on this concept, a microemulsion system was chosen as the method of improving bioavailability. The solubility of T-OA was checked in different oils, surfactants and cosurfactants. Ternary phase diagrams were constructed to evaluate the microemulsion domain. Developed high-performance liquid chromatography method was used to determine drug content. The transparent o/w microemulsion formulation composed of oleic acid (oil), Tween 80 (surfactant), ethanol (co-surfactant) and water enhanced the solubility of T-OA up to 20 mg/mL. It was characterized in terms of appearance, content, viscosity, zeta potential, conductivity, morphology and particle size. The particle size distribution, viscosity, conductivity and zeta potential were found to be 70 nm, 15.57 MPa s, 44.1 μS cm(-1) and -0.174, respectively. Oral bioavailability of T-OA microemulsion and oleic acid solution were checked by using rat model. Contrast to the solid dispersion and proto drug, the area-under-the-curve (AUC) of T-OA microemulsion and oleic acid solution were significantly enhanced. The relative bioavailability of T-OA microemulsion was found to be 5654.7%, which is 57-fold higher than the pure drug. Improved T-OA solubility in microemulsion was found sustained 48 h in dilution study. While the solid dispersion may precipitate under the gastrointestinal circumstance based on dilution results. The in-vivo and in-vitro results indicated that, compare to improve the solubility, it is more important to maintain and prolong the T-OA dissolved status, for improvement of the in-vivo absorption. |
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