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- W2897845972 abstract "Many potential drug candidates are excluded from consideration at the early stages of research and development because of their poor solubility in the biological fluids. Even toxicological tests in vivo become impossible, since there is no way to administer the drug to an animal. The purpose of this study was to explore the feasibility of developing bioavailable formulations of very poorly soluble compounds like soloxolon methyl (water solubility <0.3 μg/ml, 6∙10–13 M). The three-component solid dispersions were prepared by freeze-drying of β-glycine suspensions in a solution of soloxolon methyl and polyethylene glycol in tert-butanol. The β-glycine played the role of a disintegrant, and polyethylene glycol – of a carrier. The cytotoxic activity was tested in vitro with respect to human cervical carcinoma cells; hematological toxicity was tested in vivo on mice. Soloxolon methyl solubility from the formulations increased ∼25–10 times (7.3–3.1 vs 0.3 μg/ml), whereas the half maximal inhibitory concentration decreased 1.3–1.9 times as compared with сrude soloxolon methyl. The in vivo testing has shown the absence of hematological toxicity. The methodology described in this work is transferrable to other poorly water-soluble active pharmaceutical ingredients that cannot be micronized/solubilized by routine techniques in a straightforward way." @default.
- W2897845972 created "2018-10-26" @default.
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- W2897845972 date "2019-02-01" @default.
- W2897845972 modified "2023-10-15" @default.
- W2897845972 title "Increasing bioavailability of very poorly water-soluble compounds. A case study of an anti-tumor drug, soloxolon methyl" @default.
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- W2897845972 doi "https://doi.org/10.1016/j.jddst.2018.10.025" @default.
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