| Ethaselen(Eb for short) using Ebselen as a lead compound has been synthesized, and it is a new organic selenium compound. It was evident that Ethaselen had significantly anti-tumor effect by animal test and cells experiments in vitro.Unfortunately, Eb is practically insoluble in water and many organic solvents (e.g. methanol, ethanol, chloroform, ether) and is hardly absorbed in gastrointestinal tract. Eb has very low bioavailability for the oral route, and clinical application is limited greatly. However, its solid dispersion with polyvinylpyrrolidone (PVP) of which the solubility was very good could possibly improve all these drawbacks.First, the UV analytical methods of Eb granules were set up. By the single factors, the preparation conditions of the granules of Eb with PVP were screened and optimized. The best preparation conditions of Eb/PVP were as follows:particle size of5μm, host-guest weight ratio(20:1), proper amount of ethanol (the ratio of quality to volume was1g:4mL), ultrasonating for10minutes, stirring for30minutes at room temperature, evaporating of solvent by heating, drying in the oven (110℃), and the relative humility of production environment below65%.Eb and its physical mixture were compared, and the solubility in water and the dissolution rate of Eb/PVP were studied. The water solubility and dissolution rate of Eb were dramatically enhanced by the preparation with PVP. The dissolution rate of Eb was improved with the increase of PVP content in the solid dispersion. The dissolution rate of the ratio of Eb to PVP with1:10was13%higher than that of1:4.The stability of Eb granules was studied. Under60℃and45001ux±5001ux light condition, the granules of Eb was stored for ten days and sampled at5and10days, respectively. The content and related substances accord with the quality standard.The results of the pharmacokinetic and bioavailability studies showed that the bioavailability of Eb/PVP granules and dispersible tablets through the oral route had little difference. |
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