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采用流化床包衣法制备难溶性药物非诺贝特(FNB)-PEG6000的固体分散体。差示扫描量热法和X-射线粉末衍射法对固体分散体中非诺贝特的物相进行鉴别,结果表明非诺贝特在固体分散体中以微晶形式存在。在含1%十二硫酸钠的水、FASSIF和FESSIF中对其溶出行为进行了考察,结果表明在PEG/FNB的比例为4/1以上,非诺贝特的体外溶出显著提高,30分钟溶出接近完全。然而,在较小PEG/FNB比例时,溶出并未显著提高。经测定血浆中非诺贝酸的含量,对非诺贝特固体分散体小丸的口服生物利用度进行了研究。PEG/FNB比例为3/1和4/1的固体分散体小丸其口服生物利用度相对于微粉化的非诺贝特lipanthyl提高了近3.4和4.4倍,口服生物利用度显著依赖于体外溶出速率。体内外相关性研究表明非诺贝特吸收分数与含1%十二硫酸钠的水、FASSIF和FESSIF中的溶出速率有很好的相关性。非诺贝特-PEG6000固体分散体小丸可用于提高其溶出速率和生物利用度,并具有良好体内外相关性。
A solid dispersion of fenofibrate (FNB) -PEG6000, a poorly soluble drug, was prepared by a fluidized bed coating method. Differential scanning calorimetry and X-ray powder diffraction were used to characterize the phase of fenofibrate in the solid dispersion. The results showed that fenofibrate existed as microcrystals in the solid dispersion. The dissolution behavior in 1% sodium dodecyl sulfate-containing water, FASSIF and FESSIF was investigated. The results showed that the dissolution rate of fenofibrate was significantly increased in vitro when the ratio of PEG / FNB was 4/1 or more, and the dissolution rate in 30 minutes Nearly complete. However, at smaller PEG / FNB ratios, dissolution did not increase significantly. The oral bioavailability of fenofibrate solid dispersion pellets was investigated by measuring the content of fenofibrate in plasma. Solid dispersion pellets with PEG / FNB ratios of 3/1 and 4/1 had an oral bioavailability that was increased by 3.4 and 4.4 fold relative to micronized fenofibrate lipanthyl and that oral bioavailability was significantly dependent on in vitro dissolution rate . In vitro and in vivo correlation studies have shown that fenofibrate absorption fraction has a good correlation with dissolution rate in water containing 1% sodium dodecyl sulfate, FASSIF and FESSIF. Fenofibrate-PEG6000 solid dispersion pellets can be used to increase their dissolution rate and bioavailability with good in vivo and in vitro relevance.