Purpose

The aim of this work was to study the effectiveness of various methods for improving the solubility and bioavailability of darunavir by mesoporous carriers and water-soluble polymers in the form of amorphous solid dispersions.

Methods

Preliminarily, using the solvent wetting method, solid dispersions with various water-soluble polymers were obtained, which were tested for the presence of amorphism by X-ray diffraction and scanning electron microscopy methods and to determine the leader in increasing the solubility of darunavir. The selected polymer became the basis for the formulations, which were separately obtained by industrially available hot-melt extrusion and spray-drying methods, mixed with needful excipients and compressed to form dispersible tablets. The resulting tablets were tested in vitro using a dissolution test and in vivo for bioavailability in minipigs.

Results

Of all tested polymer dispersions, the best solubility results have been shown with Eudragit EPO systems for solvent wetting, hot melt extrusion, and fluidized bed methods. These compositions became the basis of polymer formulations that showed better dissolution compared to physical mixture on a mesoporous carrier without polymer. The bioavailability test revealed the highest efficacy of the polymer dispersion on the mannitol particles.

Conclusion

All formulations obtained, containing various solid dispersions, performed better than the original Prezista. This observation allows us to take further steps to reduce the drug load.

中文翻译：

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具有介孔载体和聚合物固体分散体的地芦那韦乙醇化物组合物的药物制备方法和有效性的比较研究

目的

这项工作的目的是研究通过介孔载体和无定形固体分散体形式的水溶性聚合物提高地瑞那韦溶解度和生物利用度的各种方法的有效性。

方法

初步采用溶剂润湿法，获得了具有多种水溶性聚合物的固体分散体，通过 X 射线衍射和扫描电子显微镜方法测试了其是否存在无定形现象，并确定了增加地瑞那韦溶解度的领导者。选定的聚合物成为制剂的基础，通过工业上可用的热熔挤出和喷雾干燥方法分别获得，与所需的赋形剂混合并压制成分散片。使用溶出试验在体外测试所得片剂，并在小型猪体内测试其生物利用度。

结果

在所有测试的聚合物分散体中，Eudragit EPO 系统在溶剂润湿、热熔挤出和流化床方法中的溶解度最好。这些组合物成为聚合物制剂的基础，与在没有聚合物的中孔载体上的物理混合物相比，这些制剂显示出更好的溶解度。生物利用度测试揭示了聚合物分散体对甘露醇颗粒的最高功效。

结论

获得的所有配方，包含各种固体分散体，都比原来的 Prezista 表现更好。这一观察结果使我们能够采取进一步措施来减少药物负荷。