Otto H. York Department of Chemical, Biological and Pharmaceutical Engineering, New Jersey Institute of Technology, Newark, NJ, USA.
Polymer Processing Institute, Newark, NJ, USA.
Eur J Pharm Biopharm. 2017 Oct;119:68-80. doi: 10.1016/j.ejpb.2017.06.003. Epub 2017 Jun 3.
Nanoextrusion was used to produce extrudates of griseofulvin, a poorly water-soluble drug, with the objective of examining the impact of drug particle size and polymeric matrix type-size of the extrudates on drug dissolution enhancement. Hydroxypropyl cellulose (HPC) and Soluplus® were used to stabilize wet-milled drug suspensions and form matrices of the extrudates. The wet-milled suspensions along with additional polymer (HPC/Soluplus®) were fed to a co-rotating twin-screw extruder, which dried the suspensions and formed various extrudates. The extrudates were dry-milled and sieved into samples with two different sizes. A wet-milled suspension was also spray-dried in comparison to nanoextrusion. Due to differences in polymer-drug miscibility, two forms of the drug were prepared: extrudates with nano/micro-crystalline drug particles dispersed in the HPC matrix as a secondary phase (nano/microcomposites) and extrudates with amorphous drug molecularly dispersed within the Soluplus® matrix (amorphous solid dispersion, ASD). Under non-supersaturating conditions in the dissolution medium, drug nanocrystals in the HPC-based nanocomposites dissolved faster than the amorphous drug in Soluplus®-based ASD. While smaller extrudate particles led to faster drug release for the ASD, such matrix size effect was weaker for the nanocomposites. These findings suggest that nanocrystal-based formulations could outperform ASDs for fast dissolution of low-dose drugs.
纳米挤压被用于制备灰黄霉素的挤出物，灰黄霉素是一种水溶性差的药物，目的是考察药物粒径和挤出物的聚合物基质粒径对药物溶出增强的影响。羟丙基纤维素（HPC）和 Soluplus®被用于稳定湿磨药物混悬液并形成挤出物的基质。湿磨混悬液与额外的聚合物（HPC/Soluplus®）一起被喂入双螺杆挤出机，挤出机干燥混悬液并形成各种挤出物。挤出物经过干磨和筛分，得到两种不同粒径的样品。与纳米挤压相比，还对湿磨混悬液进行了喷雾干燥。由于聚合物-药物相容性的差异，制备了两种药物形式：HPC 基质中纳米/微晶药物颗粒分散的二次相的纳米/微复合材料（纳米/微复合材料）和 Soluplus®基质中无定形药物分子分散的无定形固体分散体（ASD）。在溶解介质中不存在过饱和的情况下，HPC 基纳米复合材料中的药物纳米晶体比 Soluplus®基 ASD 中的无定形药物溶解更快。虽然较小的挤出物颗粒使 ASD 的药物释放更快，但对于纳米复合材料，这种基质尺寸效应较弱。这些发现表明，基于纳米晶体的制剂可能优于 ASDs，用于快速溶解低剂量药物。
