Drug Delivery and Disposition, KU Leuven, Leuven, Belgium.
J Pharm Sci. 2013 Nov;102(11):3966-77. doi: 10.1002/jps.23700. Epub 2013 Aug 14.
The objective of this study was to compare agglomerations by melt and steam granulation of ordered, COK-12, and disordered, Syloid(®) 244 FP (244), mesoporous silica material. Poloxamer 188 (P188) and polyvinylpyrrolidone K25 (PVP) were chosen as binders for melt and steam granulation, respectively. The poorly water-soluble compound, itraconazole (ITZ), was selected for the development of an immediate-release oral dosage form. Steam granulation resulted in the largest granules, however, the slowest release. Compression behavior and tablet properties of steam-granulated material prepared with COK-12 and 244 were similar. As determined by X-ray powder diffraction, melt granulation resulted in the most ITZ to extract from the pores during processing. However, the enhanced release rate was still maintained when compared with the crystalline form. Moreover, no additional drug extraction was observed following the 6 month storage in 25°C/60% relative humidity (RH) and 40°C/75%RH. P188 diffraction peaks were present in the 244 melt-granulated material, but disappeared because of the degradation following 1 week in 40°C/75%RH conditions. The differential scanning calorimetry analysis indicated that the degradation of P188 already occurred during the granulation process itself. Based on these results, steam granulation with PVP is the preferred method over melt granulation with P188.
本研究旨在比较熔融和蒸汽制粒对有序 COK-12 和无序 Syloid(®) 244 FP（244）介孔硅材料的团聚作用。聚氧乙烯-聚氧丙烯嵌段共聚物 188（P188）和聚乙烯吡咯烷酮 K25（PVP）分别被选为熔融和蒸汽制粒的粘合剂。选择疏水性差的伊曲康唑（ITZ）作为模型药物，开发速释口服剂型。蒸汽制粒得到的颗粒最大，但释放最慢。用 COK-12 和 244 制备的蒸汽制粒材料的压缩行为和片剂性能相似。X 射线粉末衍射表明，熔融制粒过程中从孔中提取的 ITZ 最多。然而，与结晶形式相比，释放速率仍然得到提高。此外，在 25°C/60%相对湿度（RH）和 40°C/75%RH 下储存 6 个月后，没有观察到额外的药物提取。244 熔融制粒材料中存在 P188 的衍射峰，但在 40°C/75%RH 条件下 1 周后，由于降解而消失。差示扫描量热分析表明，P188 的降解在制粒过程中已经发生。基于这些结果，与 P188 熔融制粒相比，PVP 蒸汽制粒是首选方法。
