Drug Delivery and Disposition, KU Leuven, Leuven, Belgium.
J Pharm Sci. 2013 Nov;102(11):3978-86. doi: 10.1002/jps.23699. Epub 2013 Aug 14.
The objectives of this study were to identify the key process parameters during steam granulation of disordered mesoporous silica material Syloid® 244 FP (244) and to compare two different binders: polyvinylpyrrolidone (PVP) K25 and hydroxypropylmethyl cellulose (HPMC). Itraconazole (ITZ) was selected as the model compound for the development of an oral dosage form for enhanced release. Six factors: binder content, steam amount, mixing time, impeller speed, spray pause time, and filler content were investigated using a two-level quarter-fraction factorial design of experiment (DOE) for each binder type. As experimental responses, characteristics correlating to both granules and tablets were selected. Granules prepared from PVP resulted in an overall higher bulk density, granule size, increased flow properties, and better compression and compaction behavior. Although granulation with PVP resulted in the most ITZ to extract from the pores during processing, the premature drug release was less than 5%. The results of the DOE indicate that the risk of extracting the drug from the pores during processing is governed both by the process parameters and the binder properties. Centerpoint replicates of granules prepared with HPMC were highly variable.
本研究的目的是确定无序介孔硅材料 Syloid® 244 FP（244）在蒸汽造粒过程中的关键工艺参数，并比较两种不同的粘合剂：聚乙烯吡咯烷酮（PVP）K25 和羟丙基甲基纤维素（HPMC）。伊曲康唑（ITZ）被选为开发用于增强释放的口服剂型的模型化合物。使用每一种粘合剂类型的两级四分位部分因子设计实验（DOE），研究了六个因素：粘合剂含量、蒸汽量、混合时间、搅拌器速度、喷雾暂停时间和填充剂含量。作为实验响应，选择了与颗粒和片剂都相关的特性。由 PVP 制备的颗粒总体上具有更高的堆密度、颗粒尺寸、增加的流动性能以及更好的压缩和压实性能。尽管用 PVP 进行造粒会导致在加工过程中从孔中提取出更多的 ITZ，但药物的早期释放量仍小于 5%。DOE 的结果表明，在加工过程中从孔中提取药物的风险既受工艺参数又受粘合剂性能的控制。用 HPMC 制备的颗粒的中心点重复实验结果高度可变。
