Shah Rakhi B, Tawakkul Mobin A, Khan Mansoor A
Division of Product Quality Research, Office of Testing and Research, Office of Pharmaceutical Sciences, Center for Drug Evaluation and Research, Food and Drug Administration, Rockville, Maryland, USA.
AAPS PharmSciTech. 2008;9(1):250-8. doi: 10.1208/s12249-008-9046-8. Epub 2008 Feb 15.
The objective of the present work was to carry out a systematic evaluation of flow of pharmaceutical powders and granules using compendial and non-compendial methods. Angle of repose, bulk density, tapped density, Carr's compressibility index, and Hausner ratios were evaluated. Additionally, flow was characterized using a powder rheometer in which a sensitive force transducer monitors the forces generated as a result of the sample displacement. The critical attributes such as cohesivity index, caking strength, and flow stability were determined for samples. The samples consisted of different grades of magnesium stearate powder including bovine, vegetable, and food grade, physical mixture powder blend consisting of a model formulation, granules prepared by various methods including slugging, high shear granulator, and fluid bed dryer. Lubricant efficiency was also determined for granules lubricated with various concentrations of magnesium stearate. It was observed that the compendial methods were often non-discriminating for minor variations in powder flow. The additional characterization such as cohesivity, and caking strength were helpful in understanding the flow characteristics of pharmaceutical systems. The flow stability test determined that the powders were not affected by the test conditions on the rheometer. The non-compendial tests were discriminating to even minor variations in powder flow.
本研究的目的是使用药典方法和非药典方法对药用粉末和颗粒的流动性进行系统评估。评估了休止角、堆密度、振实密度、卡尔压缩指数和豪斯纳比。此外,使用粉末流变仪对流动性进行表征,其中一个灵敏的力传感器监测由于样品位移而产生的力。测定了样品的关键属性,如内聚性指数、结块强度和流动稳定性。样品包括不同等级的硬脂酸镁粉末,如牛用级、植物用级和食品级,由模型配方组成的物理混合粉末混合物,通过各种方法制备的颗粒,包括制粒、高剪切制粒机和流化床干燥器。还测定了用不同浓度硬脂酸镁润滑的颗粒的润滑效率。观察到药典方法通常对粉末流动性的微小变化没有区分能力。诸如内聚性和结块强度等额外的表征有助于理解药物系统的流动特性。流动稳定性测试确定粉末不受流变仪测试条件的影响。非药典测试甚至对粉末流动性的微小变化也有区分能力。