Jagia Moksh, Trivedi Maitri, Dave Rutesh H
Division of Pharmaceutical Sciences, Arnold & Marie Schwartz College of Pharmacy and Health Sciences, Long Island University, Brooklyn, New York, 11201, USA.
Norwich Pharmaceuticals, Norwich, New York, 13815, USA.
AAPS PharmSciTech. 2016 Aug;17(4):995-1006. doi: 10.1208/s12249-015-0424-8. Epub 2015 Oct 19.
The solvent used for preparing the binder solution in wet granulation can affect the granulation end point and also impact the thermal, rheological, and flow properties of the granules. The present study investigates the effect of solvents and percentage relative humidity (RH) on the granules of microcrystalline cellulose (MCC) with hydroxypropyl methyl cellulose (HPMC) as the binder. MCC was granulated using 2.5% w/w binder solution in water and ethanol/water mixture (80:20 v/v). Prepared granules were dried until constant percentage loss on drying, sieved, and further analyzed. Dried granules were exposed to different percentage RH for 48 h at room temperature. Powder rheometer was used for the rheological and flow characterization, while thermal effusivity and differential scanning calorimeter were used for thermal analysis. The thermal effusivity values for the wet granules showed a sharp increase beginning 50% w/w binder solution in both cases, which reflected the over-wetting of granules. Ethanol/water solvent batches showed greater resistance to flow as compared to the water solvent batches in the wet granule stage, while the reverse was true for the dried granule stage, as evident from the basic flowability energy values. Although the solvents used affected the equilibration kinetics of moisture content, the RH-exposed granules remained unaffected in their flow properties in both cases. This study indicates that the solvents play a vital role on the rheology and flow properties of MCC granules, while the different RH conditions have little or no effect on them for the above combination of solvent and binder.
在湿法制粒中用于制备粘合剂溶液的溶剂会影响制粒终点,还会影响颗粒的热性能、流变性能和流动性能。本研究考察了溶剂和相对湿度(RH)百分比对以羟丙基甲基纤维素(HPMC)为粘合剂的微晶纤维素(MCC)颗粒的影响。使用2.5% w/w的粘合剂溶液在水和乙醇/水混合物(80:20 v/v)中对MCC进行制粒。将制备的颗粒干燥至干燥失重百分比恒定,过筛并进一步分析。将干燥后的颗粒在室温下暴露于不同百分比的RH环境中48小时。使用粉末流变仪进行流变学和流动特性表征,同时使用热导率仪和差示扫描量热仪进行热分析。两种情况下,湿颗粒的热导率值在粘合剂溶液为50% w/w时开始急剧增加,这反映了颗粒的过度湿润。在湿颗粒阶段,乙醇/水溶剂批次的颗粒比水溶剂批次的颗粒表现出更大的抗流动性,而从基本流动能值可以明显看出,在干燥颗粒阶段情况则相反。尽管所使用的溶剂影响了水分含量的平衡动力学,但在两种情况下,暴露于RH环境下的颗粒的流动性能均未受到影响。本研究表明,溶剂对MCC颗粒的流变学和流动性能起着至关重要的作用,而对于上述溶剂和粘合剂的组合,不同的RH条件对它们几乎没有影响。