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评估不同硬脂酸镁多晶型物的粉末流变性和热分析的效果。

To evaluate the effect of various magnesium stearate polymorphs using powder rheology and thermal analysis.

机构信息

Division of Pharmaceutical Sciences, Long Island University, 75 Dekalb Avenue, Brooklyn, NY 11201, USA.

出版信息

Drug Dev Ind Pharm. 2012 Dec;38(12):1470-8. doi: 10.3109/03639045.2011.653812. Epub 2012 Feb 5.

DOI:10.3109/03639045.2011.653812
PMID:22304483
Abstract

The effects of magnesium stearate (MgSt) polymorphs-anhydrate (MgSt-A), monohydrate (MgSt-M), and dihydrate (MgSt-D)-on rheological properties of powders were evaluated using techniques such as atomic analysis and powder rheometry. Additional evaluation was conducted using thermal analysis, micromeritics, and tableting forces. In this study, binary ratios of neat MgSt polymorphs were employed as lubricants in powder blends containing acetaminophen (APAP), microcrystalline cellulose (MCC), and lactose monohydrate (LAC-M). Powder rheometry was studied using permeability, basic flow energy (BFE), density, and porosity analysis. Thermal conductivity and differential scanning calorimetric analysis of MgSt polymorphs were employed to elucidate MgSt effect on powder blends. The impact of MgSt polymorphs on compaction characteristics were analyzed via tablet compression forces. Finally, the distribution of atomized magnesium (Mg) ions as a function of intensity was evaluated using laser-induced breakdown spectroscopy (LIBS) on tablets. The results from LIBS analysis indicated the dependency of the MgSt polymorphic forms on the atomized Mg ion intensity, with higher Mg ion intensity suggesting higher lubricity index (i.e. greater propensity to over-lubricate). The results from lubricity index suggested the tendency of blends to over-lubricate based on the MgSt polymorphic forms. Finally, tableting forces suggested that MgSt-D and MgSt-A offered processing benefits such as lower ejection and compression forces, and that MgSt-M showed the most stable compression force in single or combined polymorphic ratios. These results suggested that the initial moisture content, crystal arrangement, intra- and inter-molecular packing of the polymorphs defined their effects on the rheology of lubricated powders.

摘要

采用原子分析和粉末流变性等技术评价了硬脂酸镁(MgSt)多晶型物一水合物(MgSt-A)、一水合物(MgSt-M)和二水合物(MgSt-D)对粉末流变性能的影响。还通过热分析、微尺度和压片力对其进行了额外评估。在这项研究中,将纯 MgSt 多晶型物的二元比例用作含有对乙酰氨基酚(APAP)、微晶纤维素(MCC)和一水乳糖(LAC-M)的粉末混合物中的润滑剂。使用透气性、基本流动能量(BFE)、密度和孔隙率分析研究了粉末流变性。采用热导率和差示扫描量热法分析了 MgSt 多晶型物,以阐明 MgSt 对粉末混合物的影响。通过片剂压缩力分析了 MgSt 多晶型物对压缩特性的影响。最后,使用激光诱导击穿光谱法(LIBS)在片剂上评估了雾化镁(Mg)离子随强度的分布。LIBS 分析结果表明,MgSt 多晶型物形式依赖于雾化 Mg 离子强度,较高的 Mg 离子强度表明较高的润滑性指数(即更倾向于过度润滑)。润滑性指数的结果表明,基于 MgSt 多晶型物形式,混合物有过度润滑的趋势。最后,压片力表明,MgSt-D 和 MgSt-A 提供了加工益处,例如较低的推出和压缩力,而 MgSt-M 在单一或组合多晶型物比例下表现出最稳定的压缩力。这些结果表明,多晶型物的初始水分含量、晶体排列、分子内和分子间的堆积方式决定了它们对润滑粉末流变性能的影响。

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