The morphology of free-flowed and gravity consolidated crystal powder beds of the alpha and beta polymorphic forms of l-glutamic acid, together with a detailed analysis of particle density and microstructure within alpha form tablets using state -of-the-art X-ray computed tomography (XCT), is presented. The Carr’s index is measured to be 19.7 and 35.2 for the bulk powders of the prismatic alpha form and needle-like beta form, respectively, revealing the alpha forms increased powder flowability versus the beta form. XCT reveals the alpha form consolidates under gravity more efficiently than beta, where the final measured bed density of the alpha form is 0.724 g/cm³ compared to 0.248 g/cm³ for the beta form, which is found to be caused by the inability of the beta particles to pack efficiently along their needle axis. Tabletting studies reveal that the alpha form consolidates into compacts of intermediate tensile strength, whereas the beta form cannot be compacted under these conditions. XCT analysis of tablets formed from α-form crystals reveals two discrete density regimes, one low-density region of fine powder which accounts for 53.8% of the compact, and high-density regions of largely intact single crystals which account for 44.2% of the compact. Further analysis of the tablet microstructure reveals that the crystal particles are generally orientated with their basal {0 0 1} plane, normal to the compaction force and that small microcracks which appear within the particles generally occur perpendicular to the surface and are orientated through possible {1 1 0} and {1 0 1} fracture planes. XCT also reveals evidence for incipient transformation between the meta-stable alpha to stable beta phase at concentrations below that detected using laboratory X-ray diffraction. The results show that XCT can accurately measure the extent of tapping induced densification and reveals the powder bed mesostructure characteristics and tablet microstructure for the two polymorphic forms of alpha and beta l-glutamic acid.

中文翻译：

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通过X射线计算机断层摄影术测量L-谷氨酸晶体的颗粒堆积，以了解粉末流动和固结行为

的形态自由流动和重力合并的α晶体粉末床和的测试多晶型形式升与颗粒密度和微结构的使用状态的α形式的片剂中的详细的分析-谷氨酸，一起-of先进透视介绍了计算机断层扫描（XCT）。棱柱形α型和针状β型散装粉末的Carr指数分别为19.7和35.2，表明α型相对于β型粉末流动性增加。XCT显示，α形式在重力作用下比β形式更有效地固结，最终测得的α形式床层密度为0.724 g / cm ^3，而0.248 g / cm ³对于β形式，发现是由于β颗粒不能沿其针轴有效堆积所致。压片研究表明，α形式固结为具有中等拉伸强度的压坯，而β形式在这些条件下无法压实。由α形晶体形成的片剂的XCT分析显示出两种离散的密度模式，一种低密度区域的细粉占致密粉的53.8％，另一种高度完整的单晶体的高密度区域，其占致密粉的44.2％。紧凑。对药片微结构的进一步分析表明，晶体颗粒通常以其基{0 0 1}面取向，垂直于压紧力的方向，颗粒中出现的小微裂纹通常垂直于表面，并通过可能的{1 1 0}和{1 0 1}断裂面定向。XCT还揭示了在低于使用实验室X射线衍射检测到的浓度下，亚稳定的α相到稳定的β相之间发生初期转变的证据。结果表明，XCT可以准确测量出丝锥引起的致密化程度，并揭示了α和β两种多晶型形式的粉末床介观结构特征和片剂微观结构1-谷氨酸。