Department of Pharmaceutics, University of Minnesota, Minneapolis, Minnesota 55455; Characterization Facility, University of Minnesota, Minneapolis, Minnesota 55455.
Department of Pharmaceutics, University of Minnesota, Minneapolis, Minnesota 55455.
J Pharm Sci. 2018 Jan;107(1):231-238. doi: 10.1016/j.xphs.2017.08.021. Epub 2017 Sep 9.
The average grain size of a crystalline material can be determined from the γ-profile of Debye rings in 2-dimensional X-ray diffraction frames. Our objectives were to: (1) validate the method for organic powders and use it to determine the grain size in intact tablets, and (2) demonstrate the pharmaceutical application of this technique by determining the grain size of the active pharmaceutical ingredient in marketed formulations. Six sieve fractions of sucrose were prepared and the particle size distribution was confirmed by laser diffraction. Their average grain size was determined from the 2-dimensional X-ray diffraction frames by the γ-profile method. For particles <90 μm (based on sieving), the average particle size determined by the 3 methods were in good agreement. When these particles were compressed, there was no discernible change in the sucrose grain size in tablets. When the particles were >250 μm, compression resulted in a mixture of large grains and fine powder. The grain size of acetaminophen in 11 marketed tablet formulations was determined to be either ∼35 μm or ∼80 μm. This nondestructive technique can therefore be potentially useful to estimate the grain size of crystalline formulation components in intact tablets.
结晶材料的平均晶粒尺寸可以通过二维 X 射线衍射环的γ谱来确定。我们的目标是：（1）验证该方法对有机粉末的适用性，并将其用于测定完整片剂的晶粒尺寸；（2）通过测定市售制剂中活性药物成分的晶粒尺寸，展示该技术的药物应用。制备了六个蔗糖筛分级分，并通过激光衍射确认了粒径分布。通过γ谱法从二维 X 射线衍射环中确定它们的平均晶粒尺寸。对于<90μm的颗粒（基于筛分），这 3 种方法确定的平均粒径非常吻合。当这些颗粒被压缩时，片剂中蔗糖晶粒尺寸没有明显变化。当颗粒>250μm时，压缩会导致大颗粒和细粉的混合物。11 种市售片剂制剂中对乙酰氨基酚的晶粒尺寸被确定为 35μm 或 80μm。因此，这种非破坏性技术可能有助于估计完整片剂中结晶配方成分的晶粒尺寸。
