Production of spherical crystals with an appropriate particle size is an important objective for active agents dedicated to direct tablet making (Diao et al. Nat. Mater. 2011, 10, 867−871; Tahara, K. et al. Cryst. Growth Des. 2015, 15, 5149–5156). The material chosen for our experiments, ambroxol hydrochloride, is such a solid compound. The optimal habit for the crystals of direct compressible active agents and additives includes sphericity, proper mean particle size, and appropriate surface. The main objective of the present work is to compare typical and nontypical spherical crystallization methods and to investigate their applicability for ambroxol hydrochloride. The particles were investigated by light microscopy, coupled with an image analyzator program, scanning electron microscopy, powder X-ray diffractometry and differential scanning calorimetry in order to obtain information about particle morphology, mean particle size, aspect ratio, roundness and potential polymorphic transitions. Powder rheology properties were also investigated. The typical crystallization method of quasi-emulsion solvent diffusion was suitable for increasing mean particle size, but large-size spherical crystals did not form. Nontypical spherical crystallization methods (spherical agglomeration and the method of cooling with an alternating temperature profile) caused an increase in mean particle size and an improvement in aspect ratio and roundness. Powder rheology parameters of the spherical agglomeration products improved, too.

中文翻译：

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盐酸氨溴索不同球形结晶方法的比较研究

对于专用于直接制片的活性剂来说，生产具有合适粒径的球形晶体是一个重要的目标（Diao等人， Nat。Mater。 2011年， 10， 867−871；Tahara，K。等。 水晶 增长目标。 2015年， 15， 5149–5156）。我们用于实验的材料氨溴索盐酸盐就是这样一种固体化合物。直接可压缩活性剂和添加剂晶体的最佳习惯包括球形度，适当的平均粒径和适当的表面。本工作的主要目的是比较典型的和非典型的球形结晶方法，并研究它们在盐酸氨溴索中的适用性。通过光学显微镜，图像分析仪程序，扫描电子显微镜，粉末X射线衍射法和差示扫描量热法对颗粒进行了研究，以获得有关颗粒形态，平均粒径，长宽比，圆度和潜在多晶型转变的信息。还研究了粉末流变性能。准乳液溶剂扩散的典型结晶方法适合于增加平均粒径，但没有形成大尺寸的球形晶体。非典型的球形结晶方法（球形团聚和以交替的温度曲线冷却的方法）导致平均粒径的增加以及纵横比和圆度的提高。球形团聚产物的粉末流变学参数也得到改善。