Milling is an important secondary processing technique in the manufacture of pharmaceuticals, primarily used as a particle size reduction process. p-Aminobenzoic acid (PABA), m-aminobenzoic acid (MABA), o-aminobenzoic acid (OABA), and carbamazepine (CBZ) are pharmaceutically relevant compounds that can exist in different polymorphic forms with distinct packing motifs and thus different physicochemical properties. A comprehensive study of the effect of milling on the polymorphism of PABA, MABA, OABA, and CBZ was carried out. Milling of PABA in the presence of catalytic amounts of valeric acid or methanol yielded the β polymorph, which is otherwise difficult to obtain in bulk quantities. Milling also proved to be a more convenient method for producing MABA form IV compared with previously reported procedures. Principal component analysis of the pair distribution function-transformed X-ray powder diffraction spectra of ball-milled CBZ samples showed that the milling-induced polymorphic transformation strongly depends on the ball-to-powder ratio. Elusive CBZ form IV could be obtained in pure form by optimizing the milling conditions.

中文翻译：

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球磨在高选择性机械化学多晶型转变中的应用

研磨是药物制造中的一种重要的二次加工技术，主要用作减小粒径的过程。p氨基苯甲酸（PABA），中号氨基苯甲酸（MABA），Ô-氨基苯甲酸（OABA）和卡马西平（CBZ）是药物相关的化合物，可以以不同的多晶型形式存在，具有不同的填充图案，因此具有不同的理化性质。全面研究了铣削对PABA，MABA，OABA和CBZ多态性的影响。在催化量的戊酸或甲醇存在下研磨PABA会产生β多晶型物，否则很难大量获得。与以前报道的方法相比，研磨也被证明是生产MABA晶型IV的一种更方便的方法。球磨CBZ样品的成对分布函数变换的X射线粉末衍射光谱的主成分分析表明，铣削引起的多晶型转变强烈依赖于球粉比。