Peer-Reviewed Journal Details
Mandatory Fields
Kamali, N,Gniado, K,McArdle, P,Erxleben, A
2018
July
Organic Process Research & Development
Application of Ball Milling for Highly Selective Mechanochemical Polymorph Transformations
Published
()
Optional Fields
P-AMINOBENZOIC ACID CRYSTAL-STRUCTURE ANTHRANILIC ACID PHYSICOCHEMICAL PROPERTIES DISSOLUTION BEHAVIOR 4-AMINOBENZOIC ACID AMINO-ACIDS FORM-IV CARBAMAZEPINE CRYSTALLIZATION
22
796
802
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 beta 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.
10.1021/acs.oprd.8b00073
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