Journal
JOURNAL OF PHARMACEUTICAL SCIENCES
Volume 102, Issue 1, Pages 73-83Publisher
WILEY-BLACKWELL
DOI: 10.1002/jps.23334
Keywords
crystal morphology; crystal habit; crystal shape; crystal polymorphism; in silico modeling; force field; structure-morphology relationship; X-ray diffractometry; tableting; diabetes
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The growing interest of pharmaceutical companies toward the crystal morphology prediction of active pharmaceutical ingredients is a consequence of the dramatic effect of the crystal habit on the tableting behavior of drugs. In order to help the optimization of the industrial process, molecular mechanics calculations together with X-ray diffraction analysis and optical microscopy (OM) were used to shed light over the structural properties of N-(butylcarbamoyl)-4-methylbenzenesulfonamidecommercially known as tolbutamidea drug used in the management of type II diabetes, especially in elderly diabetics because of its rapid metabolism. As there are several known polymorphs of this molecule, we first defined, by means of a quantitative phase analysis, performed by X-ray powder diffraction, which and how much each of the five crystallographic structures present in the Cambridge Crystallographic Database represent the commercial crystalline powder. The structures of the resulting candidates were first analyzed by means of molecular mechanics, and the crystal morphologies of the compounds were therefore predicted and compared with the ones observed by means of OM. Analogies and differences among the different morphologies, together with the potential role of crystallization solvents, were commented in the attempt to bridge the gap between the molecular structurethat is, the atomic point of viewand the crystal habit. (c) 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:7383, 2013
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