Pharmaceutical Material Engineering: Evaluation of Carvedilol Polymorphs II and III Surface by Packing, Modeling, and Atomic Force Measurements
Solid forms can influence the dissolution, stability, and processability of active pharmaceutical ingredients. However, besides the internal arrangement, crystal habit studies are important, since the exposure of different crystal faces (surfaces) can influence pharmaceutical properties. In this work, we emphasize the importance of the surface study for pharmaceutical materials using the drug carvedilol as a case. We report different crystal surface properties of carvedilol polymorphs II and III. Surfaces were determined by single crystal X-ray diffraction and using BFDH theory. Electron density of the planes was obtained by quantum mechanical calculations. The functionalities available on individual faces were studied together with full interaction maps.
We investigated the correlation between the crystal structure, surface chemistry, and surface properties obtained by atomic force microscopy (AFM). The predominant face in polymorph II is closed packed and presents fewer points for the formation of hydrogen bonds. Polymorph III faces show interaction sites for hydrogen bonding donors. Therefore, crystal-solvent interface interaction between polymorph III and polar solvents is responsible for growth inhibition and habit modification. Also, these findings explain the higher dissolution reported in the literature for polymorph III. The topography of the polymorph II predominant face, observed by AFM, is formed by deposition of layers of unit cells in the a-axis direction. AFM images revealed polymorph III growth by two-dimensional nucleation. DMT modulus obtained by AFM was higher for polymorph III due to its surface structure, with the presence of atoms that participate in hydrogen bonds, contributing to the larger stiffness of polymorph III.
Livia D. Prado, Beatriz F. de C. Patricio, Karen M. Gonçalves, Alexandre B. X. Santos, Murilo L. Bello, Gustavo M. Rocha, Gilberto Weissmüller, Paulo M. Bisch, Jackson A. L. C. Resende, and Helvécio V. A. Rocha
Cryst. Growth Des. 2020
Publication Date:November 12, 2020
https://doi.org/10.1021/acs.cgd.0c01172