Purpose. To understand the influence of polymorphic structure on the tableting properties of sulfamerazine. Methods. Bulk powders of sulfamerazine polymorph I and of two batches, II(A) and II(B) of different particle size, of polymorph II were crystallized. The powders were compressed to form tablets whose porosity and tensile strength were measured. The relationships between tensile strength, porosity and compaction pressure were analyzed by the method developed by Joiris, E., et al. Pharm. Res. 15:1122-1130 (1998). Results. The sensitivity of tensile strength to compaction pressure, known as the tabletability, follows the order. I ≫ II(A) > II(B) and the porosity at the same compaction pressure, which measures the compressibility, follows the order, I ≪ II(A) < II(B). Therefore, the superior tabletability of I over II(A) or II(B) is attributed to its greater compressibility. Molecular simulation reveals slip planes in crystals of I but not in II. Slip planes provide I crystals greater plasticity and therefore greater compressibility and tabletability. Larger crystal size of II(B) than of II(A) leads to fewer contact points between crystals in the tablets and results in a slightly lower tabletability. Conclusions. Slip planes confer greater plasticity to crystals of I than II and therefore greater tabletability.
Bibliographical noteFunding Information:
We thank the American Foundation for Pharmaceutical Education for awarding a Pre-Doctoral Fellowship to C. Sun. We also thank the Supercomputing Institute of the University of Minnesota for financially supporting our use of the Medicinal Chemistry / Supercomputing Institute Visualization − Workstation Laboratory.
- Slip planes
- Sulfamerazine polymorphs
- Tensile strength