Influence of crystal structure on the compaction properties of n-alkyl 4-hydroxybenzoate esters (parabens).
OBJECTIVE
The aim of the study is to examine the influence of slip planes on the nanoindentation hardness and compaction properties of methyl, ethyl, n-propyl, and n-butyl 4-hydroxybenzoate (parabens).


METHODS
Molecular modeling calculations, embodying the attachment energy concept, were performed to predict the slip planes in the crystal lattices, whereas the nanoindentation hardness of the crystals and the tensile strength of directly compressed compacts were measured.


RESULTS
Unlike the other three parabens, methyl paraben has no slip planes in its crystal lattice, and its crystals showed greater nanoindentation hardness, corresponding to lower plasticity, whereas its tablets exhibited substantially lower tensile strength than those of ethyl, propyl, or butyl paraben.


CONCLUSIONS
The nanoindentation hardness of the crystals and the tensile strength of directly compressed tablets were each found to correlate directly with the absence or presence of slip planes in the crystal structures of the parabens because slip planes confer greater plasticity. This work presents a molecular insight into the influence of crystal structural features on the tableting performance of molecular crystals in general and of crystalline pharmaceuticals in particular.
Feng
Yushi
Y
Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Weaver-Densford Hall, 308 Harvard Street SE, Minneapolis, Minnesota 55455-0343, USA. fengy010@umn.edu
Grant
David J W
DJ
D003460:Crystallization; D004339:Drug Compounding; D004548:Elasticity; D006245:Hardness Tests; D008958:Models, Molecular; D036103:Nanotechnology; D010226:Parabens / Q000737:chemistry*; D011208:Powders; D011310:Preservatives, Pharmaceutical / Q000737:chemistry*; D013607:Tablets; D013718:Tensile Strength
D010226:Parabens; D011208:Powders; D011310:Preservatives, Pharmaceutical; D013607:Tablets