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Influence of Crystal Structure on the Compaction Properties of n-Alkyl 4-Hydroxybenzoate Esters (Parabens)

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Purpose

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.

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Acknowledgments

The authors thank the following: Professor Mino R. Caira and Professor Ferdinando Giordano for providing the detailed crystal structures of the four parabens (Reference 12), Dr. Matthew Mullarney, Dr. Bruno Hancock, and Dr. Chetan Pujara for their valuable advice and industrial mentorship, Dr. Timothy S. Wiedmann for advice with the nanoindentation hardness measurements, the National Science Foundation (NSF) Center for Pharmaceutical Processing Research (CPPR) for major financial support, all members of the Industrial Advisory Board of the CPPR for helpful suggestions, the Supercomputing Institute of the University of Minnesota for financially supporting our use of the Visualization—Workstation Laboratory for the molecular modeling studies, the Characterization Facility of the University of Minnesota for use of an atomic force microscope for measurements of nanoindentation hardness of the parabens crystals, and the Graduate Department of Pharmaceutics, University of Minnesota, for partial financial support.

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Authors and Affiliations

  1. Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Weaver-Densford Hall, 308 Harvard Street SE, Minneapolis, Minnesota, 55455-0343, USA

    Yushi Feng & David J. W. Grant

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  1. Yushi Feng
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  2. David J. W. Grant
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Correspondence to Yushi Feng.

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Feng, Y., Grant, D.J.W. Influence of Crystal Structure on the Compaction Properties of n-Alkyl 4-Hydroxybenzoate Esters (Parabens). Pharm Res 23, 1608–1616 (2006). https://doi.org/10.1007/s11095-006-0275-9

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  • DOI: https://doi.org/10.1007/s11095-006-0275-9

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