Comparative physical, mechanical and crystallographic properties of a series of gemfibrozil salts

Sarah E. David, Miren Ramirez, Peter Timmins, Barbara R. Conway

Research output: Contribution to journalSpecial issue

Abstract

Objectives Understanding the impact of the counterion on the properties of an acidic or basic drug may influence the choice of salt form, especially for less potent drugs with a high drug load per unit dose. The aim of this work was to determine the influence of the hydrogen bonding potential of the counterion on the crystal structure of salts of the poorly soluble, poorly compressible, acidic drug gemfibrozil and to correlate these with mechanical properties. Methods Compacts of the parent drug and the salts were used to determine Young's modulus of elasticity using beam bending tests. Crystal structures were determined previously from X-ray powder diffraction data. Key findings The free acid, tert-butylamine, 2-amino-2-methylpropan-1-ol and 2-amino-2-methylpropan-1, 3-diol salts had a common crystal packing motif of infinite hydrogen-bonded chains with cross-linking between pairs of adjacent chains. The tromethamine (trsi) salt, with different mechanical properties, had a two-dimensional sheet-like network of hydrogen bonds, with slip planes, forming a stiffer compact. Conclusions The type of counter ion is important in determining mechanical properties and could be selected to afford slip and plastic deformation.

Original languageEnglish
Pages (from-to)1519-1525
Number of pages7
JournalJournal of Pharmacy and Pharmacology
Volume62
Issue number11
Early online date20 Jul 2010
DOIs
Publication statusPublished - Nov 2010

Fingerprint

Gemfibrozil
Salts
Pharmaceutical Preparations
Elastic Modulus
Hydrogen
Powder Diffraction
Tromethamine
Hydrogen Bonding
X-Ray Diffraction
Plastics
Ions
Acids

Keywords

  • crystal
  • gemfibrozil
  • salts
  • slip plane
  • Young's modulus

Cite this

David, Sarah E. ; Ramirez, Miren ; Timmins, Peter ; Conway, Barbara R. / Comparative physical, mechanical and crystallographic properties of a series of gemfibrozil salts. In: Journal of Pharmacy and Pharmacology. 2010 ; Vol. 62, No. 11. pp. 1519-1525.
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Comparative physical, mechanical and crystallographic properties of a series of gemfibrozil salts. / David, Sarah E.; Ramirez, Miren; Timmins, Peter; Conway, Barbara R.

In: Journal of Pharmacy and Pharmacology, Vol. 62, No. 11, 11.2010, p. 1519-1525.

Research output: Contribution to journalSpecial issue

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AB - Objectives Understanding the impact of the counterion on the properties of an acidic or basic drug may influence the choice of salt form, especially for less potent drugs with a high drug load per unit dose. The aim of this work was to determine the influence of the hydrogen bonding potential of the counterion on the crystal structure of salts of the poorly soluble, poorly compressible, acidic drug gemfibrozil and to correlate these with mechanical properties. Methods Compacts of the parent drug and the salts were used to determine Young's modulus of elasticity using beam bending tests. Crystal structures were determined previously from X-ray powder diffraction data. Key findings The free acid, tert-butylamine, 2-amino-2-methylpropan-1-ol and 2-amino-2-methylpropan-1, 3-diol salts had a common crystal packing motif of infinite hydrogen-bonded chains with cross-linking between pairs of adjacent chains. The tromethamine (trsi) salt, with different mechanical properties, had a two-dimensional sheet-like network of hydrogen bonds, with slip planes, forming a stiffer compact. Conclusions The type of counter ion is important in determining mechanical properties and could be selected to afford slip and plastic deformation.

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