TY - JOUR
T1 - Comparative physical, mechanical and crystallographic properties of a series of gemfibrozil salts
AU - David, Sarah E.
AU - Ramirez, Miren
AU - Timmins, Peter
AU - Conway, Barbara R.
PY - 2010/11
Y1 - 2010/11
N2 - 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.
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.
KW - crystal
KW - gemfibrozil
KW - salts
KW - slip plane
KW - Young's modulus
UR - http://www.scopus.com/inward/record.url?scp=78649670608&partnerID=8YFLogxK
UR - http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)2042-7158
U2 - 10.1111/j.2042-7158.2010.01025.x
DO - 10.1111/j.2042-7158.2010.01025.x
M3 - Article
C2 - 21039537
AN - SCOPUS:78649670608
VL - 62
SP - 1519
EP - 1525
JO - Journal of Pharmacy and Pharmacology
JF - Journal of Pharmacy and Pharmacology
SN - 0022-3573
IS - 11
ER -