Acta Crystallographica Section A Foundations of Crystallography, 2009
Today's most interesting samples rarely make our jobs easy for us. Unfortunately many of the syst... more Today's most interesting samples rarely make our jobs easy for us. Unfortunately many of the systems that we want to study crystallise as very tiny crystals. This can be particularly true of pharmaceuticals but is a widespread difficulty in many areas of chemistry and materials where we repeatedly face these challenges. Constant pressure to deliver high quality results and extract as much information as possible are coupled with pressures to do so both cost and time efficiently. The combination of the Rigaku MicroMax 007HF generator with the RAPID II unique curved, large area image plate detector already provides a hugely flexible tool to address many of these challenges. Advances in optics now mean that this powerful combination of generator and detector can be used with both Mo and Cu radiation (or Cu and Cr) on the same instrument, just by swapping the rapidly interchangeable targets. The image plate is highly sensitive for all these wavelengths providing for high quality data without compromise. The extremely large active area of the detector (-60 to 144°) allows a massive solid angle of data to be collected in a single exposure; ideal for fast high resolution Cu data for absolute configuration determination and equally for very high resolution data with Mo radiation. The exceptional low noise and wide dynamic range also suit the long exposure times often necessary for very tiny crystals -even with a brilliant source -without saturation or excessive noise problems. This single instrument is so versatile that it can replace several others -for single crystal diffraction studies (both small and macromolecular) at both wavelengths as well as powder diffraction. Results of studies using this new dual wavelength capability system will be presented.
Understanding the impact of the counterion on the properties of an acidic or basic drug may inf... more 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. 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. 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. The type of counter ion is important in determining mechanical properties and could be selected to afford slip and plastic deformation.
Acta Crystallographica Section A Foundations of Crystallography, 2009
Today's most interesting samples rarely make our jobs easy for us. Unfortunately many of the syst... more Today's most interesting samples rarely make our jobs easy for us. Unfortunately many of the systems that we want to study crystallise as very tiny crystals. This can be particularly true of pharmaceuticals but is a widespread difficulty in many areas of chemistry and materials where we repeatedly face these challenges. Constant pressure to deliver high quality results and extract as much information as possible are coupled with pressures to do so both cost and time efficiently. The combination of the Rigaku MicroMax 007HF generator with the RAPID II unique curved, large area image plate detector already provides a hugely flexible tool to address many of these challenges. Advances in optics now mean that this powerful combination of generator and detector can be used with both Mo and Cu radiation (or Cu and Cr) on the same instrument, just by swapping the rapidly interchangeable targets. The image plate is highly sensitive for all these wavelengths providing for high quality data without compromise. The extremely large active area of the detector (-60 to 144°) allows a massive solid angle of data to be collected in a single exposure; ideal for fast high resolution Cu data for absolute configuration determination and equally for very high resolution data with Mo radiation. The exceptional low noise and wide dynamic range also suit the long exposure times often necessary for very tiny crystals -even with a brilliant source -without saturation or excessive noise problems. This single instrument is so versatile that it can replace several others -for single crystal diffraction studies (both small and macromolecular) at both wavelengths as well as powder diffraction. Results of studies using this new dual wavelength capability system will be presented.
Understanding the impact of the counterion on the properties of an acidic or basic drug may inf... more 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. 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. 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. 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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