Structure, solubility, screening, and synthesis of molecular salts

@article{citeulike:3039327, abstract = {The preparation of molecular salts as potential delivery vehicles for pharmaceutically active compounds is more common than current appreciation of the phenomena governing the solubility and isolation of salts suggests. In addition, it would appear that there are no reported measurements on a large enough data set for a serious structure-property relationship analysis to have been performed for this class of material. This means that at present, the ability to predict which salt forms will have desirable physical properties is essentially nonexistent. The work reported here sets out to explore these issues using new data on 17 salts obtained from a screen performed on the basic pharmaceutical ephedrine. The importance of solvent choice in salt formation, of salt selection in the control of bioavailability and of ternary phase equilibria in salt isolation and the relationship between a number of measured and calculated crystal properties are illustrated and discussed. The consequences of these relations for the general design, implementation, interpretation, and scale-up of salts screens are also explored. {\copyright} 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 96: 1053-1068, 2007}, address = {Process Engineering Group, PR\&D, AstraZeneca, Macclesfield, Cheshire, SK10 2NA, United Kingdom; Molecular Materials Centre, School of Chemical Engineering and Analytical Science, The University of Manchester, Manchester, M60 1QD, United Kingdom; Preformulation \& Biopharmaceutics, PAR\&D, AstraZeneca, Macclesfield, Cheshire, SK10 2NA, United Kingdom}, author = {Black, Simon N. and Collier, Edwin A. and Davey, Roger J. and Roberts, Ron J. }, citeulike-article-id = {3039327}, doi = {http://dx.doi.org/10.1002/jps.20927}, journal = {Journal of Pharmaceutical Sciences}, number = {5}, pages = {1053--1068}, posted-at = {2008-07-24 13:01:35}, priority = {0}, title = {Structure, solubility, screening, and synthesis of molecular salts}, url = {http://dx.doi.org/10.1002/jps.20927}, volume = {96}, year = {2007} }

TY - JOUR ID - citeulike:3039327 L3 - citeulike-article-id:3039327 TI - Structure, solubility, screening, and synthesis of molecular salts JF - Journal of Pharmaceutical Sciences VL - 96 IS - 5 SP - 1053 EP - 1068 AD - Process Engineering Group, PR&D, AstraZeneca, Macclesfield, Cheshire, SK10 2NA, United Kingdom; Molecular Materials Centre, School of Chemical Engineering and Analytical Science, The University of Manchester, Manchester, M60 1QD, United Kingdom; Preformulation & Biopharmaceutics, PAR&D, AstraZeneca, Macclesfield, Cheshire, SK10 2NA, United Kingdom N2 - The preparation of molecular salts as potential delivery vehicles for pharmaceutically active compounds is more common than current appreciation of the phenomena governing the solubility and isolation of salts suggests. In addition, it would appear that there are no reported measurements on a large enough data set for a serious structure-property relationship analysis to have been performed for this class of material. This means that at present, the ability to predict which salt forms will have desirable physical properties is essentially nonexistent. The work reported here sets out to explore these issues using new data on 17 salts obtained from a screen performed on the basic pharmaceutical ephedrine. The importance of solvent choice in salt formation, of salt selection in the control of bioavailability and of ternary phase equilibria in salt isolation and the relationship between a number of measured and calculated crystal properties are illustrated and discussed. The consequences of these relations for the general design, implementation, interpretation, and scale-up of salts screens are also explored. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 96: 1053-1068, 2007 AU - Black, Simon AU - Collier, Edwin AU - Davey, Roger AU - Roberts, Ron PY - 2007/// UR - http://dx.doi.org/10.1002/jps.20927 ER -