Solvent diversity in polymorph screening

被引:46
作者
Alleso, Morten [1 ]
Van Den Berg, Frans [2 ]
Cornett, Claus [1 ]
Jorgensen, Flemming Steen [3 ]
Halling-Sorensen, Bent [1 ]
De Diego, Heidi Lopez [4 ]
Hovgaard, Lars [1 ]
Aaltonen, Jaakko [5 ]
Rantanen, Jukka [1 ]
机构
[1] Univ Copenhagen, Fac Pharmaceut Sci, Dept Pharmaceut & Analyt Chem, DK-2100 Copenhagen, Denmark
[2] Univ Copenhagen, Fac Life Sci, Dept Food Sci, Frederiksberg C, Denmark
[3] Univ Copenhagen, Fac Pharmaceut Sci, Dept Med Chem, DK-2100 Copenhagen, Denmark
[4] H Lundbeck & Co AS, Analyt R&D, Valby, Denmark
[5] Univ Helsinki, Fac Pharm, Div Pharmaceut Technol, Helsinki, Finland
关键词
solvent; solid state; polymorphism; polymorph screening; crystallization; toxicity; physicochemical descriptors; molecular interaction fields; principal component analysis (PCA); self-organizing maps (SOMs);
D O I
10.1002/jps.21153
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Selecting a diverse set of solvents to be included in polymorph screening assignments can be a challenging task. As an aid to decision making, a database of 218 organic solvents with 24 property descriptors was explored and visualized using multivariate tools. The descriptors included, among others, logP, vapor pressure, hydrogen bond formation capabilities, polarity, number of pi-bonds and descriptors derived from molecular interaction field calculations (e.g., size/shape parameters and hydrophilic/hydrophobic regions). The data matrix was initially analyzed using principal component analysis (PCA). Results from the PCA showed 57% cumulative variance being explained in the first two principal components (PCs), although relevant information was also found in the third, fourth and fifth component, revealing distinct clusters of solvents. Since five dimensions were not suitable for visual presentation, a nonlinear method, self-organizing maps (SOMs), was applied to the dataset. The constructed SOM displayed features of clusters observed in the first three PCs, however in a more compelling way. Thus, the SOM was chosen as the visually most convenient way to display the diversity of the 218 solvents. In addition, it was demonstrated how safety aspects can be considered by labeling a large fraction of the solvents in the SOM with toxicological information. (C) 2007 Wiley-Liss, Inc. and the American Pharmacists Association.
引用
收藏
页码:2145 / 2159
页数:15
相关论文
共 45 条
[1]  
[Anonymous], POLYMORP PHARM IND, DOI [10.1002/3527607889.ch11, DOI 10.1002/3527607889.CH11]
[2]   SCREENING OF SUITABLE SOLVENTS IN ORGANIC-SYNTHESIS - STRATEGIES FOR SOLVENT SELECTION [J].
CARLSON, R ;
LUNDSTEDT, T ;
ALBANO, C .
ACTA CHEMICA SCANDINAVICA SERIES B-ORGANIC CHEMISTRY AND BIOCHEMISTRY, 1985, 39 (02) :79-91
[3]   APPROACH TO A GENERAL CLASSIFICATION OF SOLVENTS USING A MULTIVARIATE STATISTICAL TREATMENT OF QUANTITATIVE SOLVENT PARAMETERS [J].
CHASTRETTE, M ;
RAJZMANN, M ;
CHANON, M ;
PURCELL, KF .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1985, 107 (01) :1-11
[4]   Dealing with the impact of ritonavir polymorphs on the late stages of bulk drug process development [J].
Chemburkar, SR ;
Bauer, J ;
Deming, K ;
Spiwek, H ;
Patel, K ;
Morris, J ;
Henry, R ;
Spanton, S ;
Dziki, W ;
Porter, W ;
Quick, J ;
Bauer, P ;
Donaubauer, J ;
Narayanan, BA ;
Soldani, M ;
Riley, D ;
McFarland, K .
ORGANIC PROCESS RESEARCH & DEVELOPMENT, 2000, 4 (05) :413-417
[5]   A whole output strategy for polymorph screening: Combining crystal structure prediction, graph set analysis, and targeted crystallization experiments in the case of diflunisal [J].
Cross, WI ;
Blagden, N ;
Davey, RJ ;
Pritchard, RG ;
Neumann, MA ;
Roberts, RJ ;
Rowe, RC .
CRYSTAL GROWTH & DESIGN, 2003, 3 (02) :151-158
[6]   Molecular fields in quantitative structure-permeation relationships: the VolSurf approach [J].
Cruciani, C ;
Crivori, P ;
Carrupt, PA ;
Testa, B .
JOURNAL OF MOLECULAR STRUCTURE-THEOCHEM, 2000, 503 (1-2) :17-30
[7]   VolSurf: a new tool for the pharmacokinetic optimization of lead compounds [J].
Cruciani, G ;
Pastor, M ;
Guba, W .
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES, 2000, 11 :S29-S39
[8]   Crystal structures of drugs: Advances in determination, prediction and engineering [J].
Datta, S ;
Grant, DJW .
NATURE REVIEWS DRUG DISCOVERY, 2004, 3 (01) :42-57
[9]   Crystallization - How come you look so good? [J].
Davey, RJ .
NATURE, 2004, 428 (6981) :374-375
[10]   DISAPPEARING POLYMORPHS [J].
DUNITZ, JD ;
BERNSTEIN, J .
ACCOUNTS OF CHEMICAL RESEARCH, 1995, 28 (04) :193-200