Can computed crystal energy landscapes help understand pharmaceutical solids?

Computational crystal structure prediction (CSP) methods can now be applied to the smaller pharmaceutical molecules currently in drug development. We review the recent uses of computed crystal energy landscapes for pharmaceuticals, concentrating on examples where they have been used in collaboration with industrial-style experimental solid form screening. There is a strong complementarity in aiding experiment to find and characterise practically important solid forms and understanding the nature of the solid form landscape.

[1]  Claire S. Adjiman,et al.  Towards crystal structure prediction of complex organic compounds – a report on the fifth blind test , 2011, Acta crystallographica. Section B, Structural science.

[2]  J. Bernstein,et al.  Disappearing Polymorphs Revisited , 2015, Angewandte Chemie.

[3]  Raymond E. Davis,et al.  Patterns in Hydrogen Bonding: Functionality and Graph Set Analysis in Crystals , 1995 .

[4]  G. P. Stahly.  Diversity in Single- and Multiple-Component Crystals. The Search for and Prevalence of Polymorphs and Cocrystals , 2007 .

[5]  J. Bernstein,et al.  Facts and fictions about polymorphism. , 2015, Chemical Society reviews.

[6]  S. Price.  Why don't we find more polymorphs? , 2013, Acta crystallographica Section B, Structural science, crystal engineering and materials.

[7]  P. W. Cains,et al.  Sonocrystallization: The Use of Ultrasound for Improved Industrial Crystallization , 2005 .

[8]  Michael J. Cima,et al.  Elucidation of crystal form diversity of the HIV protease inhibitor ritonavir by high-throughput crystallization , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[9]  J. Dunitz.  Are crystal structures predictable? , 2003, Chemical communications.

[10]  M. Messerschmidt,et al.  Charge density of (-)-strychnine from 100 to 15 K, a comparison of four data sets. , 2005, Acta Crystallographica Section B Structural Science.

[11]  G. Day,et al.  Predicting inclusion behaviour and framework structures in organic crystals. , 2009, Chemistry.

[12]  C. Adjiman,et al.  Efficient Handling of Molecular Flexibility in Ab Initio Generation of Crystal Structures. , 2015, Journal of chemical theory and computation.

[13]  Naír Rodríguez-Hornedo,et al.  Analysis of 50 Crystal Structures Containing Carbamazepine Using the Materials Module of Mercury CSD , 2009 .

[14]  A. Matzger,et al.  Crystalline polymorph selection and discovery with polymer heteronuclei. , 2005, Journal of the American Chemical Society.

[15]  G. Day,et al.  Importance of Molecular Shape for the Overall Stability of Hydrogen Bond Motifs in the Crystal Structures of Various Carbamazepine-Type Drug Molecules , 2007 .

[16]  R. K. Jetti,et al.  New solvates of an old drug compound (phenobarbital): structure and stability. , 2014, The journal of physical chemistry. B.

[17]  Peter T. A. Galek,et al.  Knowledge-based model of hydrogen-bonding propensity in organic crystals. , 2007, Acta crystallographica. Section B, Structural science.

[18]  Sarah L Price,et al.  Predicting crystal structures of organic compounds. , 2014, Chemical Society reviews.

[19]  Jerome G. P. Wicker,et al.  Will it crystallise? Predicting crystallinity of molecular materials , 2015 .

[20]  T. Gelbrich,et al.  Solid state characterisation of four solvates of R-cinacalcet hydrochloride , 2008 .

[21]  A. Matzger,et al.  Nonamorphism in flufenamic acid and a new record for a polymorphic compound with solved structures. , 2012, Journal of the American Chemical Society.

[22]  D. Fox.  Physics and Chemistry of the Organic Solid State , 1963 .

[23]  G. Stephenson,et al.  Crystal Structure Prediction of a Flexible Molecule of Pharmaceutical Interest with Unusual Polymorphic Behavior , 2013 .

[24]  G. Day,et al.  Determination of the crystal structure of a new polymorph of theophylline. , 2013, Chemistry.

[25]  Sarah L Price,et al.  Successful prediction of a model pharmaceutical in the fifth blind test of crystal structure prediction. , 2011, International journal of pharmaceutics.

[26]  O. Grassmann,et al.  Combined crystal structure prediction and high-pressure crystallization in rational pharmaceutical polymorph screening , 2015, Nature Communications.

[27]  Adam J. Matzger,et al.  Towards Exhaustive and Automated High-Throughput Screening for Crystalline Polymorphs , 2014, ACS combinatorial science.

[28]  G. Day,et al.  De novo determination of the crystal structure of a large drug molecule by crystal structure prediction-based powder NMR crystallography. , 2013, Journal of the American Chemical Society.

[29]  Cheryl L. Doherty,et al.  The integration of solid‐form informatics into solid‐form selection , 2015, The Journal of pharmacy and pharmacology.

[30]  Jonathan Brown,et al.  Enhancement of oral bioavailability of an HIV-attachment inhibitor by nanosizing and amorphous formulation approaches. , 2009, International journal of pharmaceutics.

[31]  M. D. King,et al.  Prediction of the Unknown Crystal Structure of Creatine Using Fully Quantum Mechanical Methods , 2011 .

[32]  A. West,et al.  Crystal structure determination by combined synchrotron powder X-ray diffraction and crystal structure prediction: 1 : 1 L-ephedrine D-tartrate , 2013 .

[33]  A. Seidel-Morgenstern,et al.  Are the Crystal Structures of Enantiopure and Racemic Mandelic Acids Determined by Kinetics or Thermodynamics? , 2015, Journal of the American Chemical Society.

[34]  Volker Kahlenberg,et al.  Crystallization of Metastable Polymorphs of Phenobarbital by Isomorphic Seeding , 2009 .

[35]  C. Adjiman,et al.  Prediction of the crystal structures of axitinib, a polymorphic pharmaceutical molecule , 2015 .

[36]  Lian Yu.  Polymorphism in molecular solids: an extraordinary system of red, orange, and yellow crystals. , 2010, Accounts of chemical research.

[37]  In Sung Lee,et al.  Crystallization on confined engineered surfaces: a method to control crystal size and generate different polymorphs. , 2005, Journal of the American Chemical Society.

[38]  M. Habgood.  Form II Caffeine: A Case Study for Confirming and Predicting Disorder in Organic Crystals , 2011 .

[39]  G. Beran.  Modeling Polymorphic Molecular Crystals with Electronic Structure Theory. , 2016, Chemical reviews.

[40]  Kyle L. Morris,et al.  The delicate balance between gelation and crystallisation: structural and computational investigations , 2010 .

[41]  Tejender S. Thakur,et al.  Crystal structure and prediction. , 2015, Annual review of physical chemistry.

[42]  A. Gavezzotti,et al.  Are racemic crystals favored over homochiral crystals by higher stability or by kinetics? Insights from comparative studies of crystalline stereoisomers. , 2014, The Journal of organic chemistry.

[43]  S. Price,et al.  Computed crystal energy landscapes for understanding and predicting organic crystal structures and polymorphism. , 2009, Accounts of chemical research.

[44]  P. Karamertzanis,et al.  Which, if any, hydrates will crystallise? Predicting hydrate formation of two dihydroxybenzoic acids. , 2011, Chemical communications.

[45]  J. McMahon,et al.  Contrasting Polymorphism of Related Small Molecule Drugs Correlated and Guided by the Computed Crystal Energy Landscape , 2014 .

[46]  Michael B. Hursthouse,et al.  Over one hundred solvates of sulfathiazole , 2001 .

[47]  J. McMahon,et al.  Navigating the Waters of Unconventional Crystalline Hydrates , 2015, Molecular pharmaceutics.

[48]  C. Adjiman,et al.  General computational algorithms for ab initio crystal structure prediction for organic molecules. , 2014, Topics in current chemistry.

[49]  P. Mörschel,et al.  Structure determination from powder data without prior indexing, using a similarity measure based on cross-correlation functions. , 2014, Acta crystallographica Section B, Structural science, crystal engineering and materials.

[50]  K. Morris,et al.  Structural Properties, Order–Disorder Phenomena, and Phase Stability of Orotic Acid Crystal Forms , 2016, Molecular pharmaceutics.

[51]  Andreas Seidel-Morgenstern,et al.  Processes to separate enantiomers. , 2014, Angewandte Chemie.

[52]  K. Fromm,et al.  Proceedings of the Chemical Society. February 1961 , 1961 .

[53]  Lian Yu,et al.  Molecular basis for the stability relationships between homochiral and racemic crystals of tazofelone: a spectroscopic, crystallographic, and thermodynamic investigation , 2000 .

[54]  Keith R Horspool,et al.  Development of a targeted polymorph screening approach for a complex polymorphic and highly solvating API. , 2010, Journal of pharmaceutical sciences.

[55]  Yuriy A. Abramov,et al.  Current Computational Approaches to Support Pharmaceutical Solid Form Selection , 2013 .

[56]  A. Newman.  Specialized Solid Form Screening Techniques , 2013 .

[57]  C. Adjiman,et al.  The polymorphs of ROY: application of a systematic crystal structure prediction technique. , 2012, Acta crystallographica. Section B, Structural science.

[58]  T. Threlfall,et al.  Why Do Organic Compounds Crystallise Well or Badly or Ever so Slowly? Why Is Crystallisation Nevertheless Such a Good Purification Technique?† , 2009 .

[59]  Alfred Y Lee,et al.  Crystal polymorphism in chemical process development. , 2011, Annual review of chemical and biomolecular engineering.

[60]  Claude Didierjean,et al.  Crystallization of proteins under an external electric field , 1999 .

[61]  Ranjit Thakuria,et al.  Polymorphic form IV of olanzapine. , 2011, Acta crystallographica. Section C, Crystal structure communications.

[62]  Gary J. Miller,et al.  Structure and stability of two polymorphs of creatine and its monohydrate , 2014 .

[63]  A. Gavezzotti,et al.  Are Crystal Structures Predictable , 1994 .

[64]  U. Griesser,et al.  Creatine: Polymorphs Predicted and Found , 2014, Crystal growth & design.

[65]  Graeme M. Day,et al.  Current approaches to predicting molecular organic crystal structures , 2011 .

[66]  René Holm,et al.  The solid‐state continuum: a perspective on the interrelationships between different solid‐state forms in drug substance and drug product , 2015, The Journal of pharmacy and pharmacology.

[67]  M. Habgood,et al.  The Amorphous Form of Salicylsalicylic Acid: Experimental Characterization and Computational Predictability , 2013 .

[68]  Michael B Hursthouse,et al.  Structural systematics of 4,4'-disubstituted benzenesulfonamidobenzenes. 1. Overview and dimer-based isostructures. , 2007, Acta crystallographica. Section B, Structural science.

[69]  G. Beran,et al.  Fragment-based (13)C nuclear magnetic resonance chemical shift predictions in molecular crystals: An alternative to planewave methods. , 2015, The Journal of chemical physics.

[70]  Sarah L Price,et al.  Modelling organic crystal structures using distributed multipole and polarizability-based model intermolecular potentials. , 2010, Physical chemistry chemical physics : PCCP.

[71]  J. McMahon,et al.  A molecular picture of the problems in ensuring structural purity of tazofelone , 2014 .

[72]  E. Salager,et al.  Powder crystallography by combined crystal structure prediction and high-resolution 1H solid-state NMR spectroscopy. , 2010, Journal of the American Chemical Society.

[73]  G. Day,et al.  A strategy for predicting the crystal structures of flexible molecules: the polymorphism of phenobarbital. , 2007, Physical chemistry chemical physics : PCCP.

[74]  T. Gelbrich,et al.  Specific energy contributions from competing hydrogen-bonded structures in six polymorphs of phenobarbital , 2016, Chemistry Central Journal.

[75]  P Verwer,et al.  A test of crystal structure prediction of small organic molecules. , 2000, Acta crystallographica. Section B, Structural science.

[76]  M. Schmidt,et al.  Determination of the structure of the violet pigment C22H12Cl2N6O4 from a non-indexed X-ray powder diagram. , 2005, Acta Crystallographica Section B Structural Science.

[77]  Graeme M. Day,et al.  Which conformations make stable crystal structures? Mapping crystalline molecular geometries to the conformational energy landscape , 2014 .

[78]  T. C. Lewis,et al.  The observed and energetically feasible crystal structures of 5-substituted uracils , 2008 .

[79]  A. Ikni,et al.  Experimental Demonstration of the Carbamazepine Crystallization from Non-photochemical Laser-Induced Nucleation in Acetonitrile and Methanol , 2014 .

[80]  O. Almarsson,et al.  Molecules, Materials, Medicines (M3): Linking Molecules to Medicines through Pharmaceutical Material Science , 2015 .

[81]  Iain D. H. Oswald,et al.  Exploring the Experimental and Computed Crystal Energy Landscape of Olanzapine , 2013 .

[82]  S. Price,et al.  A strategy for producing predicted polymorphs: catemeric carbamazepine form V. , 2011, Chemical communications.

[83]  S. Chemburkar,et al.  Dealing with the Impact of Ritonavir Polymorphs on the Late Stages of Bulk Drug Process Development , 2000 .

[84]  Tejender S. Thakur,et al.  New crystalline salt forms of levofloxacin: conformational analysis and attempts towards the crystal structure prediction of the anhydrous form , 2014 .

[85]  Marc-Antoine Perrin,et al.  Energy ranking of molecular crystals using density functional theory calculations and an empirical van der waals correction. , 2005, The journal of physical chemistry. B.

[86]  A. Myerson,et al.  Supersaturation and Polarization Dependence of Polymorph Control in the Nonphotochemical Laser-Induced Nucleation (NPLIN) of Aqueous Glycine Solutions , 2006 .

[87]  J. Deadman,et al.  The unexpected but predictable tetrazole packing in flexible 1-benzyl-1H-tetrazole , 2012 .

[88]  H. Oberacher,et al.  4-Aminoquinaldine monohydrate polymorphism: Prediction and impurity aided discovery of a difficult to access stable form. , 2016, CrystEngComm.

[89]  Michael B. Hursthouse,et al.  A versatile procedure for the identification, description and quantification of structural similarity in molecular crystals , 2005 .

[90]  J. Rantanen,et al.  The Future of Pharmaceutical Manufacturing Sciences , 2015, Journal of pharmaceutical sciences.

[91]  O. Rascol,et al.  Rotigotine transdermal patch for the treatment of Parkinson’s Disease , 2013, Fundamental & clinical pharmacology.

[92]  Lian Yu,et al.  Discovery of a solid solution of enantiomers in a racemate-forming system by seeding. , 2006, Journal of the American Chemical Society.

[93]  Robin Taylor,et al.  Mercury: visualization and analysis of crystal structures , 2006 .

[94]  Geoff G. Z. Zhang,et al.  The curious case of (caffeine)·(benzoic acid): how heteronuclear seeding allowed the formation of an elusive cocrystal , 2013 .

[95]  S. Price,et al.  Evaluating a Crystal Energy Landscape in the Context of Industrial Polymorph Screening , 2013 .

[96]  G. Day,et al.  Polymorph identification and crystal structure determination by a combined crystal structure prediction and transmission electron microscopy approach. , 2013, Chemistry.

[97]  T. Gelbrich,et al.  Solid state forms of 4-aminoquinaldine - From void structures with and without solvent inclusion to close packing. , 2015, CrystEngComm.

[98]  Blair F. Johnston,et al.  A random forest model for predicting the crystallisability of organic molecules , 2015 .

[99]  J. Bauer,et al.  Ritonavir: An Extraordinary Example of Conformational Polymorphism , 2001, Pharmaceutical Research.

[100]  K. Fromm,et al.  Polymorphism, what it is and how to identify it: a systematic review , 2013 .

[101]  S. Price,et al.  Is the Fenamate Group a Polymorphophore? Contrasting the Crystal Energy Landscapes of Fenamic and Tolfenamic Acids , 2012 .

[102]  C. Morrison,et al.  Assessing the performance of density functional theory in optimizing molecular crystal structure parameters. , 2014, Acta crystallographica Section B, Structural science, crystal engineering and materials.

[103]  Å. Rasmuson,et al.  Influence of History of Solution in Crystal Nucleation of Fenoxycarb: Kinetics and Mechanisms , 2014 .

[104]  A. Tkatchenko,et al.  Many-body van der Waals interactions in molecules and condensed matter , 2014, Journal of physics. Condensed matter : an Institute of Physics journal.