Lattice energy calculation – A quick tool for screening of cocrystals and estimation of relative solubility. Case of flavonoids

Abstract Cocrystals (or multicomponent crystals) have physico-chemical properties that are different from crystals of pure components. This is significant in drug development, since the desired properties, e.g. solubility, stability and bioavailability, can be tailored by binding two substances into a single crystal without chemical modification of an active component. Here, the F lexcryst program suite, implemented with a data mining force field, was used to estimate the relative stability and, consequently, the relative solubility of cocrystals of flavonoids vs their pure crystals, stored in the Cambridge Structural Database. The considerable potency of this approach for in silico screening of cocrystals, as well as their relative solubility, was demonstrated.

[1]  C. C. Seaton,et al.  Applying Hot-Stage Microscopy to Co-Crystal Screening: A Study of Nicotinamide with Seven Active Pharmaceutical Ingredients , 2008 .

[2]  W. L. Jorgensen,et al.  Prediction of Properties from Simulations: Free Energies of Solvation in Hexadecane, Octanol, and Water , 2000 .

[3]  D. Hofmann,et al.  Cluster analysis and completeness of crystal structure generation , 2009 .

[4]  Joannis Apostolakis,et al.  Crystal structure prediction by data mining , 2003 .

[5]  Michael J Cima,et al.  High-throughput crystallization: polymorphs, salts, co-crystals and solvates of pharmaceutical solids. , 2004, Advanced drug delivery reviews.

[6]  Tejender S. Thakur,et al.  Significant progress in predicting the crystal structures of small organic molecules--a report on the fourth blind test. , 2009, Acta crystallographica. Section B, Structural science.

[7]  K. Terada,et al.  Cocrystal Screening of Stanolone and Mestanolone Using Slurry Crystallization , 2008 .

[8]  Shunzhou Wan,et al.  Calculation of the aqueous solvation energy and entropy, as well as free energy, of simple polar solutes. , 2004, The Journal of chemical physics.

[9]  G. Desiraju,et al.  Supramolecular Synthons and Pattern Recognition , 1998 .

[10]  D. Hofmann,et al.  Solvent and Isotopic Effects on Acridine and Deuterated Acridine Polymorphism , 2012 .

[11]  B. Shekunov,et al.  CRYSTALLIZATION PROCESSES IN PHARMACEUTICAL TECHNOLOGY AND DRUG DELIVERY DESIGN , 2000 .

[12]  N. Rodríguez-Hornedo.  Cocrystals: Molecular design of pharmaceutical materials , 2007 .

[13]  Michael J Zaworotko,et al.  Cocrystals of quercetin with improved solubility and oral bioavailability. , 2011, Molecular pharmaceutics.

[14]  William Jones,et al.  Recent Advances in Understanding the Mechanism of Cocrystal Formation via Grinding , 2009 .

[15]  Sarah L Price,et al.  Can the Formation of Pharmaceutical Cocrystals Be Computationally Predicted? 2. Crystal Structure Prediction. , 2009, Journal of chemical theory and computation.

[16]  W L Jorgensen,et al.  Prediction of drug solubility from Monte Carlo simulations. , 2000, Bioorganic & medicinal chemistry letters.

[17]  Oleg A. Raevsky,et al.  Sublimation of Molecular Crystals: Prediction of Sublimation Functions on the Basis of HYBOT Physicochemical Descriptors and Structural Clusterization , 2010 .

[18]  F. J. Luque,et al.  Theoretical Methods for the Description of the Solvent Effect in Biomolecular Systems. , 2000, Chemical reviews.

[19]  Thomas Lengauer,et al.  Derivation of a scoring function for crystal structure prediction. , 2001, Acta crystallographica. Section A, Foundations of crystallography.

[20]  P. Karamertzanis,et al.  Can the Formation of Pharmaceutical Cocrystals Be Computationally Predicted? I. Comparison of Lattice Energies , 2009 .

[21]  A. Newman,et al.  Pharmaceutical Cocrystals and Their Physicochemical Properties , 2009, Crystal growth & design.

[22]  Christer B. Aakeröy,et al.  Building co-crystals with molecular sense and supramolecular sensibility , 2005 .

[23]  Christopher A. Hunter,et al.  Virtual cocrystal screening , 2011 .

[24]  D. J. Timmons,et al.  Assembling Extended Structures with Flavonoids , 2008 .

[25]  Peddy Vishweshwar,et al.  Pharmaceutical co-crystals. , 2006, Journal of pharmaceutical sciences.

[26]  Aatto Laaksonen,et al.  Determination of solvation free energies by adaptive expanded ensemble molecular dynamics. , 2004, The Journal of chemical physics.

[27]  New force field for molecular simulation and crystal design developed based on the “data mining” method , 2005 .

[28]  Ashwini Nangia,et al.  Solubility Advantage of Amorphous Drugs and Pharmaceutical Cocrystals , 2011 .