Cocrystallization by Freeze-Drying: Preparation of Novel Multicomponent Crystal Forms

We demonstrate the utility of freeze-drying as a general method for cocrystal synthesis as well as for the preparation of new solid forms of drug–coformer cocrystal systems. Using this approach, several previously reported cocrystal phases containing pharmaceutical compounds were reproduced. In addition, a novel solid solution of caffeine and theophylline and a potential new crystal form of the theophylline:oxalic acid cocrystal were prepared. It is shown that cocrystal formation proceeds via an amorphous phase that is generated as solvent sublimes during the freeze-drying process. The application of freeze-drying to cocrystallization is advantageous as it avoids problems caused by differences in the solubilities of coformers and is a technique that is widely used to prepare products on an industrial scale, such as in the manufacture of pharmaceutical dosage forms.

[1]  W. Jones,et al.  Mechanochemistry and co-crystal formation: effect of solvent on reaction kinetics. , 2002, Chemical communications.

[2]  William Jones,et al.  Pharmaceutical Cocrystallization: Engineering a Remedy for Caffeine Hydration , 2005 .

[3]  M. Alderton,et al.  Distributed multipole analysis , 2006 .

[4]  Bing-Shiou Yang,et al.  A Practical Solid Form Screen Approach To Identify a Pharmaceutical Glutaric Acid Cocrystal for Development , 2009 .

[5]  G. Enright,et al.  The Structure of Two Anhydrous Polymorphs of Caffeine from Single-Crystal Diffraction and Ultrahigh-Field Solid-State 13C NMR Spectroscopy , 2007 .

[6]  Naír Rodríguez-Hornedo,et al.  Cocrystal Formation during Cogrinding and Storage is Mediated by Amorphous Phase , 2006, Pharmaceutical Research.

[7]  J. McMahon,et al.  Crystal engineering of the composition of pharmaceutical phases. , 2003, Chemical communications.

[8]  A. Bond,et al.  Use of in situ atomic force microscopy to follow phase changes at crystal surfaces in real time. , 2013, Angewandte Chemie.

[9]  Sitaram P. Velaga,et al.  Formation of Cocrystals from Stoichiometric Solutions of Incongruently Saturating Systems by Spray Drying , 2010 .

[10]  W. Motherwell,et al.  Physical stability enhancement of theophylline via cocrystallization. , 2006, International journal of pharmaceutics.

[11]  Geoff G. Z. Zhang,et al.  Efficient co-crystal screening using solution-mediated phase transformation. , 2007, Journal of pharmaceutical sciences.

[12]  M. Caira.  Molecular complexes of sulfonamides. 2.1:1 complexes between drug molecules: sulfadimidine-acetylsalicylic acid and sulfadimidine-4-aminosalicylic acid , 1992 .

[13]  M. Eddleston,et al.  Screening for polymorphs of cocrystals: a case study , 2013 .

[14]  V. Caron,et al.  Transformation of pharmaceutical compounds upon milling and comilling: the role of T(g). , 2007, Journal of pharmaceutical sciences.

[15]  M. Eddleston,et al.  Cocrystal dissociation and molecular demixing in the solid state. , 2012, Chemical communications.

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

[17]  B. Delley.  From molecules to solids with the DMol3 approach , 2000 .

[18]  J. Anwar,et al.  Collective displacements in a molecular crystal polymorphic transformation , 2013 .

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

[20]  T. Friščić,et al.  Screening for inclusion compounds and systematic construction of three-component solids by liquid-assisted grinding. , 2006, Angewandte Chemie.

[21]  William Jones,et al.  Improving Mechanical Properties of Crystalline Solids by Cocrystal Formation: New Compressible Forms of Paracetamol , 2009 .

[22]  J. Klinowski,et al.  Crystal engineering using co-crystallisation of phenazine with dicarboxylic acids , 2000 .

[23]  .. A.M.Galal.  Use of Polymerase Chain Reaction for Detecting Banana Bunchy Top Nanovirus , 2007 .

[24]  Michael J. Zaworotko,et al.  Crystal engineering of the composition of pharmaceutical phases. Do pharmaceutical co-crystals represent a new path to improved medicines? , 2004 .

[25]  Donald E. Williams,et al.  Improved intermolecular force field for molecules containing H, C, N, and O atoms, with application to nucleoside and peptide crystals , 2001, J. Comput. Chem..

[26]  K. Nagapudi,et al.  Manufacture of pharmaceutical co-crystals using twin screw extrusion: a solvent-less and scalable process. , 2010, Journal of pharmaceutical sciences.

[27]  V. Caron,et al.  Transformations of crystalline sugars upon milling , 2007 .

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

[29]  N. Rodríguez-Hornedo,et al.  Pharmaceutical cocrystals and poorly soluble drugs. , 2013, International journal of pharmaceutics.

[30]  A. Cesàro,et al.  Thermodynamic properties of caffeine crystal forms , 1980 .

[31]  G. P. Stahly,et al.  A Survey of Cocrystals Reported Prior to 2000 , 2009 .

[32]  S. Yalkowsky,et al.  Use of pure t-butanol as a solvent for freeze-drying: a case study. , 2001, International journal of pharmaceutics.

[33]  P. Bag,et al.  A kinetically controlled crystallization process for identifying new co-crystal forms: fast evaporation of solvent from solutions to dryness , 2011 .

[34]  Ann Thayer,et al.  FORM AND FUNCTION , 2007 .

[35]  B. Delley.  An all‐electron numerical method for solving the local density functional for polyatomic molecules , 1990 .

[36]  Peddy Vishweshwar,et al.  The predictably elusive form II of aspirin. , 2005, Journal of the American Chemical Society.

[37]  Donald E. Williams.  Improved intermolecular force field for crystalline oxohydrocarbons including OHO hydrogen bonding , 2001 .

[38]  Raj Suryanarayanan,et al.  A rapid thermal method for cocrystal screening , 2008 .

[39]  Ahmad Y. Sheikh,et al.  Scalable solution cocrystallization: case of carbamazepine-nicotinamide I , 2009 .

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

[41]  K. Cheng,et al.  Lateral distribution of cholesterol in dioleoylphosphatidylcholine lipid bilayers: cholesterol-phospholipid interactions at high cholesterol limit. , 2004, Biophysical journal.

[42]  Margaret C. Etter,et al.  Hydrogen bonds as design elements in organic chemistry , 1991 .

[43]  James A. Chisholm,et al.  COMPACK: a program for identifying crystal structure similarity using distances , 2005 .

[44]  A. Matzger,et al.  Polymorphism in Carbamazepine Cocrystals. , 2008, Crystal growth & design.

[45]  Constantinos C. Pantelides,et al.  Ab initio crystal structure prediction—I. Rigid molecules , 2005, J. Comput. Chem..

[46]  J. Andrieu,et al.  Sublimation kinetics and sublimation end-point times during freeze-drying of pharmaceutical active principle with organic co-solvent formulations , 2009 .

[47]  Orn Almarsson,et al.  Crystal engineering of novel cocrystals of a triazole drug with 1,4-dicarboxylic acids. , 2003, Journal of the American Chemical Society.

[48]  W. Kauzmann.  The Nature of the Glassy State and the Behavior of Liquids at Low Temperatures. , 1948 .

[49]  L Yu,et al.  Amorphous pharmaceutical solids: preparation, characterization and stabilization. , 2001, Advanced drug delivery reviews.

[50]  Orn Almarsson,et al.  Performance comparison of a co-crystal of carbamazepine with marketed product. , 2007, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[51]  R. Davey,et al.  Making Co-crystals-The utility of ternary phase diagrams , 2007 .

[52]  L. Fábián,et al.  Powder X-ray diffraction as an emerging method to structurally characterize organic solids. , 2007, Organic letters.

[53]  J. Beijnen,et al.  Pharmaceutical development of a lyophilised dosage form for the investigational anticancer agent Imexon using dimethyl sulfoxide as solubilising and stabilising agent. , 2005, Journal of pharmaceutical sciences.

[54]  J. McMahon,et al.  Crystal engineering of pharmaceutical co-crystals from polymorphic active pharmaceutical ingredients. , 2005, Chemical communications.

[55]  Sarah J. Nehm,et al.  Reaction crystallization of pharmaceutical molecular complexes. , 2006, Molecular pharmaceutics.

[56]  Geoff G. Z. Zhang,et al.  A "hidden" co-crystal of caffeine and adipic acid. , 2007, Chemical communications.

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

[58]  M. Descamps,et al.  Plastic and glassy crystal states of caffeine. , 2005, The journal of physical chemistry. B.