Improving Mechanical Properties of Crystalline Solids by Cocrystal Formation: New Compressible Forms of Paracetamol

Poor mechanical properties of paracetamol are improved through the strategy of cocrystal formation. Mechanochemical screening by liquid-assisted grinding generated four cocrystals of paracetamol that readily form tablets by direct compression. Computational studies reveal the mechanical properties can be related to structural features, before all the formation of hydrogen-bonded layers.

[1]  D. Allan,et al.  The formation of paracetamol (acetaminophen) adducts with hydrogen-bond acceptors. , 2002, Acta crystallographica. Section B, Structural science.

[2]  Gautam R. Desiraju,et al.  Supramolecular Synthons in Crystal Engineering—A New Organic Synthesis , 1995 .

[3]  T. Steiner The hydrogen bond in the solid state. , 2002, Angewandte Chemie.

[4]  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.

[5]  A. Albinati,et al.  Molecular motion in crystalline naphthalene: analysis of multi-temperature X-ray and neutron diffraction data. , 2006, The journal of physical chemistry. A.

[6]  T. Friščić,et al.  Cocrystal architecture and properties: design and building of chiral and racemic structures by solid-solid reactions. , 2007, Faraday discussions.

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

[8]  William Jones,et al.  Pharmaceutical Cocrystals: An Emerging Approach to Physical Property Enhancement , 2006 .

[9]  Chick C. Wilson Variable temperature study of the crystal structure of paracetamol (p-hydroxyacetanilide), by single crystal neutron diffraction , 2000 .

[10]  J. Sherwood,et al.  Two new paracetamol/dioxane solvates--a system exhibiting a reversible solid-state phase transformation. , 2003, Journal of pharmaceutical sciences.

[11]  S. Veesler,et al.  Pure Paracetamol for direct compression Part I. Development of sintered-like crystals of Paracetamol , 1995 .

[12]  G. Day,et al.  The prediction, morphology, and mechanical properties of the polymorphs of paracetamol. , 2001, Journal of the American Chemical Society.

[13]  T. Friščić,et al.  Structural Equivalence of Br and I Halogen Bonds: A Route to Isostructural Materials with Controllable Properties , 2008 .

[14]  L. Fábián,et al.  Exploring the relationship between cocrystal stability and symmetry: is Wallach's rule applicable to multi-component solids? , 2008, Chemical communications.

[15]  Ning Shan,et al.  The role of cocrystals in pharmaceutical science. , 2008, Drug discovery today.

[16]  J. Burley,et al.  Enforcing Ostwald's rule of stages: isolation of paracetamol forms III and II. , 2007, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[17]  J. C. Guyot,et al.  A new pure paracetamol for direct compression : the orthorhombic form. , 1996 .

[18]  Graeme M. Day,et al.  Elastic Constant Calculations for Molecular Organic Crystals , 2001 .

[19]  W. Jones,et al.  Screening for crystalline salts via mechanochemistry. , 2006, Chemical communications.

[20]  Margaret C. Etter,et al.  Encoding and decoding hydrogen-bond patterns of organic compounds , 1990 .

[21]  Jeanette T. Dunlap,et al.  Crystal engineering approach to forming cocrystals of amine hydrochlorides with organic acids. Molecular complexes of fluoxetine hydrochloride with benzoic, succinic, and fumaric acids. , 2004, Journal of the American Chemical Society.

[22]  W. David,et al.  Pressure-induced formation of a solvate of paracetamol. , 2003, Chemical communications.

[23]  E. Boldyreva,et al.  Variable temperature (100–360 K) single-crystal X-ray diffraction study of the orthorhombic polymorph of paracetamol (p-hydroxyacetanilide) , 2004 .

[24]  Jason C. Cole,et al.  DASH: a program for crystal structure determination from powder diffraction data , 2006 .

[25]  Aeri Park,et al.  The salt-cocrystal continuum: the influence of crystal structure on ionization state. , 2007, Molecular pharmaceutics.

[26]  C. Pulham,et al.  Co-crystallisation at high pressure—an additional tool for the preparation and study of co-crystals , 2008 .

[27]  Changquan Calvin Sun,et al.  Improving Mechanical Properties of Caffeine and Methyl Gallate Crystals by Cocrystallization , 2008 .

[28]  J. Bernstein Pinching polymorphs , 2005, Nature materials.

[29]  K. Harris,et al.  Direct structure determination of a multicomponent molecular crystal prepared by a solid-state grinding procedure. , 2003, Journal of the American Chemical Society.

[30]  K. Kachrimanis,et al.  Effects of Moisture and Residual Solvent on the Phase Stability of Orthorhombic Paracetamol , 2008, Pharmaceutical Research.

[31]  G Nichols,et al.  Physicochemical characterization of the orthorhombic polymorph of paracetamol crystallized from solution. , 1998, Journal of pharmaceutical sciences.

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

[33]  Aeri Park,et al.  Use of a Glutaric Acid Cocrystal to Improve Oral Bioavailability of a Low Solubility API , 2006, Pharmaceutical Research.

[34]  László Fábián,et al.  Cambridge Structural Database Analysis of Molecular Complementarity in Cocrystals , 2009 .

[35]  D. Allan,et al.  Preparation and crystal structure of a trihydrate of paracetamol. , 2002, Journal of pharmaceutical sciences.

[36]  C. Pulham,et al.  A paracetamol–morpholine adduct , 2002 .

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

[38]  C. Pulham,et al.  Paracetamol monohydrate at 150 K , 2002 .

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