The salt-cocrystal continuum: The influence of crystal structure on ionization state

Molecular Pharmaceutics

Volumn 4, Issue 3, 2007, Pages 323-338

  Childs, Scott L ^a   Stahly, G Patrick ^a   Park, Aeri ^a,b  

^a Aptuit Inc   (United States)

^b SSCI Incorporated   (United States)

Author keywords

Cocrystal; Molecular complex; Pharmaceutical; pKa, proton transfer; Salt

Indexed keywords

CRYSTALLIN; MALEIC ACID; NIFLUMIC ACID; SODIUM CHLORIDE; THEOPHYLLINE;

ACID BASE BALANCE; ARTICLE; CRYSTAL STRUCTURE; DRUG ISOLATION; INFRARED SPECTROSCOPY; IONIZATION; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; PRIORITY JOURNAL; PROTON TRANSPORT; SUSTAINED RELEASE PREPARATION; X RAY DIFFRACTION;

CRYSTALLIZATION; CRYSTALLOGRAPHY, X-RAY; HYDROGEN-ION CONCENTRATION; IONS; MAGNETIC RESONANCE SPECTROSCOPY; MALEATES; MODELS, MOLECULAR; MOLECULAR STRUCTURE; NIFLUMIC ACID; POWDER DIFFRACTION; PROTONS; SALTS; SPECTROSCOPY, FOURIER TRANSFORM INFRARED; THEOPHYLLINE;

EID: 34250791543     PISSN: 15438384     EISSN: 15438392     Source Type: Journal    
DOI: 10.1021/mp0601345     Document Type: Article

References (82)

1. Datta, S.; Grant, D. J. W. Crystal structures of drugs: Advances in determination, prediction and engineering. Nat. Rev. Drug Discovery 2004, 3, 42-57.
2. Ling, A. R.; Baker, J. L. Halogen derivatives of quinone. Part III. Derivatives of quinhydrone. J. Chem. Soc. 1893, 63, 1314-1327.
3. (a) Rodriguez-Spong, B.; Price, C. P.; Jayasankar, A.; Matzger, A. J.; Rodriguez-Hornedo, N. General principles of pharmaceutical solid polymorphism: a supramolecular perspective. Adv. Drug Delivery Rev. 2004, 56, 241-274.
4. (b) Childs, S. L.; Chyall, L. J.; Dunlap, J. T.; Smolenskaya, V. N.; Stahly, B. C.; Stahly, G. P. Crystal engineering approach to forming cocrystals of amine hydrochlorides with organic acids. Molecular complexes of fluoxetine hydrochloride with benzoic, succinic, and fumaric acids. J. Am. Chem. Soc. 2004, 126, 13335-13342.
5. (c) Almarsson, O.; Zaworotko, M. J. Crystal engineering of the composition of pharmaceutical phases. Do pharmaceutical co-crystals represent a new path to improved medicines? Chem. Commun. 2004, 17, 1889-1896.
6. (d) Hilfiker, R. Polymorphism in the pharmaceutical industry; Wiley-VCH, John Wiley: Weinheim, Chichester, 2006.
7. (e) Aakeroy, C. B. Crystal engineering: Strategies and architectures. Acta Crystallogr., Sect. B: Struct. Sci. 1997, 53, 569-586.
8. We use "cocrystal" because we believe that it is the most grammatically correct term according to the rules of English usage. For instance, see: Wilson, K. G. The Columbia Guide to Standard American English; MJF Books: New York, 1993; p 99.
9. Further discussion on the definitions of salts and cocrystals are detailed in the following publication: Stahly, G. P. Diversity in Single-Component and Multiple-Component Crystals. The Search for and Prevalence of Polymorphs and Cocrystals. Cryst. Growth Des., in press.
10. Lide, D. R. CRC Handbook of Chemistry and Physics, 81st ed.; CRC Press: Boca Raton, 2000; pp 2-55.
11. (a) Huang, K.-S.; Britton, D.; Etter, M. C.; Byrn, S. R. A novel class of phenol-pyridine co-crystals for second harmonic generation. J. Mater. Chem. 1997, 7, 713-720.
12. (b) Stahl, P. H.; Wermuth, C. G. ed. Handbook of pharmaceutical salts: properties, selection, and use; International Union of Pure and Applied Chemistry, VHCA; Wiley-VCH: Weinheim, New York, 2002.
13. (c) Smith, M.; March, J.; March, J. March's advanced organic-chemistry: reactions, mechanisms, and structure, 5th ed.; J. Wiley: New York, 2001.
14. (d) Bhogala, B. R.; Basavoju, S.; Nangia, A. Tape and layer structures in cocrystals of some di- and tricarboxylic acids with 4,4′-bipyridines and isonicotinamide. From binary to ternary cocrystals. CrystEngComm 2005, 7, 551-562.
15. APEX II, 2005, Bruker AXS, Inc., Analytical X-ray Systems, 5465 East Cheryl Parkway, Madison, WI 53711-5373.
16. SAINT Version 6.45A, 2003, Bruker AXS, Inc., Analytical X-ray Systems, 5465 East Cheryl Parkway, Madison, WI 53711-5373.
17. SHELXTL V6.12, 2002, Bruker AXS, Inc., Analytical X-ray Systems, 5465 East Cheryl Parkway, Madison, WI 53711-5373.
18. Wilson, A. J. C., Ed. International Tables for X-ray Crystallography; Kynoch, Academic: Dordrecht, 1992; Vol. C, Tables 6.1.1.4 (pp 500-502) and 4.2.6.8 (pp 219-222).
19. Rowland, R. S.; Taylor, R. Intermolecular Nonbonded Contact Distances in Organic Crystal Structures: Comparison with Distances Expected from van der Waals Radii. J. Phys. Chem. 1996, 100, 7384-7391.
20. (a) Ratajczak, H.; Orville-Thomas, W. J. Molecular interactions; J. Wiley: Chichester [Engl.], New York, 1980.
21. (b) Lehtonen, O.; Hartikainen, J.; Rissanen, K.; Ikkala, O.; Pietila, L. O. Hydrogen bonding and protonation in acid-base complexes: Methanesulfonic acid-pyridine. J. Chem. Phys. 2002, 116, 2417-2424.
22. (c) Steiner, T. The hydrogen bond in the solid state. Angew. Chem., Int. Ed. 2002, 41, 49-76.
23. (a) Majerz, I.; Malarski, Z.; Sobczyk, L. Proton transfer and correlations between the C-O, O-H, N-H and O⋯N bond lengths in amine phenolates. Chem. Phys. Lett. 1997, 274, 361-364.
24. (b) Aakeroy, C. B.; Hussain, I.; Desper, J. 2-Acetaminopyridine: A highly effective cocrystallizing agent. Cryst. Growth Des. 2006, 6, 474-480.
25. Boenigk, D.; Mootz, D. The System Pyridine-Hydrogen Fluoride at Low Temperatures: Formation and Crystal Structures of Solid Complexes with Very Strong NHF and FHF Hydrogen Bonding. J. Am. Chem. Soc. 1988, 110, 2135-2139.
26. (a) Hamilton, W. C.; Ibers, J. A. Hydrogen bonding in solids; methods of molecular structure determination; W. A. Benjamin: New York, 1968.
27. (b) Bellamy, L. J. The infra-red spectra of complex molecules, 2nd ed.; Methuen, Wiley: London, New York, 1958.
28. (c) Bellamy, L. J. The infra-red spectra of complex molecules, 2d ed.; Chapman and Hall: London, New York, 1980.
29. (d) Williams, D. H.; Fleming, I. Spectroscopic methods in organic chemistry, 2d ed.; McGraw-Hill: London, New York, 1973.
30. (e) Gunnar, A.; Zundel, G. Phenol-amine hydrogen bonds with large proton polarizabilities. J. Chem. Soc, Faraday Trans. 1 1984, 80, 553-561.
31. (f) Etter, M. C.; Reutzel, S. M. Hydrogen-Bond Directed Cocrystallization and Molecular Recognition Properties of Acyclic Imides. J. Am. Chem. Soc. 1991, 113, 2586-2598.
32. (g) Wojciechowski, G.; Ratajczak-Sitarz, M.; Katrusiak, A.; Schilf, W.; Przybylski, P.; Brzezinski, B. Crystal structure of Schiff base derivative of 2,2′-dihydroxybiphenyl-3-carbaldehyde with n-butylamine. J. Mol. Struct. 2003, 650, 191-199.
33. (h) Johnson, S. L.; Rumon, K. A. Infrared spectra of solid 1:1 pyridine-benzoic acid complexes; the nature of the hydrogen bond as a function of the acid-base levels in the complex. J. Phys. Chem. 1965, 69, 74-86.
34. (i) Aakeroy, C. B.; Desper, J.; Fasulo, M. E. Improving success rate of hydrogen-bond driven synthesis of co-crystals. CrystEngComm 2006, 8, 586-588.
35. (j) Pimentel, G. C.; McClellan, A. L. The hydrogen bond; W. H. Freeman, Reinhold Corp.: New York, San Francisco, 1960.
36. 15N NMR spectroscopy. J. Am. Chem. Soc. 2006, 128, 8199-210.
37. Steiner, T.; Majerz, I.; Wilson, C. C. First O-H-N Hydrogen Bond with a Centered Proton Obtained by Thermally Induced Proton Migration. Angew. Chem., Int. Ed. 2001, 40, 2651-2654.
38. Cowan, J. A.; Howard, J. A.; McIntyre, G. J.; Lo, S. M.; Williams, I. D. Variable-temperature neutron diffraction studies of the short, strong N...O hydrogen bonds in the 1:2 co-crystal of benzene-1,2,4,5-tetracarboxylic acid and 4,4′-bipyridyl. Acta Crystallogr., Sect. B: Struct. Sci. 2003, 59, 794-801.
39. Wilson, C. C. Migration of the proton in the strong O-H.O hydrogen bond in urea-phosphoric acid (1/1). Acta Crystallogr., Sect. B: Struct. Sci. 2001, 57, 435-439.
40. +N Equilibrium as a Function of the Donor and Acceptor. J. Chem. Soc, Faraday Trans. 1 1984, 80, 553-561.
41. (b) Malarski, Z.; Rospenk, M.; Sobczyk, L.; Grech, E. Dielectric and Spectroscopic Studies of Pentachlorophenol-Amine Complexes. J. Phys. Chem. 1982, 86, 401-406.
42. Lynch, D. E.; Smith, G.; Freney, D.; Byriel, K. A.; Kennard, C. H. L. Molecular Cocrystals of Carboxylic-Acids. XV. Preparation and Characterization of Heterocyclic Base Adducts with a Series of Carboxylic-Acids, and the Crystal-Structures of the Adducts of 2-Aminopyrimidine with 2,6-Dihydroxybenzoic Acid, 4-Aminobenzoic Acid, Phenoxyacetic Acid, (2,4-Dichlorophenoxy)-Acetic Acid, (3,4-Dichlorophenoxy)-Acetic Acid and Salicylic-Acid, and 2-Aminopyridine with 2,6-Dihydroxybenzoic Acid. Aust. J. Chem. 1994, 47, 1097-1115.
43. Clark, J. H.; Jones, C. W. Solvent-dependent Proton Transfer in a Strongly Hydrogen Bonded Fluoride Complex. J. Chem. Soc., Chem. Commun. 1990, 1786-1787.
44. Wiechert, D.; Mootz, D. Molecular beside ionic: Crystal structures of a 1/1 and a 1/4 adduct of pyridine and formic acid. Angew. Chem., Int. Ed. 1999, 38, 1974-1976.
45. Arora, K. K.; PrakashaReddy, J.; Pedireddi, V. R. Pyridine mediated supramolecular assemblies of 3,5-dinitro substituted benzoic acid, benzamide and benzonitrile. Tetrahedron 2005, 61, 10793-10800.
46. Haynes, D. A.; Jones, W.; Motherwell, W. D. Cocrystallisation of succinic and fumaric acids with lutidines: a systematic study. CrystEngComm 2006, 8, 830-840.
47. Braga, D.; Maini, L.; de Sanctis, G.; Rubini, K.; Grepioni, F.; Chierotti, M. R.; Gobetto, R. Mechanochemical preparation of hydrogen-bonded adducts between the diamine 1,4-diazabicyclo-[2,2,2]octane and dicarboxylic acids of variable chain length: An X-ray diffraction and solid-state NMR study. Chem. Eur. J. 2003, 9, 5538-5548.
48. Takasuka, M.; Nakai, H.; Shiro, M. Infrared Spectral and X-Ray Studies of Polymorphic Forms of 2-(2-methyl-3-chloroanilino) nicotinic Acid. J. Chem. Soc., Perkin Trans. 2 1982, 1061-1067.
49. CSD refcodes BIXGIY, BIXGIY02, BIXGIY03, and BIXGIY04.
50. Krishna, Murthy, H. M.; Vijayan, M. 2-{[3-Trifluoromethyl-(phenyl)]amino} -3-pyridinecarboxylic Acid (Niflumic Acid). Acta Crystallogr., Sect. B: Struct. Sci. 1979, 35, 262-263.
51. Romero, S.; Bustamante, P.; Escalera, B.; Cirr, M.; Mura, P. Characterization of the Solid Phases of Paracetamol and Fenamates in Equilibrium in Saturated Solutions. J. Therm. Anal. Calorim. 2004, 77, 541-554.
52. Vrecer, F.; Vrbinc, M.; Meden, A. Characterization of piroxicam crystal modifications. Int. J. Pharm. 2003, 256, 3-15.
53. Childs, S. L. and Hardcastle, K. I. Cocrystals of piroxicam with carboxylic acids. Cryst. Growth Des., in press.
54. (a) Groter, R. Theophylline compound. U.S. Patent 919,161, 1908.
55. (b) Veith, H. Diurectic compound and process of making it. U.S. Patent 1,547,698, 1925.
56. (c) Greenbaum, F. R. New water soluble theophylline compound. Am. J. Pharm. 1937, 109, 550-554.
57. (d) Ladenburg, K.; Duesel, B. F.; Fand, T. I. Process for the preparation of therapeutic compounds. U.S. Patent 2,776,287, 1957.
58. Only simple organic theophylline salts were included in Tables 2 and 3. Tables do not include the known metal salts of theophylline.
59. Jeanjean, B.; Alberola, S.; Terol, A.; Sabon, F. Study of paracetamol-theophylline and paracetamol-caffeine associations. Ann. Pharm. Fr. 1979, 37, 95-100.
60. Shefter, E. Structural studies on complexes. IV. Crystal structure of a 1:1 5-chlorosalicylic acid and theophylline complex. J. Pharm. Sci. 1969, 58, 710.
61. (a) Borazan, H. N.; Al-Ani, N. I. Charge transfer effect through hydrogen bonding in caffeine-p-cresol and theophylline-p-cresol complexes. J. Pharm. Sci. 1980, 69, 613-5.
62. (b) Nishijo, J.; Takenaka, F. Studies on the properties of the complex-medicines. I. Differential thermogravimetric analysis of aminophylline (author's transl.). Yakugaku Zasshi 1979, 99, 824-829.
63. (c) Madarasz, J.; Bombicz, P.; Czugler, M.; Pokol, G. Comparison of theophyllinato Cu (II) complexes of ethanolamine and diethanolamine part 2. Structure and thermal study of the dimeric complex with diethanolamine. Polyhedron 2000, 19, 457-463.
64. (d) Bombicz, P.; Madarasz, J.; Forizs, E.; Foch, I. Structure and thermal behavior of (SPY-5-12)-(2-aminoethanol-N)(2-aminoethanol-N,O)- bis(theophyllinato)copper(II)dihydrate: a model for DNA interactions. Polyhedron 1997, 16, 3601-3607.
65. (e) Nishijo, J.; Takenaka, F. Interaction of theophylline with several aliphatic organic dibasic acids in a solid state. Yakugaku Zasshi 1983, 103, 819-824.
66. (f) Sekiya, M.; Yoshino, T.; Tanaka, H.; Ishido, Y. Mechanism of Acid Catalysis and New Activating Agents in Fusion Reaction of an Acylated Sugar with a Purine Derivative. Bull. Chem. Soc. Jpn. 1973, 46, 556-561.
67. (g) Madarasz, J.; Bombicz, P.; Jarmi, K.; Ban, M.; Pokol, G.; Gal, S. Thermal, FTIR and XRD study on some 1:1 molecular compounds of theophylline. J. Therm. Anal. Calorim. 2002, 69, 281-290.
68. (h) Nishijo, J.; Ohno, K.; Nishimura, K. Interaction of Theophylline with Benzylamine in the Solid-State. Chem. Pharm. Bull. 1982, 30, 2219-2222.
69. (i) Nishijo, J.; Ohno, K.; Nishimura, K.; Hukuda, M.; Ishimaru, H. Solid Complexes of Theophylline with Several Aliphatic Monoamines. Chem. Pharm. Bull. 1982, 30, 391-397.
70. (j) Okano, T.; Aita, K.; Ikeda, K. Electronic properties of N-heteroaromatics. XII. On the mode of interaction between theophylline and ethylenediamine in aqueous solution. Chem. Pharm. Bull. 1967, 15, 1621-1625.
71. (k) Nishijo, J.; Furukawa, H.; Nakano, M. Solid Complexes of Theophylline with Ethylenediamine Analogs. Yakugaku Zasshi 1980, 100, 493-499.
72. (l) Ban, M.; Madarasz, J.; Bombicz, P.; Pokol, G.; Gal, S. Thermal and structural study on the lattice compound 1,4-diammoniumbutane bis(theophyllinate). Thermochim. Acta 2004, 420, 105-109.
73. Trask, A. V.; Motherwell, W. D.; Jones, W. Physical stability enhancement of theophylline via cocrystallization. Int. J. Pharm. 2006, 320, 114-123.
74. O'Neil, M. J.; Merck & Co., The Merck index: an encyclopedia of chemicals, drugs, and biologicals, 13th ed.; Merck: Whitehouse Station, NJ, 2001.
75. The solid that we obtained contained a small amount of theophylline along with the theophylline:1,7-heptanediamine hydrate complex. This was confirmed by comparing the XRPD data reported by Nishijo to the XRPD data for the sample we isolated. The IR data for our sample also shows a theophylline component. Taking this into account, the conclusion that mixed ionization states are present in the theophylline:1,7-heptanediamine hydrate complex is still valid.
76. McNamara, D. P.; Childs, S. L.; Giordano, J.; Iarriccio, A.; Cassidy, J.; Shet, M. S.; Mannion, R.; O'Donnell, E.; Park, A. Use of a glutaric acid cocrystal to improve oral bioavailability of a low solubility API. Pharm. Res. 2006, 23, 1888-1897.
77. Phadnis, N. V.; Suryanarayanan, R. Polymorphism in anhydrous theophylline - implications on the dissolution rate of theophylline tablets. J. Pharm. Sci. 1997, 86, 1256-1263.
78. Shonle, A. H. Ethanolamine salts of theophylline and process of making them. U.S. Patent 1,867,332, 1932.
79. Koehlstaedt, D. R. 583,054 Kl. 12, Group 7, 1935.
80. Shelton, R. S. Butanolamine salts of theophylline. U.S. Patent 2,404,319, 1946.
81. (a) Giannini, M.; Brogioni, M. Antibronchospastic water-soluble pharmaceutical compositions. GB Patent 2,100,982, 1982.
82. (b) Johnston, A.; Hedges, A.; Freedman, A.; Aldhous, M. E.; Weerasuriya, K.; Turner, P. The Pharmacokinetics of Lysine Theophylline, a New Soluble Theophylline, in Human Volunteers. Postgrad. Med. J. 1983, 59, 86-87.