Indomethacin–Saccharin Cocrystal: Design, Synthesis and Preliminary Pharmaceutical Characterization

H. Brittain. Polymorphism in pharmaceutical solids. Marcel Dekker, New York, 1999, p. 95.

S. M. Berge, L. D. Bighley, and D. C. Monkhouse. Pharmaceutical salts. J. Pharm. Sci. 66:1–19 (1977).

S. R. Byrn, R. P. Pfeiffer, and J. G. Stowell. Solid State Chemistry of Drugs, SSCI Inc, West Lafayete, IN, 1999.

A. T. M. Serajuddin. Solid dispersion of poorly water-soluble drugs: early promises, subsequent problems, and recent breakthroughs. J. Pharm. Sci. 88:1058–1066 (1999).

P. H. Stahl and C. G. Wermuth. Handbook of pharmaceutical salts, Verlag Helvetica Chimica Acta; Zurich and Wiley-VCH, Weinheim, 2002.

A. M. Kaushal, P. Gupta, and A. K. Bansal. Amorphous drug delivery systems: Molecular aspects, design and performance. Crit. Rev. in Ther. Drug Carrier Syst. 21:133–193 (2004).

D. P. McNamara, S. L. Childs, J. Giordano, A. Iarriccio, J. Cassidy, M. S. Shet, R. Mannion, E. O’Donnell, and A. Park. Use of a glutaric acid cocrystal to improve oral bioavailability of a low solubility API. Pharm. Res. 23:1888–1897 (2006).

C. B. Aakeröy and D. J. Salmon. Building co-crystals with molecular sense and supramolecular sensibility. Cryst. Eng. Comm. 7:439–448 (2005).

Ö. Almarsson and M. J. Zaworotko. Crystal engineering of the composition of pharmaceutical phases. Do pharmaceutical co-crystals represent a new path to improved medicines? Chem. Commun. (Camb.) 1889–1896 (2004).

M. C. Etter. Hydrogen bonds as design elements in organic chemistry. J. Phys. Chem. 95:4601–4610 (1990).

M. C. Etter. Hydrogen bond directed cocrystallization and molecular recognition properties of acyclic imides. J. Am. Chem. Soc. 113 (1991).

G. R. Desiraju. Supramolecular synthons in crystal engineering—a new organic synthesis. Angew. Chem., Int. Ed. Engl. 34:2311–2327 (1995).

P. Vishweshwar, J. A. McMahon, J. A. Bis, and M. J. Zaworotko. Pharmaceutical co-crystals. J. Pharm. Sci. 95:499–516 (2006).

A. V. Trask, W. D. Motherwell, and W. Jones. Physical stability enhancement of theophylline via cocrystallization. Int. J. Pharm. 320:114–123 (2006).

S. L. Childs, L. J. Chyall, J. T. Dunlap, V. N. Smolenskaya, B. C. Stahly, and G. P. Stahly. 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. 126:13335–13342 (2004).

J. R. Dipalma. Basic Pharmacology in Medicine, McGraw-Hill, New York, 1976.

P. A. Slavina, D. B. Sheena, E. E. A. Shepherda, J. N. Sherwooda, N. Feederb, R. Dochertyb, and S. Milojevic. Morphological evaluation of the γ-polymorph of indomethacin. J. Cryst. Growth 237–239:300–305 (2002).

T. Matsumoto and G. Zografi. Physical properties of solid molecular dispersions of indomethacin with poly(vinylpyrrolidone) and poly(vinylpyrrolidone-co-vinyl-acetate) in relation to indomethacin crystallization. Pharm. Res. 16:1722–1728 (1999).

N. Bandi, W. Wei, C. B. Roberts, L. P. Kotra, and U. B. Kompella. Preparation of budesonide and indomethacin hydroxypropyl-beta-cyclodextrin (HPBCD) complexes using a single-step, organic-solvent-free supercritical fluid process. Eur. J. Pharm. Sci. 23:159–168 (2004).

M. Yoshioka, B. C. Hancock, and G. Zografi. Crystallization of indomethacin from the amorphous state below and above its glass transition temperature. J. Pharm. Sci. 83:1700–1705 (1994).

R. D. B. Walsh, M. W. Bradner, S. Fleischman, L. A. Morales, B. Moulton, N. Rodriguez-Hornedo, and M. J. Zaworotko. Crystal engineering of the composition of pharmaceutical phases. Chem. Commun. 186–187 (2003).

R. Banerjee, P. M. Bhatt, N. V. Ravindra, and G. R. Desiraju. Saccharin salts of active pharmaceutical ingredients, their crystal structures, and increased water solubilities. Cryst. Growth Des. 5:2299–2309 (2005).

T. Friščić, A. V. Trask, W. Jones, and W. D. S. Motherwell. Screening for inclusion compounds and systematic construction of three-component solids by liquid-assisted grinding. Angew. Chem. Int. Ed. 45:7546–7550 (2006).

G. M. Sheldrick. SHELX-97: Program for the Solution and refinement of Crystal Structures, University of Göttingen, Germany, 1997.

S. Hess, U. Teubert, J. Ortwein, and K. Eger. Profiling indomethacin impurities using high-performance liquid chromatography and nuclear magnetic resonance. Eur. J. Pharm. Sci. 14:301–311 (2001).

P. J. Cox and P. L. Manson. Indomethacin tert-butanol solvate at 120 K. Acta Crystallogr. E59:o1189–o1191 (2003).

X. Chen, K. R. Morris, J. J. Griesser, S. R. Byrn, and J. G. Stowell. Reactivity differences of indomethacin solid forms with ammonia gas. J. Am. Chem. Soc. 124:15012–15019 (2002).

J. G. Stowell, S. R. Byrn, G. Zografi, and M. Yoshioka. Private Communication (2002).

J. L. Wardell, J. N. Low, and C. Glidewell. Saccharin, redetermined at 120 K: a three-dimensional hydrogen-bonded framework. Acta Crystallogr. E61:o1944–o1946 (2005).

S. G. Fleischman, S. S. Kuduva, J. A. McMahon, B. Moulton, R. D. B. Walsh, N. Rodriguez-Hornedo, and M. J. Zaworotko. Crystal engineering of the composition of pharmaceutical phases: multiple-component crystalline solids involving carbamazepine. Cryst. Growth Des. 3:909–919 (2003).

The refcodes of the crystal structures with acid-dimer and imide-dimer or amide dimer synthons in the CSD: Acid-Imide: XUNHIX, XUNHUJ, GUGCUG, PAXNIL, YEJMOP. Acid-Amide: LORRIT, NUHYEU, TORQIA, TORQOG, WARXIW.

M. O’Brien, J. McCauley, and E. Cohen. Indomethacin. Anal. Profiles Drug Subst. 13:211–238 (1984).

G. Jovanovski. Metal saccharinates and their complexes with N-donor ligands. CCACAA 73:843–868 (2000)

Y. Hase. The infrared and raman spectra of phthalimide, N-d-phthalimide and potassium phthalimide. J. Mol. Struct. 48:33–42 (2005).

G. Jovanovski. The SO2 stretching vibrations in some metal saccharinates: spectra-structure correlations. Spectrosc. Lett. 28:1095–1109 (1995).

M. A. R. Matos, M. S. Miranda, V. M. F. Morais, and J. F. Liebman. Saccharin: a combined experimental and computational thermochemical investigation of a sweetener and sulfonamide. Mol. Phys. 103:221–228 (2005).

Simulated PXRD pattern from single crystal X-ray diffraction obtained from CSD (Ref code: SCCHRN02).

S. J. Nehm, B. R. Spong, and N. R. Hornedo. Phase solubility diagrams of cocrystals are explained by solubility product and solution complexation. Cryst. Growth Des. 6:592–600 (2006).

N. R. Hornedo, S. J. Nehm, K. F. Seefeldt, Y. P. Torres, and C. J. Falkiewicz. Reaction crystallization of pharmaceutical molecular complexes. Mol. Pharm. 3:362–367 (2006).

K. J. Crowley and G. Zografi. Cryogenic griding of indomethaci polymorphs and solvates: assessment of amorphous phase formation and amorphous phase physical stability. J. Pharm. Sci. 91:492–507 (2002).

B. C. Hancock and G. Zografi. The relationship between the glass transition temperature and water content of amorphous pharmaceutical solids. Pharm. Res. 11:471–477 (1994).

A. Jayasankar, A. somwangthanaroj, Z. J. Shao, and N. R. Hornedo. Cocrystal formation during cogrinding and storage is mediated by amorphous phase. Pharm. Res. 23:2381–2392 (2006).