Structure and physicochemical properties of meloxicam, a new NSAID

European Journal of Pharmaceutical Sciences

Volumn 4, Issue 3, 1996, Pages 175-187

  Luger, Peter ^a   Daneck, Klaus ^b   Engel, Wolfhard ^b   Trummlitz, Günter ^b   Wagner, Klaus ^b  

^a FREIE UNIVERSITÄT BERLIN   (Germany)

^b BOEHRINGER INGELHEIM PHARMA GMBH AND CO KG   (Germany)

Author keywords

Meloxicam; NSAID; Partition coefficients; pK(a) values; Solubility

Indexed keywords

ACETYLSALICYLIC ACID; DICLOFENAC; KETOPROFEN; MELOXICAM; NONSTEROID ANTIINFLAMMATORY AGENT; PIROXICAM; TENOXICAM;

ARTICLE; CONFORMATION; CRYSTAL STRUCTURE; DRUG SOLUBILITY; DRUG STRUCTURE; NUCLEAR MAGNETIC RESONANCE; PARTITION COEFFICIENT; PHYSICAL CHEMISTRY; PRIORITY JOURNAL; X RAY CRYSTALLOGRAPHY;

EID: 0029886150     PISSN: 09280987     EISSN: None     Source Type: Journal    
DOI: 10.1016/0928-0987(95)00046-1     Document Type: Article

References (37)

1. Aue, W.P., Bartholdi, E. and Ernst, R.R. (1976) Two-dimensional spectroscopy. Application to nuclear magnetic resonance. J. Chem. Phys. 64, 2220-2248.
2. Bax, A. and Morris, G.A. (1981) An approved method for heteronuclear chemical shift correlation by two-dimensional NMR. J. Magn. Reson. 42, 501.
3. Bax, A. and Davis, D.G. (1985) Practical aspects of two-dimensional transverse NOE spectroscopy. J. Magn. Reson. 63, 207-213.
4. Bernhard, E. and Zimmermann, F. (1984) Contribution to the understanding of oxicam ionization constants. Arzneim.-Forsch. 34, 647-648.
5. 2O. Acta Crystallogr. C40, 989-990.
6. Bordner, J., Hammen, P.D. and Whipple, E.B. (1989) Deuterium isotope effects on carbon-13 NMR shifts and the tautomeric equilibrium in N-substituted pyridyl derivatives of piroxicam. J. Am. Chem. Soc. 111, 6572-6578.
7. Brooks, P.M. and Day, R.O. (1991) Non steroidal anti-inflammatory drugs - differences and similarities. N. Engl. J. Med. 324, 1716-1725.
8. 2S. Cryst. Struct. Commun. 10, 121-124.
9. Cremer, D. and Pople, J.A. (1975) A general definition of ring puckering coordinators. J. Am. Chem. Soc. 97, 1354-1358.
10. Day, R.O., Graham, G.G., Williams, K.M. and Brooks, P.M. (1988) Variability in response to NSAIDs. Fact or Fiction? Drugs 36, 643-651.
11. Ellis, G.A. and Blake D.R. (1993) Why are non-steroidal anti-inflammatory drugs so variable in their efficacy? A description of ion trapping. Ann. Rheum. Dis. 52, 241-243.
12. Engelhardt, G. (1994) Meloxicam, a potent inhibitor of COX-2. Abstract presented at the 9th International Conference on Prostaglandins and Related Compounds. Florence, Italy, 6-10 June 1994.
13. Engelhardt, G., Homma, D., Schlegel, K. and Schnitzler, Chr. (1996) Anti-inflammatory, analgesic, antipyretic and related properties of meloxicam, a new non-steroidal anti-inflammatory agent with favourable gastrointestinal tolerance. Inflamm. Res., in press.
14. Engelhardt, G., Bögel, R., Schnitzer, Chr. and Utzmann, R. (1994) Meloxicam: Influence on arachidonic acid metabolism. Part 1. In vitro findings. Data on file, Boehringer Ingelheim.
15. Hall, S.R., Flack, H.D. and Stewart, J.M, editors (1992) XTAL Program system 3.2 in User's Manual. Universities of Western Australia, Geneva and Maryland.
16. Herzfeldt, C.D. and Kümmel, R. (1983) Dissociation constants, solubilites and dissolution rates of some selected Non steroidal anti-inflammatories. Drug. Dev. Ind. Pharm. 9, 767-793.
17. Keller, E. (1988) Schakal-88, a program for graphic representation of molecular and crystallographic models, University of Freiburg, Freiburg, Germany.
18. 1 (COLOC). J. Magn. Reson. 57, 331-336.
19. Kessler, H., Griesinger, C. and Wagner, K. (1987) Conformation of side chains in peptides using heteronuclear coupling constants obtained by two-dimensional NMR spectroscopy. J. Am. Chem. Soc. 109, 6982-6983.
20. Kojić-Prodić, B. and Ružić-Toroš, Ž. (1982) Structure of the antiinflammatory drug 4-hydroxy-2-methyl-N-2-pyridyl-2H-1 λ,2-benzothiazine-3-carboxamide 1, 1-dioxide (piroxicam). Acta Crystallogr. B38, 2948-2951.
21. Luger, P. (1980) Modem X-ray analysis on single crystals. De Gruyter, Berlin, p. 229.
22. Luger, P. and Bülow, R. (1983) Puck2, an improved version of the Cremer-Pople puckering program. J. Appl. Crystalogr. 16, 431.
23. Main, P., Lessinger, L., Woolfsen, M.M., Germain, G. and Declerq, J.P. (1977) MULTAN77, a system of computer programs for the automatic solution of crystal structures from X-ray diffraction data, Universities of York, UK and Louvain, Belgium.
24. Meade, E.A., Smith, W.L. and DeWitt, D.L. (1993) Differential inhibition of prostaglandin endoperoxide synthase (cyclooxygenase) isozymes by aspirin and other non-steroidal anti-inflammatory drugs. J Biol Chem. 268, 6610-6614.
25. Ovchinnikov, Y. and Ivanov, V.T. (1975) Conformational states and biological activity of cyclic peptides. Tetrahedron 31, 2177-2209.
26. 5S. Cryst. Struct. Commun. 9, 321-324.
27. Pairet, M., Engelhardt, G., Lidbury, P. and Vane, J.R. (1996) Differential inhibition of cyclooxygenases-1 (COX-1) and -2 (COX-2) by meloxicam and its 4′-isomer: consequences on anti-inflammatory activity, gastric and renal safety, submitted.
28. 2 synthetase-1. Nature 367, 243-249.
29. Price, A.H. and Fletcher, M. (1990) Mechanisms of NSAID-induced gastroenteropathy. Drugs 40 (Suppl. 5), 1-11.
30. Reck, G., Dietz, G., Laban, G., Günther, W., Bannier, G. and Höhne, E. (1988) X-ray studies on piroxicam modifications. Pharmazie 43, 477-481.
31. Rodriguez, L., Zecchi, V. and Tartarini, A. (1984) Partition rates of some Non steroidal anti-inflammatory agents in a three-phase water/n-octanol/water system. Pharm. Acta Helv. 59, 95-97.
32. Sheldrick, G.M. (1985) In Sheldrick, G.M., Krüger, C. and Goddard, R. (Eds.), Crystallographic Computing 3. Oxford University Press, Oxford, pp. 175-189.
33. Stei, P. and Püschner, H. (1994) Intramuscular tolerance of meloxicam compared to piroxicam and diclofenac in rabbits. Scand. J. Rheumatol. (Suppl.) 98, Abstract No. 109.
34. Stewart, J.M., Machin, P.A., Ammon, H.L., Dickerson, C.W., Heck, H. and Flack, H. (1976) The X-ray system-version of March 1976. In, Technical Report TR-466, Computer Science Center, University of Maryland, College Park, MD.
35. Tsai, R.-S., Carrupt, P.-A., Tayar, N.-E., Giroud, Y., Andrade, P., Testa, B., Breé, F. and Tillement, J.-P. (1993) Physicochemical and structural properties of non-steroidal anti-inflammatory oxicams. Helv. Chim. Acta 76, 842-854.
36. Vane, J. (1994) Towards a better aspirin. Nature 367, 215-216.
37. Wiseman, E.H., Chang, Y.H. and Lombardino, J.G. (1976) Piroxicam, a novel anti-inflammatory agent. Arzneim.-Forsch. 26, 1300-1303.