Complexation study of diclofenac with β-cyclodextrin and spectrofluorimetric determination

Abstract

The inclusional complexation between the anti-inflammatory pharmaceutical diclofenac and β-cyclodextrin (β-CD) was studied by potentiometry, spectrophotometry and spectrofluorimetry, in both acid and neutral pH. Guest–host 1∶1 stoichiometries for the complexes in both media were determined, and their equilibrium constants were calculated. The values obtained from the different methods used are in very good agreement and are in the order of 10³. From the analysis of the pK_a value for diclofenac in both the absence and presence of β-CD (4.84 and 4.90 respectively), it was inferred that in the inclusion complex the carboxylic group is located outside the cavity. Further structural characterization of the inclusate was carried out by means of ¹H NMR spectra and AM1 semiempirical calculations. Based on the obtained results, a spectrofluorimetric method for the determination of diclofenac in the presence of β-CD was developed in the range of 0–5 µg ml^–1. Better limits of detection (0.03

µg ml^–1) and quantification (0.1 µg ml^–1) were obtained in this latter case with respect to those obtained in the absence of β-CD. The method was satisfactorily applied to the quantification of diclofenac in pharmaceutical preparations.

References

1. J. Szejtli, Cyclodextrins and Their Inclusion Complexes, Akademiai Kiado, Budapest, 1982.
2. S. Scypinski and L. J. Cline Love, Anal. Chem., 1984, 56, 331.
3. A. Muñoz de la Peña, T. T. Ndou, J. B. Zung, K. L. Greene, D. H. Live and I. M. Warner, J. Am. Chem. Soc., 1991, 113, 1572.
4. A. Muñoz de la Peña, I. Durán-Merás, F. Salinas, I. M. Warner and T. T. Ndou, Anal. Chim. Acta, 1991, 255, 351.
5. G. M. Escandar and A. Muñoz de la Peña, Anal. Chim. Acta, 1998, 370, 199.
6. R. Breslow and S. D. Dong, Chem. Rev., 1998, 98, 1997.
7. J. Szejtli, Cyclodextrins Technology, Kluwer Academic, Dordrecht, The Netherlands, 1988.
8. K. Takahashi, Chem. Rev., 1998, 98, 2013.
9. A. R. Hedges, Chem. Rev., 1998, 98, 2035.
10. S. Tenjarla, P. Puranajoti, R. Kasina and T. Mandal, J. Pharm. Sci., 1998, 87, 425.
11. I. Durán-Merás, A. Muñoz de la Peña, F. Salinas and I. Rodríguez Cáceres, Analyst, 1994, 119, 1215 and references cited therein.
12. J. B. Vincent, A. D. Sokolowski, T. V. Nguyen and G. Vigh, Anal. Chem., 1997, 69, 4226.
13. R. J. Hurtubise, Phosphorimetry. Theory, Instrumentation and Applications, VCH, New York, 1990, pp. 320–328.
14. G. Nelson, S. L. Neal and I. M. Warner, J. Spectrosc., 1986, 3, 24.
15. A. Blyshak, I. M. Warner and G. Patonay, Anal. Chim. Acta, 1990, 232, 239.
16. A. Orstan and J. B. A. Ross, J. Phys. Chem., 1987, 91, 2739.
17. G. M. Escandar, Spectrochim. Acta, Part A, 1999, 55, 1743.
18. G. M. Escandar, Analyst, 1999, 124, 587.
19. D. E. Furst and S. H. Dromgoole, in Drugs for Rheumatic Disease, ed. H. E. Paulus, D. E. Furst and S. H. Dromgoole, Churchill Livingstone, New York, 1987, ch. 20.
20. J. C. Botello and G. Perezcaballero, Talanta, 1995, 42, 105.
21. S. S. M. Hassan, R. M. Abdelaziz and M. S. Abdelsamad, Analyst, 1994, 119, 1993.
22. I. Kramancheva, I. Dobrev, L. Brakalov and A. Andeeva, Anal. Lett., 1997, 30, 2235.
23. Z. A. El-Sherif, M. I. Walash, M. F. El-Tarras and A. O. Osman, Anal. Lett., 1997, 30, 1881.
24. R. B. Miller, J. Chromatogr., Biomed. Appl., 1993, 616, 283.
25. G. Schmitz, H. Lepper and C. J. Estler, J. Chromatogr., Biomed. Appl., 1993, 620, 158.
26. P. C. Damiani, M. Bearzotti, M. A. Cabezón and A. C. Olivieri, J. Pharm. Biomed. Anal., 1999, 20, 587.
27. A. E. Martell and R. J. Motekaitis, The Determination and Use of Stability Constants, VCH, New York, 2nd. edn., 1992.
28. R. J. Motekaitis and A. E. Martell, Can. J. Chem., 1982, 60, 2403.
29. A. C. Olivieri and G. M. Escandar, Anal. Lett., 1997, 30, 1967.
30. G. A. Ibañez, A. C. Olivieri and G. M. Escandar, J. Chem. Soc., Faraday Trans., 1997, 93, 545.
31. C. L. Araujo, G. A. Ibañez, G. N. Ledesma, G. M. Escandar and A. C. Olivieri, Comput. Chem., 1998, 22, 161.
32. A. E. Martell and R. M. Smith, Critical Stability Constants, Plenum Press, New York, 1977, vol. 3, p. 13.
33. K. A. Connors and J. M. Lipari, J. Am. Chem. Soc., 1976, 3, 379.
34. S. G. Schulman, in Modern Fluorescence Spectroscopy ed. E. L. Wehry, Plenum Publishing Corporation, New York, 1976, vol. 2, ch. 6, p. 266.
35. S. G. Schulman and L. S. Rosenberg, J. Phys. Chem., 1979, 83, 447.
36. R. F. Chen, in Practical Fluorescence, ed. G. G. Guilbaut, Marcel Dekker, New York, 2nd edn., 1990, ch. 11, p. 618.
37. S. G. Schulman, R. M. Threatte, A. C. Capomacchia and W. L. Paul, J. Pharm. Sci., 1974, 63, 876.
38. J. M. Schuette, T. Ndou, A. Muñoz de la Peña, K. L. Greene, C. K. Williamson and I. M. Warner, J. Phys. Chem., 1991, 95, 4897.
39. M. J. S. Dewar, E. G. Zoebisch, E. F. Healy and J. J. P. Stewart, J. Am. Chem. Soc., 1985, 107, 3902.
40. British Pharmacopoeia, H. M. Stationery Office, London, 1998, p. 402.
41. A. Skoog, Principles of Instrumental Analysis, Saunders College Publishing, Philadelphia, 3rd edn., 1985, p. 22.
42. Cuadros Rodríguez, A. M. García Campaña, C. Jimenez Linares and M. Román Ceba, Anal. Lett., 1993, 26, 1243.
43. D. Winefordner and G. L. Long, Anal. Chem., 1983, 55, 712.