Interaction Between Nitroheterocyclic Compounds With β-cyclodextrins: Phase Solubility And Hplc Studies

Chagas disease is a serious health problem for Latin America. Nitrofurazone (NF) and Hidroxymethylnitrofurazone (NFOH) are active against Trypanosoma cruzi. The effect of β-cyclodextrin (β-CD) and dimethyl-β-cyclodextrin (DM-β-CD) complexation on the UV absorption and retention time of nitrofurazone (NF) and its hydroxymethylated analog (NFOH) were studied in solution. The retention behavior was analyzed on a reversed phase C18 column and the mobile phase used was acetonitrile-water (20/80 v/v), in which cyclodextrins (β-CD or DM-β-CD) were incorporated as a mobile phase additive. The decrease in the retention times of NF (or NFOH) with increasing concentration of HP-β-CD enables the determination of the complex stability constants by HPLC. A phase-solubility study was performed, according to the method reported by Higuchi and Connors, to evaluate the changes of NF/NFOH in the complexation state, and the diagrams obtained suggested that it forms complexes with a stoichiometry of 1:1. This is an important study for the characterization of potential formulations to be used as therapeutic options for the treatment of Chagas disease. © 2008 Elsevier B.V. All rights reserved.474-5865869WHO, Chagas Disease: Strategic Direction for Research. Disease Burden and Epidemiological Trends, http://www.who.int/tdr/diseases/chagas/direction.htm, accessed in January 2007Coura, J.R., de Castro, S.L., (2002) Membr. Inst. Oswaldo Cruz, 97, pp. 3-24Dodd, M.C., Stillman, W.B., (1944) J. Pharmacol. Exp. Ther., 82, p. 11Henderson, G.B., Ulrich, P., Fairlamb, A.H., Rosenberg, I., Pereira, M., Sela, M., Cerami, A., (1998) Proc. Natl. Acad. Sci. U.S.A., 85, p. 5374A. Korolkovas, Dicionário Terapêutico Guanabara, Ed. (2000)/2001, Guanabara Koogan: Rio de Janeiro, 2002Chung, M.C., Guido, R.V.C., Martinelli, T.F., Gonçalves, M.F., Polli, M.C., Botelho, K.C.A., Varanda, E.A., Ferreira, E.I.F., (2003) Bioorg. Med. Chem., 11, pp. 4779-4783Szejtli, J., (1998) Cyclodextrin Technology, , Kluwer Academic Publishers, LondonDollo, G., Thompson, D.O., Le Corre, P., Chevanne, F., Le Verge, R., (1998) Int. J. Pharm., 164, pp. 11-19Szejtli, J., (1994) Med. Res. Rev., 14, pp. 353-386Shuang, S.M., Pan, J.H., Guo, S.Y., Cai, M.Y., Liu, C.S., (1998) Anal. Lett., 30, p. 2261Stella, V.J., Rajewski, R.A., (1997) Pharm. Res., 14, p. 556Melo, N.F., Grillo, R., Moraes, C.M., Brito, C.L., Trosssini, G.H.G., Menezes, C.M., Ferreira, E.I., Fraceto, L.F., (2007) Rev. Ciênc. Farm. Básica Apl., 28, p. 35Grillo, R., Melo, N.F., Brito, C.L., Trosssini, G.H.G., Menezes, C.M., Ferreira, E.I., Moraes, C.M., Fraceto, L.F., (2008) Quím. Nova, 31, pp. 290-295Atwood, J.L., Davies, J.E.D., Macnicol, D.D., Vögtle, F., (1996) Cyclodextrins, 3. , Szejtli J., and Osa T. (Eds), Elsevier Science Ltd., OxfordHiguchi, T., Connors, K.A., (1965) Adv. Anal. Chem. Inst., 4, pp. 117-212Loftsson, T., Hreinsdóttir, D., Másson, M., (2005) Int. J. Pharm., 302, pp. 18-28Loftsson, T., Vogensen, S.B., Brewster, M.E., Konrádsdóttir, F., (2007) J. Pharm. Sci., 10, pp. 2532-2546Uekama, K., Hirayama, F., Irie, T., (1978) Chem. Lett., p. 661Uekama, K., Hirayama, F., Nasu, S., Matsuo, N., Irie, T., (1978) Chem. Pharm. Bull., 26, pp. 3477-3484Ravelet, C., Geze, A., Villet, A., Grosset, C., Ravel, A., Wouessid-jewe, D., Peyrin, E., (2002) J. Pharm. Biomed. Anal., 29, pp. 425-430Moraes, C.M., Abrami, P., de Paula, E., Braga, A.F., Fraceto, L.F., (2007) Int. J. Pharm., 331, pp. 99-106Jullian, C., Moyano, L., Yañez, C., Olea-Azar, C., (2007) Spectrochim. Acta Part A, 67, pp. 230-234Chadha, R., Jain, D.V.S., Aggarwal, A., Singh, S., Thakur, D., (2007) Thermochim. Acta, 459, pp. 111-115Hamada, H., Ishihara, K., Masuoka, N., Mikuni, K., Nakajima, N., (2006) J. Biosci. Bioeng., 102, pp. 369-371Cabral Marques, H.M., Hadgraft, J., Kellaway, I.W., (1990) Int. J. Pharm., 63, pp. 259-266Gazpio, C., Sánchez, M., García-Zubiri, I.X., Vélaz, I., Martinez-Ohárriz, C., Martín, C., Zornoza, A., (2004) J. Pharm. Biomembr. Anal., 9, pp. 487-492Loftsson, T., Hreinsdóttir, D., Másson, M., (2007) J. Incl. Phenom. Macrocycl. Chem., 57, pp. 545-55