Preparation And Initial Characterization Of Inclusion Complex Between Nitrofurazone And 2-hydroxypropyl-β-cyclodextrin [preparação E Caracterização Inicial De Complexo De Inclusão Entre Nitrofurazona E 2-hidroxipropil-β-ciclodextrina]

Nitrofurazone (NF), 5-nitro-2-furaldehyde semicarbazone, a broad-spectrum antibiotic, has reported toxic effects and low solubility in water. It would be of great interest to form inclusion complexes between NF and a cyclodextrin, to develop more effective and safer antibiotic formulations. This paper focuses on the preparation of inclusion complexes of NF with 2-hydroxypropyl-β- cyclodextrin (HP-β-CD) and their initial characterization by evaluating rates of complex formation, photostability, solubility isotherms, release rate profiles, stoichiometry of the complexes and their morphology, as revealed by scanning electron microscopy. The kinetic tests of complex formation revealed that 17,3 h is enough for stabilization of the NF-cyclodextrin complex. The solubility isotherm studies showed that the isotherm changes from type A to type B, as a function of temperature. The photostability experiments showed that the insertion of the NF in the HP-β-CD cavity protects the drug from photodecomposition. The release kinetic tests showed that the profile of NF release from the complex is altered by the presence of HP-β-CD in the medium. A Job's plot indicated that the stoichiometry of the complex was 1:1 NF:HP-β-CD. The scanning electron micrographs showed changes in the crystal structure of NF in the complex. This study focused on the physicochemical properties of drug-delivery formulations that could potentially be developed into a novel type of therapy with NF.2813544Amidon, G.L., Lennernas, H., Shah, V.P., Crison, J.R., A theoretical basis for a biopharmaceutic drug classification: The correlation of in vitro drug product dissolution and in vivo bioavailability (1995) Pharm Res, 12, pp. 413-420Araújo, D.R., Pinto, L.M.A., Braga, A.F.A., de Paula, E., Drug-delivery systems for local anesthetics:therapeutic applications (2003) Rev Bras Anestesiol, 53, pp. 663-671Azevedo, M.B.M., Alderete, J.B., Rodriguez, J.A., Souza, A.O., Rettori, D., Torsoni, M.A., Faljoni-Alario, A., Duran, N., Biological activities of violacein, a new antitumoral indole derivative, in an inclusion complex with β-Cyclodextrin (2000) J Incl Phenom Macrocycl Chem, 37, pp. 93-101Bayomi, M.B., Abanumay, K.A., Al-Angary, A.A., Effect of inclusion complexation with cyclodextrins on photostability of nifedipine in solid state (2002) Int J Pharm, 243, pp. 107-117Bekers, O., Uijtendaal, E.V., Beijnen, J.H., Bult, A., Underberg, W.J.M., Cyclodextrins in the pharmaceutical field (1991) Drug Dev Ind Pharm, 17, pp. 1503-1549Chen, C.C., Chen, F.A., Wu, A., Hsu, H., Kang, J., Cheng, H., Effect of hydroxypropyl-β-cyclodextrin on the solubility, photostability and in-vitro permeability of alkannin/shikonin enantiomers (1996) Int J Pharm, 141, pp. 171-178Connors, K.A., The stability of cyclodextrin complexes in solution (1997) Chem Rev, 97, pp. 1325-1358Del Valle, E.M.M., Cyclodextrins and their uses: A review (2004) Process Biochem, 39, pp. 1033-1046Dodd, M.C., Stillman, W.B., The in vitro bacteriostatic action of some simple furan derivatives (1944) J Pharmacol Exp Ther, 82, pp. 11-18Etos, S., Noda, H., Noda, A.J., Simultaneous determination of antiepileptic drugs and their metabolites, including chiral compounds, via beta-cyclodextrin inclusion complexes by a column-switching chromatographic technique (1994) J Chromatogr B, 19, pp. 385-390Flood, K.G., Reynolds, E.R., Snow, N.H., Characterization of inclusion complexes of betamethasone-related steroids with cyclodextrins using high-performance liquid chromatography (2000) J Chromatogr A, 903, pp. 49-65Gonçalves, M.F., Chung, M.C., Colli, W., Miranda, M.T.M., Ferreira, E.I., Efeito da associação da nitrofurazona e primaquina em células LLC-MK2 infectadas com formas tripomastigotas de Trypanossoma cruzi. (1994) Rev Soc Bras Med Trop, 27, p. 164Henderson, G.B., Ulrich, P., Fairlamb, A.H., Rosemberg, I., Pereira, M., Sela, M., Cerami, A., Subversive substrates for the enzyme trypanothione disulphide reductase, alternative approach to chemoterapy of Chagas disease (1988) Proc Natl Acad Sci, 85, pp. 5374-5378Irie, T., Uekama, K., Pharmaceutical applications of ciclodextrins. III. Toxicological issues and safety evaluation (1997) J Pharm Sci, 86, pp. 147-162Ivanov, P.M., Salvatierra, D., Jaime, C., Experimental (NMR) and Computational (MD) Studies on the Inclusion Complexes of 1-Bromoadamantane with alpha-, beta-, and gamma-Cyclodextrin (1996) J Org Chem, 61, pp. 7012-7017Laverde Jr, A., Conceição, G.J.A., Queiroz, S.C.N., Fujiwara, F.Y., Marsaioli, A.J., An NMR tool for cyclodextrin selection in enantiomeric resolution by high-performance liquid (2002) Magn Reson Chem, 40, pp. 433-442Loftsson, T., Masson, M., Cyclodextrins in topical drug formulations: Theory and practice (2001) Int J Pharm, 225, pp. 15-30Loukas, Y.L., Vraka, V., Gregoriadis, G., Drugs in cyclodextrins, in liposomes: A novel approach to the chemical stability of drugs sensitive to hydrolysis (1998) Int J Pharm, 162 (2), pp. 137-142Másson, M., Loftsson, T., Másson, G., Stefánsson, E., Cyclodextrins as permeation enhancers: Some theoretical evaluations and in vitro testing (1999) J Control Release, 59 (1), pp. 107-118Matioli, G., (2000) Ciclodextrinas e suas aplicações em alimentos, fârmacos, agricultura, biotecnologia, química analítica e produtos gerais, , Maringá: Eduem Editora;, 124pMcCormack, B., Gregoriadis, G., Drugs-in-cyclodextrins-inliposomes: An approach to controlling the fate of water insoluble drugs in vivo (1998) Int J Pharm, 162, pp. 59-69Mielcarek, J., Daczkowska, E., Photodegradation of inclusion complexes of isradipine with methyl-beta-cyclodextrin (1999) J Pharm Biomed Anal, 21 (2), pp. 393-398Mielcarek, J., Effect of hydroxypropyl-β-cyclodextrin on the solubility, photostability and in-vitro permeability of alkannin/shikonin enantiomers (1994) Int J Pharm, 141, pp. 171-178Moraes, C.M., Abrami, P., Gonçalves, M.M., Andreo-Filho, N., Fernandes, S.A., de Paula, E., Fraceto, L.F., Preparação e caracterização físico-química de complexos de inclusão entre anestésicos locais e hidroxipropil - ciclodextrina. (2007) Quím Nova, 30, pp. 777-784Morin, N., Guillaume, Y.C., Peyrin, E., Rouland, J.C., Peculiarities of an imidazole derivative retention mechanism in reversed-phase liquid chromatography: β-cyclodextrin concentration and temperature considerations (1998) J Chromatogr A, 808, pp. 51-60Nichols, W., Antiinfecciosos (2004) Remington, , Ed, a ciência e a prática da farmácia. Rio de Janeiro: Guanabara Koogan;Paavola, A., Yliruusi, J., Kajimoto, Y., Kalso, E., Wahlström, T., Rosenberg, P., Controlled release of lidocaine from injectable gels and efficacy in rat sciatic nerve block (1995) Pharm Res, 12, pp. 1997-2002Pinto, L.M.A., Fraceto, L.F., Santana, M.H., Pertinhez, T.A., Oyama-Junior, S., de Paula, E., Physico-chemical characterization of benzocaine-beta-cyclodextrin inclusion complexes (2005) J Pharm Biomed Anal, 39, pp. 956-963Pomponio, R., Gotti, R., Fiori, J., Cavrini, V., Mura, P., Cirri, M., Maestrelli, F., Studies of curcumin and curcuminoids. XXVII. Cyclodextrin complexation: Solubility, chemical and photochemical stability (2003) Int J Pharm, 244, pp. 127-135Race, P.R., Lovering, A.L., Green, R.M., Ossor, A., White, S.A., Searle, P.F., Wrighton, C.J., Hyde, E.L.J., Structural and mechanistic studies of Escherichia coli nitroreductase with the antibiotic nitrofurazone. Reversed binding orientations in different redox states of the enzyme (2005) J Biol Chem, 280, pp. 13256-13264Stalcup, A.M., Chang, S.S., Armstrong, D.W., Pitha, J.J., (S)-2-hydroxypropyl-beta- cyclodextrin, a new chiral stationary phase for reversed-phase liquid chromatography (1990) J Chromatogr A, 513, pp. 181-194Thomas, G., Solubilidade dos fármacos (2003) Química medicinal: Uma introdução, , Rio de Janeiro: Guanabara Koogan;, 345pTong, W.Q., Lach, J.L., Chin, T.F., Guillory, J.K., Microcalorimetric investigation of the complexation between 2-hydroxypropyl-beta-cyclodextrin and amine drugs with the diphenylmethyl functionality (1991) J Pharm Biomed Anal, 9, pp. 1139-1146Yap, K.L., Liu, X., Thenmozhiyal, J.C., Ho, P.C., Photostability studies on nicardipine-cyclodextrin complexes by capillary electrophoresis (2004) J Pharm Biomed Anal, 35, pp. 267-27