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Physicochemical study of solid-state benznidazole–cyclodextrin complexes

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Abstract

Although not being the ideal drug due to its low solubility and high toxicity, the benznidazole is the drug currently chosen for Chagas disease treatment. The deep knowledge about the characteristics of the drug in addition to the knowledge of more effective vectorization techniques of drugs in pharmaceutical forms allows a faster and cheaper development of a new therapeutic alternative in comparison to the introduction of a new molecule in the treatment. The aim of this study is the characterization of inclusion complexes Benznidazole and cyclodextrins in solid state. The interactions between Benznidazole (BNZ) and β-cyclodextrins (β-CD) modified: randomly methylated β-CD (RMβCD) and sulfobutylether β-CD (SBβCD) were studied by differential scanning calorimetry (DSC), fourier transform-infrared spectroscopy, RAMAN, and scanning electron microscopy. The preparation of solid-state binary systems by different techniques, namely, kneading, evaporated, and freeze-drying. The results suggest the formation of inclusion complexes of the drug with both CDs types in solid state by the techniques which were used, based on physicochemical data of interaction compared to the drug or the CDs/drug physical mixture. Thus, the preparation technique played an important role in the BNZ and modified CDs.

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References

  1. Coura JR, Castro SL. A critical review on chagas disease chemotherapy. Mem Inst Oswaldo Cruz. 2002;97:03–24.

    Article  CAS  Google Scholar 

  2. Lamas MC, Villagi L, Nocito I, Bassani G, Leonardi D, Pascutti F, Serra E, Salomón CJ. Development of parenteral formulations and evaluations of the biological activity of the trypanocide drug benznidazole. Int J Pharm. 2006;307:239–43.

    Article  CAS  Google Scholar 

  3. Docampo R. Recent developments in the chemotherapy of Chagas disease. Curr Pharm Des. 2001;7:1157–64.

    Article  CAS  Google Scholar 

  4. Morilla MJ, Montanari JA, Prieto MO, Lopez MO, Petray PB, Romero EL. Intravenous liposomalbenznidazole as trypanocidal agent: increasing drug delivery to liver is not enough. Int J Pharm. 2004;278:311–8.

    Article  CAS  Google Scholar 

  5. Silva-Nogueira S, Jerley J, Pavanelli WR, Gutierrez FRS, Lima FCA, Silva ABF, Silva SJ, Franco WD. Complexation of the anti-Trypanosoma cruzi drug benznidazole improves solubility and efficacy. J Med Chem. 2008;51:4104–14.

    Article  Google Scholar 

  6. Jung J, Yoo S, Lee S, Kim K, Yoon D, Lee K. Enchanced solubility and dissolution rates of itraconazole by a solid dispersion technique. Int J Pharm. 1999;187:195–201.

    Article  Google Scholar 

  7. Akkar A, Muller RH. Intarvenous itraconazole emulsions produced by solemuls technology. Eur J Pharm Biopharm. 2003;56:29–36.

    Article  CAS  Google Scholar 

  8. Figueiras A, Carvalho RA, Ribeiro L, Torres-Labandeira JJ, Veiga FJB. Solid-state characterization and dissolution profiles of the inclusion complexes of omeprazole with native and chemically modified β-cyclodextrin. Eur J Pharm Biopharm. 2007;67:531–9.

    Article  CAS  Google Scholar 

  9. Rodriguez-Tenreiro C, Alvarez-Lorenzo C, Concheiro A, Torres-Labandeira JJ. Characterization of cyclodextrin–carbopol interactions by DSC and FTIR. J Therm Anal Calorim. 2004;77:403–11.

    Article  CAS  Google Scholar 

  10. Piel G, Pirotte B, Delneuville I, Neven P, Llabres G, Delarge J, Delattre L. Study of the influence of both cyclodextrins and l-lysine on the aqueous solubility of nimesulide; isolation and characterization of nimesulide-l-lysine–cyclodextrin complexes. J Pharm Sci. 1997;86:475–80.

    Article  CAS  Google Scholar 

  11. Ventura CA, Giannone I, Paolino D, Pistara V, Corsaro A, Puglisi G. Preparation of celecoxib-dimethyl-b-cyclodextrin inclusion complex: characterization and in vitro permeation study. Eur J Med Chem. 2005;40:624–31.

    Article  CAS  Google Scholar 

  12. Bruni G, Milanese C, Berbenni V, Sartor F, Villa M, Marini A. Crystalline and amorphous phases of a new drug. J Therm Anal Calorim. 2010;102:297–303.

    Article  CAS  Google Scholar 

  13. Pinto MF, Moura EA, Souza FS, Macêdo RO. Thermal compatibility studies of nitroimidazoles and excipients. J Therm Anal Calorim. 2010;102:323–9.

    Article  CAS  Google Scholar 

  14. Soares-Sobrinho JL, Silva ALM, Grangeiro-Júnior S, Medeiros FPM, Rolim-Neto PJ. Desenvolvimento e validação do método analítico para o doseamento de benznidazol. Rev Bras Farm. 2006;87:78–80.

    CAS  Google Scholar 

  15. Lipkowitz KB. Applications of computational chemistry to the study of cyclodextrins. Chem Rev. 1998;5:1829–73.

    Article  Google Scholar 

  16. Pose-Vilarnovo B, Perdomo-Lopez I, Echezarreta-Lopez M, Schroth-Pardo P, Estrada E, Torres-Labandeira JJ. Improvement of water solubility of sulfamethizole through its complexation with b- and hydroxypropyl-b-cyclodextrin. Characterization of the interaction in solution and in solid state. Eur J Pharm Sci. 2001;13:325–31.

    Article  CAS  Google Scholar 

  17. Hedges AR. Industrial applications of cyclodextrins. Chem Rev. 1998;98:2035–44.

    Article  CAS  Google Scholar 

  18. Okimoto K, Rajewski RA, Uekama K, Jona JA, Stella VJ. The interaction of charged and uncharged drugs with neutral (HP-beta-CD) and anionically charged (SBE7-beta-CD) beta-cyclodextrins. Pharm Res. 1996;13:256–64.

    Article  CAS  Google Scholar 

  19. Fernandes CM, Vieira TM, Veiga FJB. Physicochemical characterization and in vitro dissolution behavior of nicardipine–cyclodextrins inclusion compounds. Eur J Pharm Sci. 2002;15:79–88.

    Article  CAS  Google Scholar 

  20. Cirri M, Rangoni C, Maestrelli F, Corti G, Mura P. Development of fast-dissolving tablets of flurbiprofen–cyclodextrin complexes. Drug Dev Ind Pharm. 2005;31:697–707.

    Article  CAS  Google Scholar 

  21. Soares-Sobrinho JL, Cunha-Filho MSS, Rolim-Neto PJ, Torres-Labandeira JJ, Dacunha-Marinho B. Benznidazole. Acta Cryst. 2008;E64:o634.

    CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, Federal University of Pernambuco, Arthur de Sá, s/n, 50740-521, Recife, PE, Brazil

    José Lamartine Soares-Sobrinho & Monica Felts de La Roca Soares

  2. Core of Pharmaceutical Technology, Federal University of Piauí, Campus Universitário Ministro Petrônio Portella, s/n, 64049-550, Teresina, PI, Brazil

    José Lamartine Soares-Sobrinho, Monica Felts de La Roca Soares & Pedro José Rolim-Neto

  3. Department of Pharmacy and Pharmaceutical Technology, Facultad de Farmacia, Universidad de Santiago de Compostela, 15782, Santiago de Compostela, Spain

    Juan J. Torres-Labandeira

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  1. José Lamartine Soares-Sobrinho
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  2. Monica Felts de La Roca Soares
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  3. Pedro José Rolim-Neto
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  4. Juan J. Torres-Labandeira
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Correspondence to José Lamartine Soares-Sobrinho.

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Soares-Sobrinho, J.L., de La Roca Soares, M.F., Rolim-Neto, P.J. et al. Physicochemical study of solid-state benznidazole–cyclodextrin complexes. J Therm Anal Calorim 106, 319–325 (2011). https://doi.org/10.1007/s10973-010-1186-x

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  • DOI: https://doi.org/10.1007/s10973-010-1186-x

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