Pharmaceutical Composition of Valsartan β-Cyclodextrin Physico–Chemical Characterization and Anti-Hypertensive Evaluation 英文参考文献.docVIP

Molecules 2010, 15, 4067-4084; doi:10.3390/molecule OPEN ACCESS molecules ISSN 1420-3049 /journal/molecules Article Pharmaceutical Composition of Valsartan: β-Cyclodextrin: Physico–Chemical Characterization and Anti-Hypertensive Evaluation Carlos Eduardo de Matos Jensen 1,3, Robson Augusto Souza dos Santos 2, Angelo Márcio Leite Denadai 1, Cynthia Fernandes Ferreira Santos 2, Aline Nardoni Gon?alves Braga 2 and Rubén Dario Sinisterra 1,* 1 Departamento de Química, ICEx, Universidade Federal de Minas Gerais, Avenida Pres. Ant?nio Carlos 6627, 31270-901, Belo Horizonte, Brazil; E-Mail: cej.jensen@ (C.E.M.J.) 2 Departamento de Fisiologia e Biofísica, ICB, Universidade Federal de Minas Gerais, 31270-901 Belo Horizonte, Brazil; E-Mails: robsonsant@ (R.A.S.); cynthiaff.santos@.br (C.F.F.S.); losartan04@.br (A.N.G.B) 3 Campus Centro Oeste Dona Lindu, Universidade Federal de S?o Jo?o del Rei, R. Sebasti?o Gon?alves Coelho, 400, 35501-296, Divinópolis, Brazil * Author to whom correspondence should be addressed; E-Mail: sinisterra@ufmg.br; Tel.: +55 31 3409 5778; Fax: +55 31 3409 5700. Received: 17 May 2010 / Accepted: 27 May 2010 / Published: 4 June 2010 Abstract: Valsartan, a water-insoluble drug, is mainly used in the treatment of hypertension albeit with reduced oral bioavailability. The aim of work was to develop a valsartan:β-cyclodextrin (VAL:β-CD) pharmaceutical composition in order to improve its water solubility and bioavailability. The VAL:β-CD complexes were prepared by the kneading, solid dispersion and freeze-drying methods, of which the freeze-drying method (FDY) was found to be the best to prepare an inclusion complex. A physical mixtyure PM was also prepared. Complexes were characterized by thermal analysis, Fourier transformed- infrared (FTIR) spectroscopy, Powder X-ray diffractometry, intrinsic dissolution and NMR (2D-ROESY). Phase-solubility analysi