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• De Matos Jensen, C
• Dos Santos, R
• Denadai, A
• Santos, C
• Braga, A
• Sinisterra, R
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• De Matos Jensen, C
• Dos Santos, R
• Denadai, A
• Santos, C
• Braga, A
• Sinisterra, R
• [+] on PubMed
• De Matos Jensen, C
• Dos Santos, R
• Denadai, A
• Santos, C
• Braga, A
• Sinisterra, R

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Molecules 2010, 15(6), 4067-4084; doi:10.3390/molecules15064067

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 Gonçalves Braga ²  and Rubén Dario Sinisterra ^1,*

¹ Departamento de Química, ICEx, Universidade Federal de Minas Gerais, Avenida Pres. Antônio Carlos 6627, 31270-901, Belo Horizonte, Brazil ² Departamento de Fisiologia e Biofísica, ICB, Universidade Federal de Minas Gerais, 31270-901 Belo Horizonte, Brazil ³ Campus Centro Oeste Dona Lindu, Universidade Federal de São João del Rei, R. Sebastião Gonçalves Coelho, 400, 35501-296, Divinópolis, Brazil

* Author to whom correspondence should be addressed.

Received: 17 May 2010 / Accepted: 27 May 2010 / Published: 4 June 2010

Download PDF Full-Text [2312 KB, uploaded 4 June 2010 17:34 CEST]

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 analysis showed A_L-type diagrams with β-cyclodextrin (β-CD). Microcalorimetric titrations suggested the formation of 1:1 inclusion complex between VAL and β-CD. The apparent stability constants K_1:1 calculated from phase-solubility plots were 165.4 M^-1 (298 K), 145.0 M^-1 (303 K) and 111.3 M^-1 (310 K). In vivo experiments in rats showed that reduction in arterial pressure for the FDY complex is better than with valsartan used alone. The better activity of FDY can be attributed to the higher solubility of valsartan after inclusion in the cyclodextrin cavity, as suggest by the intrinsic dissolution studies.

Keywords: valsartan; β-cyclodextrin; intrinsic dissolution; ROESY; anti-hypertensive evaluation

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