Pharmaceutical Composition of Valsartan: β-Cyclodextrin: Physico–Chemical Characterization and Anti-Hypertensive Evaluation

Molecules

Carlos Eduardo De Matos Jensen¹  Robson Augusto Souza Dos Santos¹  Angelo Márcio Leite Denadai¹  Cynthia Fernandes Ferreira Santos¹  Aline Nardoni Gonçalves Braga¹ 

[1] ¹Departamento de Química, ICEx, Universidade Federal de Minas Gerais, Avenida Pres. Antônio Carlos 6627, 31270-901, Belo Horizonte, Brazil

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

DOI  :  10.3390/molecules15064067

来源: mdpi

【 摘 要 】

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.

【 授权许可】

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This is an open access article distributed under the Creative Commons Attribution License (CC BY) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.