Abstract
Aim of the present work was to investigate the effect of hydroxypropyl-β-cyclodextrin (HP-β-CD) on the solubility, dissolution rate and stability of Valsartan (VAL), a drug used orally for the treatment of hypertension. Phase solubility studies demonstrated the ability of the HP-β-CD to complex VAL and to increase drug solubility. The dissolved amount of VAL increased linearly with the addition of HP-β-CD according to an AL type plot. The apparent stability constant of the complex, calculated supposing a 1:1 stoichiometry, was 296±7 M−1. VAL/HP-β-CD interactions were also studied by 13C-NMR spectroscopy. Equimolar VAL/HP-β-CD solid systems were prepared by physical-mixing and freeze-drying, and their properties in the solid state studied by DSC and FT-IR analysis. The results provided clear indications of the formation of a new solid phase corresponding to the inclusion complex in the freeze-dried sample. The dissolution profiles of the drug from each solid system were affected by its physico-chemical properties, the freeze-dried being the most rapidly dissolving form. The thermal stability of the complex was studied, also determining the number and identity of the decomposition products of the drug. The stability studies revealed that the VAL/HP-β-CD complex significantly decreases the rate of VAL degradation. These results suggest that CD technology would be a very useful method to overcome the solubility and the stability problems of VAL.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
L. Criscione, M. De Gasparo, P. Buehlmayer, S. Whitebread, H.P. Ramjouè, J.M. Wood, (1993) Br. J. Pharmacol. 110:761
R. Dina, M. Jafari, 2000 Am. J. Health-Syst. Pharm. 57:1231
G. Flesch, P. Müller, P. Lloyd, 1997 Eur. J. Clin. Pharmacol. 52:115
T. Loftsson, M.E. Brewster, 1996 J. Pharm. Sci. 85:1117
K. Uekama, F. Hirayama, T. Irie, 1998 Chem. Rev. 98:2045
T. Higuchi, K.A. Connors, 1965 Adv. Anal. Chem. Instrum. 4:117
Y. Inoue, 1993 Ann. Rep. NMR Spectros. 27:59
K.H. Kim, M.J. Frank, N.L. Henderson, 1985 J. Pharm. Sci. 74:283
P. Mura, G.P. Bettinetti, A. Manderioli, M.T. Faucci, G. Bramanti, M. Sorrenti, 1998 Int. J. Pharm. 166:189
P. Mura, M.T. Faucci, P.L. Parrini, S. Furlanetto, S. Pinzauti, 1999 Int. J. Pharm. 179:117
Y. Nakai, K. Yamamoto, K. Terada, K. Akimoto, 1984 Chem. Pharm. Bull. 32:685
O.I. Corrigan, T. Stanley, 1982 J. Pharm. Pharmacol. 34:621
B. Cwiertnia, T. Hladon, M. Stobiecki, 1999 J. Pharm. Pharmacol. 51:1213
H.H. Tønnesen, 2001 Int. J. Pharm. 225:1
Acknowledgement
This work was kindly supported by a grant from MIUR (PRIN 2004).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
CAPPELLO, B., MAIO, C.D., IERVOLINO, M. et al. Improvement of Solubility and Stability of Valsartan by Hydroxypropyl-\boldbeta-Cyclodextrin. J Incl Phenom Macrocycl Chem 54, 289–294 (2006). https://doi.org/10.1007/s10847-005-9004-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10847-005-9004-y