Improvement of Solubility and Stability of Valsartan by Hydroxypropyl-\boldbeta-Cyclodextrin

Journal of Inclusion Phenomena (Impact Factor: 1.43). 01/2006; 54(3):289-294. DOI: 10.1007/s10847-005-9004-y

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±7M−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.

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