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.

Improvement of solubility and stability of valsartan by hydroxypropyl-beta-cyclodextrin

CAPPELLO, BRUNELLA;IERVOLINO, MARIA;MIRO, AGNESE
2006

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.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11588/101520
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