Solubilization of a naphthoquinone derivative by hydroxypropyl-beta-cyclodextrin (HP-beta-CD) and polyvinylpyrrolidone (PVP-K30). The influence of PVP-K30 and pH on solubilizing effect of HP-beta-CD.
The effects of hydroxypropyl-beta-cyclodextrin (HP-beta-CD) and Polyvinylpyrrolidone (PVP-K30) on the solubility of 2-Hydroxyl-N-(3-methyl-5-ethylisoxazolyl-4-yl)-1,4-naphthoquinone-4-imine (I) were investigated, this compound, a synthetic derivative of isoxazolylnaphthoquinones, has proved to exhibit important biological activity against the causative agent of Chagas' disease and against Staphylococcus aureus. In addition, the effect of co-administration of a water-soluble polymer (PVP-K30) and ionization of I on the HP-beta-CD solubilizing effect was also examined. HP-beta-CD and PVP-K30 possess a significant solubilizing effect by themselves. PVP-K30 increases the solubilizing effect of HP-beta-CD by enhancing the apparent stability constant (Kc) of the I: HP-beta-CD complex. The addition of 0.5% (w/v) PVP-K30 to the complexation medium results in a 83% increase in the stability constant of the complex. The HP-beta-CD solubilization of I can also be improved by ionization of the drug molecule through pH adjustments. Although the Kc of the I complex is larger in the neutral form, a higher overall solubility is attained when I is in its ionized form. A 38-fold solubility enhancement is possible by using a combined approach of pH adjustment and complexation with HP-beta-CD.
Granero
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G
Departamento de Farmacia, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ciudad Universitaria, 5000-Córdoba, Argentina.
de Bertorello
M M
MM
Longhi
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M
D000073738:2-Hydroxypropyl-beta-cyclodextrin; D003505:Cyclodextrins; D006863:Hydrogen-Ion Concentration; D007202:Indicators and Reagents; D009285:Naphthoquinones / Q000737:chemistry*; D011205:Povidone; D012995:Solubility; D047392:beta-Cyclodextrins
D003505:Cyclodextrins; D007202:Indicators and Reagents; D009285:Naphthoquinones; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D011205:Povidone