INVESTIGADORES
LONGHI Marcela Raquel
artículos
Título:
Effect of Hydroxypropyl-b-cyclodextrin on the Solubility of a Naphthoquinone-imine
Autor/es:
LINARES MARCELA, BERTORELLO MARÍA, AND LONGHI MARCELA
Revista:
INTERNATIONAL JOURNAL OF PHARMACEUTICS
Editorial:
Elsevier Science
Referencias:
Lugar: Oxford, UK; Año: 1997 vol. 159 p. 13 - 18
ISSN:
0378-5173
Resumen:
The effects of the hydroxypropyl-ß-cyclodextrin (HPCD) on the solubility of 2-hydroxy-N-(5-methyl-3-isoxazolyl)-1,4-naphthoquinone-4-imine (I) were investigated. I is an experimental drug for the treatment of cancer which exhibits low water solubility and it is therefore difficult to prepare the solutions for biological tests. The presence of an ionisable hydroxyl moiety (pKa = 5.80) increases the solubility via pH adjustment, but only a solubility of 0.124 mg/ml was obtained at pH 8.00. I was found to form inclusion complexes in either its neutral or its anionic form with HPCD. Although the stability constant of the I complex is larger in the neutral form, a greater overall solubility is obtained when I is in its ionised form. A 270-fold solubility enhancement is possible by using a combined approach of pH adjustment and complexation with HPCD.
