Solubilization of naphthoquinones by complexation with hydroxypropyl-β-cyclodextrin

被引：27

作者：

Linares, M ^{[1
]}

de Bertorello, MM ^{[1
]}

Longhi, M ^{[1
]}

机构：

[1] Univ Nacl Cordoba, Fac Ciencias Quim, Dept Farmacia, RA-5000 Cordoba, Argentina

来源：

INTERNATIONAL JOURNAL OF PHARMACEUTICS | 1997年 / 159卷 / 01期

关键词：

charge effects; hydroxypropyl-beta-cyclodextrin; inclusion complexation; isoxazolylnaphthoquinoneimine; 1,2-naphthoquinone; solubility study;

D O I：

10.1016/S0378-5173(97)00269-X

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

The effects of the hydroxypropyl-beta-cyclodextrin (HPCD) on the solubility of 2-hydroxy-N-(5-methyl-3-isoxazoyl)-1,4-naphthoquinone-4-amine (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 ionizable hydroxyl moiety (pK(a) = 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 ionized form. A 270-fold solubility enhancement is possible by using a combined approach of pH adjustment and complexation with HPCD. (C) 1997 Elsevier Science B.V.

引用

页码：13 / 18

页数：6

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