Granero G, de Bertorello M M, Longhi M
Departamento de Farmacia, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ciudad Universitaria, 5000-Córdoba, Argentina.
Boll Chim Farm. 2002 Jan-Feb;141(1):63-6.
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.
研究了羟丙基-β-环糊精（HP-β-CD）和聚乙烯吡咯烷酮（PVP-K30）对2-羟基-N-（3-甲基-5-乙基异恶唑-4-基）-1,4-萘醌-4-亚胺（I）溶解度的影响。该化合物是异恶唑基萘醌的合成衍生物，已证明对恰加斯病病原体和金黄色葡萄球菌具有重要的生物活性。此外，还研究了水溶性聚合物（PVP-K30）的共同给药以及I的离子化对HP-β-CD增溶效果的影响。HP-β-CD和PVP-K30自身具有显著的增溶作用。PVP-K30通过提高I：HP-β-CD复合物的表观稳定常数（Kc）来增强HP-β-CD的增溶效果。向络合介质中添加0.5%（w/v）的PVP-K30可使复合物的稳定常数提高83%。通过调节pH使药物分子离子化也可以提高HP-β-CD对I的增溶作用。尽管I复合物的Kc在中性形式下较大，但当I处于离子化形式时可获得更高的总体溶解度。通过pH调节和与HP-β-CD络合的联合方法，溶解度可能提高38倍。
