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Drug Solubilization by Mixtures of Cyclodextrins: Additive and Synergistic Effects
Molecular Pharmaceutics ( IF 4.9 ) Pub Date : 2019-01-04 00:00:00 , DOI: 10.1021/acs.molpharmaceut.8b00953
Christian Schönbeck 1 , Karina Gaardahl 1 , Bryan Houston 1
Affiliation  

Cyclodextrins are popular drug solubilizers, but the use of the natural cyclodextrins is hampered by their tendency to coprecipitate with the drug. To understand and overcome such problems, we have studied the solubility of dexamethasone in the presence of natural β-cyclodextrin and γ-cyclodextrin, individually and in various combinations. Equilibrium models of the phase-solubility diagrams with individual cyclodextrins revealed that dexamethasone was solubilized as 1:1 complexes, but formation of insoluble higher-order complexes set an upper limit to the concentration of solubilized dexamethasone. This limit could be raised from 8 to 17 mM by using combinations of the two cyclodextrins, as their solubilizing properties were additive in some regions of the phase-solubility diagram and synergistic in other regions. The additive effects arise from the additivity of solubilities—the same phenomenon contributes to the good solubilizing properties of many modified cyclodextrins. The synergistic effects, however, could not be explained. The results open up for an increased use of the natural cyclodextrins as an improved alternative to modified cyclodextrins.

中文翻译:

药物由环糊精的混合物溶解:加和协同作用。

环糊精是流行的药物增溶剂,但是由于天然环糊精与药物共沉淀的趋势而妨碍了它们的使用。为了理解和克服这些问题,我们研究了地塞米松在天然β-环糊精和γ-环糊精存在下的溶解度,分别以各种组合形式进行研究。与各个环糊精的相溶度图平衡模型显示,地塞米松可溶解为1:1的配合物,但不溶性高阶配合物的形成为可溶解的地塞米松的浓度设定了上限。通过将两种环糊精结合使用,该极限值可以从8 mM提高到17 mM,因为它们的增溶性能在相溶度图中的某些区域是累加的,而在其他区域是协同的。加性效应是由溶解性的加性产生的-同样的现象也有助于许多改性环糊精的良好溶解性能。然而,协同效应无法解释。该结果为增加天然环糊精作为改性环糊精的改良替代物的使用开辟了道路。
更新日期:2019-01-04
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