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Combination of phase-solubility method and capillary zone electrophoresis to determine binding constants of cyclodextrins with practically water-in…

A new interesting article has been published in J Pharm Biomed Anal. 2018 Oct 25;160:12-18. doi: 10.1016/j.jpba.2018.07.038. Epub 2018 Jul 21. and titled:

Combination of phase-solubility method and capillary zone electrophoresis to determine binding constants of cyclodextrins with practically water-in…

Authors of this article are:

Sursyakova VV, Maksimov NG, Levdansky VA, Rubaylo AI.

A summary of the article is shown below:

The combined method based on phase-solubility technique and capillary zone electrophoresis (PS-CZE) was suggested for the determination of binding (stability) constants of cyclodextrins (CD) complexes with water-insoluble organic compounds that have no or weak UV chromophores. In this method, the insoluble compounds are agitated at the desired temperature in CD solutions with different concentration up to the attainment of equilibrium and then CZE is used to determine the concentration of the compounds that have passed into the solutions. To avoid precipitation and complex dissociation, the background electrolyte (BGE) for CZE should contain ethanol and, if necessary, cyclodextrin. The samples should be diluted with the BGE without CD so that the CD concentrations in BGE and samples were equal to preclude a baseline shift. Using the suggested approach, the inclusion complexes between betulinic and betulonic acids, pentacyclic lupane-type triterpenes, and hydroxypropyl-β- and γ-cyclodextrins (HP-β-CD and HP-γ-CD) were studied. It was found that solubility of the acids studied in HP-β-CD solutions did not differ from their solubility in pure water. That is, the HP-β-CD complexes of the acids studied were not formed in noticeable amount. At the same time, the acids formed inclusion complexes with HP-γ-CD, what possibly was caused by the greater size of the HP-γ-CD molecule as compared to HP-β-CD. To determine binding constants by Higuchi and Connors method, the acids solubility was determined by CZE after their agitation in the solutions of HP-γ-CD (with 0.6 molar substitution) at 25 °C for 3 days. The dependences of acids solubility on HP-γ-CD concentration deviated from straight line in the range of high concentration (AN mode). This can be explained by a self-association of HP-γ-CD molecules. Using the linear segment of the solubility dependences on CD concentration, the binding constants were determined. Their logarithms for the HP-γ-CD complexes with betulonic and betulinic acids were 3.88 ± 0.14 and 3.82 ± 0.12, respectively.

Check out the article’s website on Pubmed for more information:



This article is a good source of information and a good way to become familiar with topics such as:

Betulin derivatives;Drug delivery;Hydroxypropyl-γ-cyclodextrin;Inclusion complexes;Kinetically inert complexes;Solubilization

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