alexa High-throughput phase-distribution method to determine drug-cyclodextrin binding constants.
Chemical Engineering

Chemical Engineering

Journal of Chromatography & Separation Techniques

Author(s): Chen Z, Lu D, Weber SG

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Abstract A high-throughput method has been developed to measure drug-cyclodextrin binding constants. It measures the distribution ratio of a drug between a polymer film [polyvinyl chloride (PVC) with 67\% (w/w) dioctyl sebacate (DOS)] and a cyclodextrin-containing buffer in a 96-well format. Measurements of distribution ratios at several cyclodextrin concentrations lead to binding constants. Binding constants for econazole with six CDs have been determined in one 96-well microplate with four replications of each condition in 10 h. The K(1:1)/10(3) M(-1) values are 3.98 +/- 0.13, 3.90 +/- 0.22, 29.3 +/- 2.2, 0.66 +/- 0.04, 1.78 +/- 0.30, 4.08 +/- 0.50, with (2-hydroxyethyl)-beta-cyclodextrin, (2-hydroxypropyl)-beta-cyclodextrin, 2,6-di-O-methyl-beta-cyclodextrin, heptakis(2,3,6-tri-O-methyl)-beta-cyclodextrin, alpha-cyclodextrin, beta-cyclodextrin, respectively. It is likely that 1:2 complexes are also formed in some cases. This method has also been applied to study the binding behavior as a function of the drug concentration and pH. Binding weakens at higher drug concentration which may be due to the self-association of the drug. An acidic environment decreases the binding constant of CD with the basic econazole. The formation of the 1:2 complexes is completely suppressed in acid as well. This protocol is faster than the phase-solubility method. Moreover, the material requirement is up to four orders of magnitude lower. (c) 2008 Wiley-Liss, Inc. and the American Pharmacists Association
This article was published in J Pharm Sci and referenced in Journal of Chromatography & Separation Techniques

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