European Journal of Pharmaceutical Sciences 2015-02-20

Carrier Mediated Distribution System (CAMDIS): a new approach for the measurement of octanol/water distribution coefficients.

Bjoern Wagner, Holger Fischer, Manfred Kansy, Anna Seelig, Frauke Assmus

文献索引：Eur. J. Pharm. Sci. 68 , 68-77, (2015)

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摘要

Here we present a miniaturized assay, referred to as Carrier-Mediated Distribution System (CAMDIS) for fast and reliable measurement of octanol/water distribution coefficients, log D(oct). By introducing a filter support for octanol, phase separation from water is facilitated and the tendency of emulsion formation (emulsification) at the interface is reduced. A guideline for the best practice of CAMDIS is given, describing a strategy to manage drug adsorption at the filter-supported octanol/buffer interface. We validated the assay on a set of 52 structurally diverse drugs with known shake flask log D(oct) values. Excellent agreement with literature data (r(2) = 0.996, standard error of estimate, SEE = 0.111), high reproducibility (standard deviation, SD < 0.1 log D(oct) units), minimal sample consumption (10 μL of 100 μM DMSO stock solution) and a broad analytical range (log D(oct) range = -0.5 to 4.2) make CAMDIS a valuable tool for the high-throughput assessment of log D(oc)t.Copyright © 2014 Elsevier B.V. All rights reserved.