Determination of binding constants of cyclodextrin inclusion complexes with amino acids and dipeptides by potentiometric titration

Kahle, Claudia; Holzgrabe, Ulrike

doi:10.1002/chir.20068

Cited by 65 publications

(41 citation statements)

References 31 publications

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“…This approach gives f b = 0.96 and suggests that the colchicine would be present mostly bound to cyclodextrin. Whilst no data are available for HP--CD solubilisation or binding for other groups in ICT01-2588, binding constants, K, with -CD have been documented for fluorescein, 360 M -1 (Flamigni, 1993), tyrosine, 48 M -1 (Bekos et al, 1996), phenylalanine, 85 M -1 (Kahle and Holzgrabe, 2004) (no value available for homophenylalanine). Assuming K values for HP--CD are similar to those for -CD, and comparability between groups either free or part of the ICT01-2588 sequence, estimates of the fractions bound can be made using Eq.…”

Section: Ict01-2588 Binding To Hp--cdmentioning

confidence: 99%

Characterisation of aggregates of cyclodextrin-drug complexes using Taylor Dispersion Analysis

Zaman

Bright

Adams

et al. 2017

International Journal of Pharmaceutics

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There is a need to understand the nature of aggregation of cyclodextrins (CDs) with guest molecules in increasingly complex formulation systems. To this end an innovative application of Taylor dispersion analysis (TDA) and comparison with dynamic light scattering (DLS) have been carried out to probe the nature of ICT01-2588 (ICT-2588), a novel tumor-targeted vascular disrupting agent, in solvents including a potential buffered formulation containing 10% hydroxypropyl-betacyclodextrin. The two hydrodynamic sizing techniques give measurement responses are that fundamentally different for aggregated solutions containing the target molecule, and the benefits of using TDA in conjunction with DLS are that systems are characterised through measurement of both mass-and z-average hydrodynamic radii. Whereas DLS measurements primarily resolve the large aggregates of ICT01-2588 in its formulation medium, methodology for TDA is described to determine the size and notably to quantify the proportion of monomers in the presence of large aggregates, and at the same time measure the formulation viscosity. Interestingly TDA and DLS have also distinguished between aggregate profiles formed using HP-beta-CD samples from different suppliers. The approach is expected to be widely applicable to this important class of drug formulations where drug solubility is enhanced by cyclodextrin and other excipients. To: The Editor, International Journal of Pharmaceutics From: Rob Forbes and David GoodallWe have revised the manuscript to reflect the amendments of the reviewers. The original cover letter is below.We are submitting this article, which describes novel work showing benefits of use of Taylor dispersion analysis in conjunction with dynamic light scattering to characterize ICT01-2588, a tumour-targeted vascular disrupting agent, in a potential formulation medium containing 10% hydroxypropyl--cyclodextrin as a solubility enhancing agent. Our approach is expected to be widely applicable to this important class of drug formulations where drug solubility is enhanced by cyclodextrin and other excipients, and is a contribution to advancing an understanding of the nature of self-assembly in such complex systems.The lead reviwer suggested is Thorsteinn Loftsson, who is a member of your Editorial Advisory Board. We cite a number of his papers. Of the other suggested referees. We cite work on Taylor dispersion analysis by the other two proposed referees, Ana Ribeiro and Jesper Ostergaard, and Robert HoylstPlease note that if possible we would like to name two corresponding authors, Robert T. Forbes (lead corresponding author) and David M. Goodall (second corresponding author). If this is not possible, it should be just Robert T. Forbes. The bulk of this work was conducted whilst Professor Forbes was at the University of Bradford, which is listed as his affiliation #1. He is currently at the University of Central Lancashire, which is listed as affiliation #2.Regarding declaration of conflict of interest guidelines, please note the foll...

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Section: Ict01-2588 Binding To Hp--cdmentioning

confidence: 99%

Characterisation of aggregates of cyclodextrin-drug complexes using Taylor Dispersion Analysis

Zaman

Bright

Adams

et al. 2017

International Journal of Pharmaceutics

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“…in which α corresponds to the negative logarithm of the activity coefficient of H 3 O + at the working temperature and ionic strength; S stands for the Nernst slope; the j H term corrects pH readings for the nonlinear pH response due to liquid junctions and asymmetry potentials in acidic solutions (pH 1.5-2.5): the j OH term corrects for non-linear effects at high pH (pH > 11) [17], and K w stands for the aqueous constant as a function of ionic strength and temperature [18]. Four-Plus terms α, S, j H , j OH are characteristic of the electrode performance.…”

Section: Apparatusmentioning

confidence: 99%

Determination of Acid Dissociation Constants of Poorly Water-Soluble Nicotinic Ligands by Means of Electrophoretic and Potentiometric Techniques

Roda¹,

Dallanoce²,

Gambaro³

et al. 2015

Pharm Anal Acta

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Objectives: Acid-base dissociations constants of a series of poorly water-soluble nicotinic ligands designed as anti-inflammatory agents were determined in order to characterize the pharmacokinetic profile of this kind of ligands.Methods: pK a s values were assessed by means of potentiometric and electrophoretic methods and investigated by computational protocols.Results: Both electrophoretic and potentiometric measurements produced reliable results. However, with the electrophoretic technique only an average value for close pK a s was found, whereas the potentiometric method allowed determination of each pK a value in water-cosolvent mixtures. A theoretical treatment with various prediction programs -i.e. ADME Boxes v. 4.1, ACD/pK a DB and ACD/pK a GALAS -led in most cases to values which were not in accordance with the experimental ones. Conclusion:Electrophoretic and potentiometric techniques showed complementary features. Indeed, with capillary electrophoresis, the problem associated with the low water solubility of the studied samples could be easily overcome, although this technique did not allow to measuring all dissociation constants. In contrast, application of the potentiometric method afforded all the theoretical pK a values, although we had to perform the titrations in watercosolvent mixtures, a less precise, more laborious and time-consuming approach.

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“…18,19 Base titrant (0.5 M KOH) was prepared from CO2-free ampoules of KOH in order to minimize the concentration of CO2 in the solution. This reagent was standardized by titration with a weighed amount (0.15 to 0.19 g) of KHP dissolved in 20 ml of ISA water.…”

Section: Apparatusmentioning

confidence: 99%

Determination of Acid Dissociation Constants of Compounds Active at Neuronal Nicotinic Acetylcholine Receptors by Means of Electrophoretic and Potentiometric Techniques

et al. 2010

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Determination of binding constants of cyclodextrin inclusion complexes with amino acids and dipeptides by potentiometric titration

Cited by 65 publications

References 31 publications

Characterisation of aggregates of cyclodextrin-drug complexes using Taylor Dispersion Analysis

Characterisation of aggregates of cyclodextrin-drug complexes using Taylor Dispersion Analysis

Determination of Acid Dissociation Constants of Poorly Water-Soluble Nicotinic Ligands by Means of Electrophoretic and Potentiometric Techniques

Determination of Acid Dissociation Constants of Compounds Active at Neuronal Nicotinic Acetylcholine Receptors by Means of Electrophoretic and Potentiometric Techniques

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