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

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    Publication date
    2017-04-30
    Author
    Zaman, Hadar
    Bright, A.G.
    Adams, Kevin
    Goodall, D.M.
    Forbes, Robert T.
    Keyword
    Taylor dispersion analysis; Peptide prodrug; Aggregation; Cyclodextrin; Solubility enhancement formulation
    Rights
    (c) 2017 Elsevier. Reproduced in accordance with the publisher's self-archiving policy. This manuscript version is made available under the CC-BY-NC-ND 4.0 license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
    Peer-Reviewed
    Yes
    
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    Abstract
    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-β-cyclodextrin. 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-β-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.
    URI
    http://hdl.handle.net/10454/14020
    Version
    Accepted manuscript
    Citation
    Zaman H, Bright AG, Adams K et al (2017) Characterisation of aggregates of cyclodextrin-drug complexes using Taylor Dispersion Analysis. International Journal of Pharmaceutics. 522(1-2): 98-109.
    Link to publisher’s version
    https://doi.org/10.1016/j.ijpharm.2017.02.012
    Type
    Article
    Collections
    Life Sciences Publications

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