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

• Published in: International journal of pharmaceutics 2017-04, Vol.522 (1-2), p.98-109
• Main Authors: Zaman, Hadar, Bright, Andrew G., Adams, Kevin, Goodall, David M., Forbes, Robert T.
• Format: Article
• Language: English
• Subjects: 2-Hydroxypropyl-beta-cyclodextrin; Aggregation; Algorithms; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - chemistry; beta-Cyclodextrins - chemistry; Colchicine - administration & dosage; Colchicine - analogs & derivatives; Colchicine - chemistry; Cyclodextrin; Cyclodextrins - chemistry; Drug Compounding; Excipients; Formulation; Light; Oligopeptides - administration & dosage; Oligopeptides - chemistry; Particle Size; Peptide prodrug; Pharmaceutical Preparations - chemistry; Scattering, Radiation; Solubility; Solubility enhancement; Taylor Dispersion Analysis; Viscosity
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2017.02.012

[Display omitted] 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.