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Controlling the Size, Shape and Stability of Supramolecular Polymers in Water

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Published on: August 2, 2012

Cyclodextrins as solubilizers: formation of complex aggregates.

Phatsawee Jansook¹, Sergey V Kurkov, Thorsteinn Loftsson

¹Faculty of Pharmaceutical Sciences, University of Iceland, Reykjavik, Iceland.

Journal of Pharmaceutical Sciences

|August 12, 2009

Summary

Drug/cyclodextrin complex aggregation increases with cyclodextrin concentration, even with linear phase-solubility diagrams. These findings reveal the formation of complex aggregates in aqueous solutions.

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Area of Science:

Pharmaceutical Sciences
Physical Chemistry

Background:

Drug/cyclodextrin complexation is crucial for drug delivery.
Understanding aggregation behavior is key to optimizing complex stability and efficacy.
Cyclodextrins are widely used to enhance drug solubility and bioavailability.

Purpose of the Study:

To investigate the aggregation of drug/cyclodextrin complexes in aqueous solutions.
To determine the influence of cyclodextrin concentration on complex aggregation.
To correlate aggregation phenomena with phase-solubility diagrams and activity coefficients.

Main Methods:

Drug permeation studies using semi-permeable membranes.
Determination of activity coefficients in drug/cyclodextrin solutions.
Transmission electron microscopy (TEM) for visualizing aggregate formation.

Main Results:

Drug/cyclodextrin complex monomers dominate below 5% (w/v) cyclodextrin concentration.
Aggregate formation increases with cyclodextrin concentration, influencing dissolved complex levels.
TEM confirmed aggregate formation in both pure and drug-saturated cyclodextrin solutions, with diameters ranging from 10-200 nm.

Conclusions:

Aggregation of drug/cyclodextrin complexes occurs progressively with increasing cyclodextrin concentration.
Observed deviations from ideal behavior in activity coefficients indicate concurrent hydration, aggregation, and complexation.
The study highlights the importance of considering aggregation in the formulation of drug/cyclodextrin systems.