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Effect of self-aggregation of γ-cyclodextrin on drug solubilization

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Abstract

The purpose of this study was to investigate the physicochemical properties of drug-saturated aqueous cyclodextrin (CD) solutions. Phase solubility profiles of different drugs were determined in aqueous solutions containing γ-cyclodextrin (γCD) and/or hydroxypropyl-γ-cyclodextrin (HPγCD) in absence or presence of water-soluble polymers. 1H-NMR and turbidity analysis were performed as well as permeation studies. Phase solubility diagrams showed that the observed γCD content (1–20% w/v) was only slightly different from the theoretical values for aqueous solutions that had been saturated with indomethacin, diclofenac sodium or amphotericin B, all displayed A-type profiles, while it was less than the theoretical value in solutions that had been saturated with corticosteroids (hydrocortisone and dexamethasone) that displayed BS-type profiles. In the latter case self-assemble of drug/CD complexes decreased the overall CD solubility. Water-soluble polymers enhanced aqueous solubility of the drugs tested by stabilizing the drug/CD complexes, i.e. enhancing their stability constants, without affecting the observed aqueous γCD solubility. When the drug solubility leveled off (the BS-type profiles) the amount of dissolved γCD increased and approached the theoretical values. Hydrocortisone formed partial inclusion complex with γCD and HPγCD and no non-inclusion or aggregates could be detected in diluted solutions by 1H-NMR. Both permeation and turbidity studies showed that formation of dexamethasone/γCD complex promoted CD aggregation. All these observations indicate that CD aggregate formations play a role in CD solubilization of lipophilic and poorly water-soluble drugs and that the water-soluble polymers enhance the complexation efficiency of γCD and HPγCD by stabilizing the self-assembled drug/CD nanoparticles and promote non-inclusion complex formation.

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Acknowledgements

The financial support provided by the Eimskip fund and the Icelandic Center For Research (RANNÍS) is gratefully acknowledged.

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Authors and Affiliations

  1. Faculty of Pharmaceutical Sciences, University of Iceland, Hofsvallagata 53, 107, Reykjavik, Iceland

    Phatsawee Jansook, Maria D. Moya-Ortega & Thorsteinn Loftsson

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  1. Phatsawee Jansook
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  2. Maria D. Moya-Ortega
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  3. Thorsteinn Loftsson
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Correspondence to Thorsteinn Loftsson.

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Jansook, P., Moya-Ortega, M.D. & Loftsson, T. Effect of self-aggregation of γ-cyclodextrin on drug solubilization. J Incl Phenom Macrocycl Chem 68, 229–236 (2010). https://doi.org/10.1007/s10847-010-9779-3

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  • DOI: https://doi.org/10.1007/s10847-010-9779-3

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