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Rapamycin-cyclodextrin complexation: improved solubility and dissolution rate

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Abstract

The objective of this study was to improve poor aqueous solubility and dissolution properties of anticancer drug rapamycin through formation of inclusion complexes with natural and modified cyclodextrins. Of the cyclodextrins tested, γ-cyclodextrin and hydroxypropyl-γ-cyclodextrin did not complex with rapamycin. However, complexes of rapamycin with β-cyclodextrin, methyl-β-cyclodextrin and hydroxypropyl-β-cyclodextrin were prepared and characterized by techniques such as Fourier Transform infrared spectroscopy, differential scanning calorimetry, phase solubility analysis and in vitro dissolution studies. According to the characterization data for the complexes, rapamycin water solubility was highly enhanced by all three β-cyclodextrins with methyl-β-cyclodextrin complex resulting in particularly higher solubility enhancement. FTIR spectra and DSC thermograms supported the formation of inclusion complexes. The complexes showed highly improved dissolution rate in water. Complexation with cyclodextrin derivatives such as methyl-β-cyclodextrin and hydroxypropyl-β-cyclodextrin can provide promising alternatives for the formulation of rapamycin.

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Abbreviations

CD:

Cyclodextrin

βCD:

β-Cyclodextrin

MβCD:

Methyl-β-cyclodextrin

HPβCD:

Hydroxypropyl-β-cyclodextrin

γCD:

γ-Cyclodextrin

HPγCD:

Hydroxypropyl-γ-cyclodextrin

Rapa:

Rapamycin

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Acknowledgments

Authors wish to thank Dr. Christoph Winterhalter-Wacker Chemie AG, Germany for the kind supply of CAVASOL® products used in this study. Prof. Murat Şen from Department of Polymer Chemistry, Chemistry Division, Hacettepe University-Ankara is acknowledged for his assistance in FTIR and DSC analysis. Mr. Erhan Vargun of Varpa Co. Ltd, Ankara is also acknowledged for his support during the study.

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Authors and Affiliations

  1. Faculty of Pharmacy, Yeditepe University, Inonu Mah. 26 Agustos Yerlesimi, Kayisdagi Caddesi, 34755, Atasehir, Istanbul, Turkey

    M. Abdur Rouf & Dilek Demir Erol

  2. Department of Pharmaceutical Technology, Faculty of Pharmacy, Hacettepe University, 06100, Sihhiye, Ankara, Turkey

    Imran Vural, Erem Bilensoy & Atilla Hincal

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  1. M. Abdur Rouf
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  2. Imran Vural
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  3. Erem Bilensoy
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Correspondence to M. Abdur Rouf.

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Abdur Rouf, M., Vural, I., Bilensoy, E. et al. Rapamycin-cyclodextrin complexation: improved solubility and dissolution rate. J Incl Phenom Macrocycl Chem 70, 167–175 (2011). https://doi.org/10.1007/s10847-010-9885-2

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  • DOI: https://doi.org/10.1007/s10847-010-9885-2

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