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Solid-state characterization and dissolution properties of ezetimibe–cyclodextrins inclusion complexes

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Abstract

The objectives of this research were to prepare and characterize inclusion complex of Ezetimibe (EZE) with cyclodextrins (β-cyclodextrin (β-CD) and hydroxypropyl-β-cyclodextrin (HPβ-CD)) and to study the effect of complexation on the dissolution rate of EZE, a water insoluble drug. Phase solubility curve was classified as A P -type for both cyclodextrins, indicating the 2:1 stoichiometric ratio for β-CD–EZE and HPβ-CD – EZE inclusion complexes. The inclusion complexes in the molar ratio of 2:1 (β-CD–EZE and HPβ-CD–EZE) were prepared by various methods such as kneading, coevaporation and physical mixing. The molecular behaviors of drug in all samples were characterized by fourier-transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD) studies. The results of these studies indicated that complex prepared by kneading and coevaporation methods showed inclusion of the EZE molecule into the cyclodextrins cavities. The highest improvement in in-vitro dissolution profiles was observed in complex prepared with hydroxypropyl-β-cyclodextrin using co-evaporation method. Mean dissolution time and similarity factor indicated significant difference between the release profiles of EZE from complexes and physical mixtures and from pure EZE.

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Acknowledgements

We would like to thank Zydus Cadila, India for donating EZE and conducting PXRD studies of the samples. We are grateful to Maan Pharmaceuticals Ltd. for providing formulation excipients.

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  1. Department of Pharmaceutics, S.K. Patel College of Pharmaceutical Education and Research, Ganpat University, Kherva, Mehsana-Gozaria Highway, Ganpat vidyanagar, 390 001, Gujarat, India

    R. Patel, D. Bhimani, J. Patel & D. Patel

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  1. R. Patel
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  2. D. Bhimani
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Correspondence to R. Patel.

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Patel, R., Bhimani, D., Patel, J. et al. Solid-state characterization and dissolution properties of ezetimibe–cyclodextrins inclusion complexes. J Incl Phenom Macrocycl Chem 60, 241–251 (2008). https://doi.org/10.1007/s10847-007-9371-7

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