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Achievement of pH-independence of poorly-soluble, ionizable loratadine by inclusion complex formation with dimethyl-β-cyclodextrin

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Abstract

A tricyclic, piperidine derivative of antihistamines, loratadine, which belongs in class II of the Biopharmaceutical Classification System, was investigated. It is an ionizable drug, whose solubility depends on the gastrointestinal pH, and the bioavailability is therefore very variable. The aim of this work was to enhance the dissolution and make the solubility of loratadine independent of pH. Inclusion complexes were prepared between loratadine and dimethyl-β-cyclodextrin in two different molar ratios by three techniques (physical mixing, kneading and spray-drying). The formation and physicochemical properties of the inclusion complexes were investigated by means of dissolution tests, thermal analysis and Fourier Transform Infrared spectroscopy. The instrumental examinations proved the presence of partial or total complexes depending on the preparation method and molar ratio, which resulted in better dissolution. For some compositions and preparation methods, the application of this cyclodextrin made the solubility of loratadine independent of pH.

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Acknowledgements

This work was performed with the support of a Sanofi-Aventis Fellowship.

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Authors and Affiliations

  1. Department of Pharmaceutical Technology, University of Szeged, Eötvös u. 6, 6720, Szeged, Hungary

    Á. Nacsa, P. Szabó-Révész & Z. Aigner

  2. Department of Physical Chemistry, University of Szeged, Rerrich B. tér 1, 6720, Szeged, Hungary

    O. Berkesi

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  1. Á. Nacsa
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Correspondence to Z. Aigner.

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Nacsa, Á., Berkesi, O., Szabó-Révész, P. et al. Achievement of pH-independence of poorly-soluble, ionizable loratadine by inclusion complex formation with dimethyl-β-cyclodextrin. J Incl Phenom Macrocycl Chem 64, 249–254 (2009). https://doi.org/10.1007/s10847-009-9558-1

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