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Zaleplon co-ground complexes with natural and polymeric β-cyclodextrin

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Abstract

In this study, we compared the suitability of parent β-cyclodextrin (βCD) and its water soluble polymeric derivative (PβCD) as co-grinding additives aimed to enhance the solubility of zaleplon (ZAL), a hypnotic drug. Equimolar drug/carrier mixtures were co-ground in a high-energy micromill over different time intervals. Data obtained by differential scanning calorimetry, X-ray powder diffractometry and scanning electron microscopy showed a higher affinity of ZAL for the solid state interaction with PβCD, resulting in powders with lower relative drug crystallinity (RDC) compared to that obtained with natural βCD (RDC = 51.10 and 12.5 % for complexes with βCD and PβCD co-grounded for 90 min, respectively). On the other hand, grinding the drug alone did not result in a significant reduction of the drug crystallinity (RDC = 99.87 % for the sample ground for 90 min). Although 1H-NMR spectroscopy confirmed that both co-ground products were readily converted into inclusion complexes upon dissolution in water, they presented different dissolution properties. The dissolution velocity of co-ground complex with PβCD was 25 % faster compared to that prepared with the parent βCD and almost double compared to that of the drug alone, irrespective of the pH value of the dissolution media. This clearly demonstrated the suitability of co-ground ZAL/PβCD complex in the development of an immediate release oral formulation of ZAL.

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Acknowledgments

This work was supported by the Grants 006-0061247-1243 and 006-0061117-1244 of the Ministry of Science, Education and Sports of the Republic of Croatia. Financial support by the Access to Research Infrastructures activity in the 7th Framework Programme of the EC (Contract 228461, EAST-NMR) for conducting the NMR research is gratefully acknowledged. Authors are thankful to the Austrian Center for Electron Microscopy and Nanoanalysis Graz, Austria, and Sanja Šimić for their help in conducting the SEM experiments, and to Prof. Paola Mura from the Department of Pharmaceutical Sciences of the University of Florence, Italy, for helping with the sample preparation by high-energy vibrational micro-mills.

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Authors and Affiliations

  1. Department of Analytical Chemistry, Faculty of Pharmacy and Biochemistry, University of Zagreb, A. Kovačića 1, Zagreb, Croatia

    Jasna Jablan & Nikola Kujundžić

  2. Forensic Science Center “Ivan Vučetić”, Ministry of the Interior, Ilica 335, Zagreb, Croatia

    Ivana Bačić

  3. Department of Pharmaceutical Technology, Faculty of Pharmacy and Biochemistry, University of Zagreb, A. Kovačića 1, 10000, Zagreb, Croatia

    Mario Jug

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  1. Jasna Jablan
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Correspondence to Mario Jug.

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Jablan, J., Bačić, I., Kujundžić, N. et al. Zaleplon co-ground complexes with natural and polymeric β-cyclodextrin. J Incl Phenom Macrocycl Chem 76, 353–362 (2013). https://doi.org/10.1007/s10847-012-0206-9

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