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Gamma-cyclodextrin on enhancement of water solubility and store stability of nystatin

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Abstract

The water solubility of nystatin was found enhanced by forming inclusion complex with gamma-cyclodextrin (γ-CD). Further discovery of a pleased surprise showed that the phase solubility curves of nystatin in β- and γ-CD aqueous solution were AL type, while BS type for α-CD, indicating 1:1 inclusion complexes were formed between β-CD, γ-CD and nystatin, but no inclusion complexes for α-CD, in addition, CDs with much larger ring would be more suitable for forming inclusion complexes with macrolide antibiotics. The aqueous solubility of nystatin in γ-CD solution was investigated increased with γ-CD concentration increasing. At the concentration of 24 g/100 ml for γ-CD aqueous solution, which is near to the saturated solution, water solubility of nystatin was found to be 104 μg/ml, which was 103 folds over original nystatin. Inclusion constants for γ-CD–nystatin complexes were 0.539 l/mmol, which is larger than that of β-CD–nystatin complex (0.375 l/mmol). The inclusion complex of γ-CD with nystatin was prepared and detected by infrared spectrum, results showing that the ester linkage and diene were included in the cavity of CDs, while conjugate arachidonic, carboxyl and amino group were left outside of CDs. Storing experiment showed that forming of the inclusion complexes greatly enhanced the stability of nystatin against light and oxygen.

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Acknowledgments

This project was supported by National Natural Science Foundation (Grant No. 31230057). The authors thank financial support by the Fundamental Research Funds for the Central Universities (JUSRP111A30 and JUSRP11122), and by Science and Technology of the Twelfth Five-Year Plan (2012BAD37B02, 2012BAD37B03).

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Correspondence to Zhengyu Jin.

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Wang, J., Jin, Z. & Xu, X. Gamma-cyclodextrin on enhancement of water solubility and store stability of nystatin. J Incl Phenom Macrocycl Chem 78, 145–150 (2014). https://doi.org/10.1007/s10847-012-0281-y

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  • DOI: https://doi.org/10.1007/s10847-012-0281-y

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