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Characterization of the Dissolution Behavior of Piperine/Cyclodextrins Inclusion Complexes

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Abstract

In this study, the physicochemical properties and solubility of inclusion complexes of ground mixtures (GMs) of piperine (PP), a pungent ingredient of pepper, with α- and γ-cyclodextrin (CD) were studied. From the solubility results, the PP/αCD inclusion molar ratio was determined to be 1/2, while that of PP/γCD was 1/1, according to the AP-type phase diagram of PP/αCD and the BS-type one of PP/γCD. The powder X-ray diffraction and differential scanning calorimetry analyses confirmed the formation of GM complexes with molar ratios of PP/αCD = 1/2 and PP/γCD = 1/1. The Raman analysis revealed the disappearance of the bands corresponding to the C=C, O–CH2–O, −CH, and aliphatic C=C moieties of the methylene dioxyphenyl fragment of PP in the spectra of the inclusion complexes. In the dissolution tests, GM (PP/αCD = 1/2) and GM (PP/γCD = 1/1) showed higher solubility than free PP and the analogous physical mixtures. Furthermore, after 60 min, GM (PP/αCD = 1/2) exhibited higher solubility than GM (PP/γCD = 1/1). In the 1H-1H nuclear Overhauser effect spectroscopy measurements, GM (PP/αCD = 1/2) was found to present a head-to-head inclusion structure via the aliphatic C=C and methylene dioxyphenyl groups of PP and the two αCD molecules. In contrast, it was confirmed that γCD interacts with the O–CH2–O functionality of the methylene dioxyphenyl group of PP in a molar ratio of 1/1. It was thus concluded that the differences in the PP/CD structures influence the solubility of the inclusion complexes.

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Acknowledgements

The authors wish to thank Cyclo Chem Co., Ltd. for providing α-, β-, and γCD and TEK Analysis Inc. for their support with the Raman spectroscopy measurements.

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Authors and Affiliations

  1. Laboratory of Drug Safety Management, Faculty of Pharmacy and Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado-shi, Saitama, 350-0295, Japan

    Toshinari Ezawa, Yutaka Inoue, Isamu Murata & Ikuo Kanamoto

  2. Laboratory of Bioorganic Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado-shi, Saitama, 350-0295, Japan

    Koichi Takao & Yoshiaki Sugita

Authors
  1. Toshinari Ezawa
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  2. Yutaka Inoue
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Correspondence to Yutaka Inoue.

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Ezawa, T., Inoue, Y., Murata, I. et al. Characterization of the Dissolution Behavior of Piperine/Cyclodextrins Inclusion Complexes. AAPS PharmSciTech 19, 923–933 (2018). https://doi.org/10.1208/s12249-017-0908-9

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