Characterization of the Dissolution Behavior of Piperine/Cyclodextrins Inclusion Complexes

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 A_P-type phase diagram of PP/αCD and the B_S-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.