Solubility of Piperine and Its Inclusion Complexes in Biorelevant Media and Their Effect on Attenuating Mouse Ileum Contractions

Abstract

This study evaluated the solubility of piperine (PP) in biorelevant media and the effect of its ground mixtures (GMs) and coprecipitates (CPs) on intestinal contractions when presented in inclusion complexes with α-, β-, and γ-cyclodextrins (CDs). In the powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC) measurements, CP (PP/αCD) and CP (PP/γCD) suggest the formation of inclusion complexes. The 1 H-nuclear magnetic resonance (NMR) analysis showed the integrated intensity ratios of CP (PP/αCD) and CP (PP/γCD) protons to be 1/2 and 1/1, the same as the respective molar ratios in the respective GM inclusion complexes. The intestinal contraction test confirmed that the intestinal contraction rate of carbachol (CCh) in the presence of 2.0 × 10 –5 M PP was comparable to that in the absence of PP. On the other hand, CP (PP/αCD), GM (PP/αCD = 1/2), and GM (PP/βCD = 1/1) formed inclusion complexes that significantly suppressed the intestinal contractility at PP 1.0 × 10 –8 M. No significant differences were observed between CP and GM. The solubility of the PP/αCD inclusion complex was 6–7 times higher than that of PP in the fasted-state-simulated intestinal fluid (FaSSIF, pH 6.5). PP functioned to suppress intestinal contraction by forming an inclusion complex. Based on this result, PP/αCD might be expected to be effective as an antidiarrheal.

Structural Studies of Piperine Inclusion Complexes in Native and Derivative β-Cyclodextrins

“…The inclusion of piperine in native β -CD has been studied by various spectroscopic (phase solubility studies, Job’s Plot, FT-IR, near-infrared spectroscopy (NIR), Raman, 1 H-NMR, UV-visible absorption and fluorescence intensity study, powder X-ray diffraction (PXRD)) and calorimetric (differential scanning calorimetry (DSC) and thermogravimetry (TG)) methods as well as by scanning electron microscopy (SEM) [ 18 , 19 , 20 , 21 , 22 , 23 ]. The above methods indicated the formation of PN/ β -CD complexes of either 1:1 or 1:2 guest:host stoichiometry, according to the interactions found between the aromatic ring of PN and β -CD, with complexation efficiency varying from 7 to 70% for various stoichiometric ratios.…”