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

Toshinari Ezawa; Yukiko Inagaki; Kinami Kashiwaba; Namiko Matsumoto; Hajime Moteki; Isamu Murata; Yutaka Inoue; Mitsutoshi Kimura; Masahiko Ogihara; Ikuo Kanamoto

doi:10.1021/acsomega.0c06198

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

ACS Omega. 2021 Mar 3;6(10):6953-6964. doi: 10.1021/acsomega.0c06198. eCollection 2021 Mar 16.

Affiliations

¹ Laboratory of Drug Safety Management, Faculty of Pharmacy and Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama 3500295, Japan.
² Laboratory of Clinical Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama 3500295, Japan.

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 ¹H-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.