Changes in the Physicochemical Properties of Piperine/β-Cyclodextrin due to the Formation of Inclusion Complexes

International Journal of Medicinal Chemistry, Feb 2016

Piperine (PP) is a pungent component in black pepper that possesses useful biological activities; however it is practically insoluble in water. The aim of the current study was to prepare a coground mixture (GM) of PP and β-cyclodextrin (βCD) (molar ratio of PP/βCD = 1/1) and subsequently evaluate the solubility of PP and physicochemical properties of the GM. DSC thermal behavior of the GM showed the absence of melting peak of piperine. PXRD profile of the GM exhibited halo pattern and no characteristic peaks due to PP and βCD were observed. Based on Job’s plot, the PP/βCD complex in solution had a stoichiometric ratio of 1/1. Raman spectrum of the GM revealed scattering peaks assigned for the benzene ring (C=C), the methylene groups (CH2), and ether groups (C-O-C) of PP that were broaden and shifted to lower frequencies. SEM micrographs showed that particles in the GM were agglomerated and had rough surface, unlike pure PP and pure βCD particles. At 15 min of dissolution testing, the amount dissolved of PP in the GM was dramatically increased (about 16 times) compared to that of pure PP. Moreover the interaction between PP and βCD cavity was detected by 1H-1H NMR nuclear Overhauser effect spectroscopy NMR spectroscopy.

A PDF file should load here. If you do not see its contents the file may be temporarily unavailable at the journal website or you do not have a PDF plug-in installed and enabled in your browser.

Alternatively, you can download the file locally and open with any standalone PDF reader:

http://downloads.hindawi.com/journals/ijmc/2016/8723139.pdf

Changes in the Physicochemical Properties of Piperine/β-Cyclodextrin due to the Formation of Inclusion Complexes

Changes in the Physicochemical Properties of Piperine/β-Cyclodextrin due to the Formation of Inclusion Complexes Toshinari Ezawa,1 Yutaka Inoue,1 Sujimon Tunvichien,2 Rina Suzuki,1 and Ikuo Kanamoto1 1Laboratory of Drug Safety Management, Faculty of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado-shi, Saitama 3500295, Japan 2Faculty of Pharmacy, Srinakharinwirot University, Nakhon Nayok 26120, Thailand Received 1 December 2015; Revised 19 January 2016; Accepted 20 January 2016 Academic Editor: Benedetto Natalini Copyright © 2016 Toshinari Ezawa et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Piperine (PP) is a pungent component in black pepper that possesses useful biological activities; however it is practically insoluble in water. The aim of the current study was to prepare a coground mixture (GM) of PP and β-cyclodextrin (βCD) (molar ratio of PP/βCD = 1/1) and subsequently evaluate the solubility of PP and physicochemical properties of the GM. DSC thermal behavior of the GM showed the absence of melting peak of piperine. PXRD profile of the GM exhibited halo pattern and no characteristic peaks due to PP and βCD were observed. Based on Job’s plot, the PP/βCD complex in solution had a stoichiometric ratio of 1/1. Raman spectrum of the GM revealed scattering peaks assigned for the benzene ring (C=C), the methylene groups (CH2), and ether groups (C-O-C) of PP that were broaden and shifted to lower frequencies. SEM micrographs showed that particles in the GM were agglomerated and had rough surface, unlike pure PP and pure βCD particles. At 15 min of dissolution testing, the amount dissolved of PP in the GM was dramatically increased (about 16 times) compared to that of pure PP. Moreover the interaction between PP and βCD cavity was detected by 1H-1H NMR nuclear Overhauser effect spectroscopy NMR spectroscopy. 1. Introduction Piperine [(2E,4E)-1-[5-(1,3-benzodioxol-5yl)-1-oxo-2,4-pentadienyl]piperidine, denoted here as PP] (Figure 1) is a component found in black pepper. PP molecule consists of piperidine and piperic acid linked by an amide bond. PP is pungent; however its cis-trans isomers, that is, isopiperine, chavicine, and isochavicine, have little pungency [1]. PP has been reported for its slight insecticidal activity against third instar larvae of Culex pipiens pallens, Aedes aegypti, and A. togoi [2]. PP at a concentration of 100–500 μg/mL has been reported to exhibit antibacterial action against Staphylococcus aureus, Pseudomonas aeruginosa, Bacillus subtilis, and Escherichia coli [3]. In addition, PP has been reported to reduce thiobarbituric acid reactive substances and the degree of lipid peroxidation [4]. PP activates the sympathetic nerves through the vagus nerve by acting on TRPV1 receptors present at the endings of sensory nerves and the vagus nerve. It is also reported that PP increases the energy consumption of skeletal muscle and brown adipose tissue [5, 6] and facilitates lipolysis in white adipose tissue [7]. Thus, PP has recently drawn attention as a useful spice for use in functional foods. PP is relatively stable in black pepper; however, it is readily isomerized when exposed to ultraviolet light [8]. Therefore, PP in pepper oleoresin must be shielded from light. In addition, because of its low aqueous solubility, PP is unable to exhibit its beneficial actions properly. Figure 1: Chemical structure of (a) piperine (PP), (b) β-cyclodextrin (βCD), and (c) D-glucopyranose. Cyclodextrins (CDs) are cyclic oligosaccharides consisting of D-glucopyranose linked by α-1,4 glycosidic bonds. CDs are classified as α, β, and γCD according to the number of their D-glucopyranose units. CDs have a hydrophilic outer ring and a hydrophobic cavity. CDs are known to form inclusion complexes with various hydrophobic guest molecules by hydrophobic interaction in an aqueous solution [9–11]. Cogrinding is a technique of applying mechanical energy to produce inclusion complexes that is suitable for hydrolysis-prone compounds [12]. The process of encapsulating a guest molecule into the CD cavity has been used in various areas [13]. An inclusion complex of prostaglandin E2/α-CD with increased solubility of prostaglandin E2 has already been utilized in clinical settings. CDs are also widely used as a deodorant and food stabilizer in order to mask undesired properties of active compound [14], to release active compound in a sustained manner [15], and to stabilize active compound [16, 17]. One example is the inclusion complexes between poorly water-soluble capsaicin and β-cyclodextrin (βCD) that led to enhanced solubility and stability of capsaicin [18]. Similarly, formation of curcumin/hydroxypropyl-βCD complexes [19] and alpinetin/hydroxypropyl-βCD complexes [20] has been reported. Also recently, improvem (...truncated)


This is a preview of a remote PDF: http://downloads.hindawi.com/journals/ijmc/2016/8723139.pdf

Toshinari Ezawa, Yutaka Inoue, Sujimon Tunvichien, Rina Suzuki, Ikuo Kanamoto. Changes in the Physicochemical Properties of Piperine/β-Cyclodextrin due to the Formation of Inclusion Complexes, International Journal of Medicinal Chemistry, 2016, 2016, DOI: 10.1155/2016/8723139