Article Cite This: J. Chem. Eng. Data XXXX, XXX, XXX−XXX
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Solubility and Modeling of Hesperidin in Cosolvent Mixtures of Ethanol, Isopropanol, Propylene Glycol, and n‑Propanol + Water Renjie Xu,*,† Yang Cong,‡ Min Zheng,‡ Gaoquan Chen,‡ Jiao Chen,‡ and Hongkun Zhao‡ †
Guangling College, Yangzhou University, YangZhou, Jiangsu 225009, People’s Republic of China College of Chemistry & Chemical Engineering, Yangzhou University, YangZhou, Jiangsu 225002, People’s Republic of China
‡
S Supporting Information *
ABSTRACT: Equilibrium solubility of hesperidin in aqueous solutions of ethanol, isopropanol, propylene glycol, and n-propanol was determined by static technique at temperatures ranging from 293.15 to 333.15 K under p = 101.1 kPa. The hesperidin solubility increased monotonously with the increase in mass fraction of ethanol isopropanol, propylene glycol, and n-propanol and temperature. At the same composition of alcohol and temperature, the mole fraction solubility of hesperidin was largest in propylene glycol + water among the four cosolvent mixtures. The solubilities of hesperidin were correlated with Jouyban−Acree model, Apelblat−Jouyban−Acree model, and van’t Hoff− Jouyban−Acree model. The obtained average relative deviations were less than 2.38%.
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INTRODUCTION Hesperidin is a flavanone glycoside (CAS Registry no. 520-26-3, molecular structure shown in Figure 1) found abundantly in
dosage form, and knowing the mechanism regarding the chemical and physical stability of pharmaceutical solutions. So, it is of great importance to determine the drug solubility in mixed solvents.20−22 Although several semiempirical and theoretical equations may be used to forecast the drug solubility in mixed solvents, the experimental data are needed for pharmaceutical researchers.23 Due to the low solubility of hesperidin in water, the solvent mixtures can be used to improve the drug solubility. It is generally known that ethanol is a safe and common cosolvent employed in the pharmaceutical industry, owing to its high solubilization capacity. Moreover, ethanol may influence the drug’s absorption, metabolism, excretion, and distribution.24 Isopropanol is a colorless and flammable chemical compound with a strong odor. It is miscible with water, ether, ethanol, and chloroform, and it dissolves a wide range of nonpolar solvents. Compared to alternative solvents, it is relatively nontoxic. Isopropanol is employed individually or in mixtures with other solvents for different aims25,26 comprising in penetration-enhancing pharmaceutical compositions for topical transepidermal and percutaneous uses. Propylene glycol is a common cosolvent in pharmacy.27 In contrast, n-propanol is not a common cosolvent in the pharmaceutical industry, however it is usually employed as a solvent for cellulose esters and resins.28 Under the considerations indicated above, the key purpose of the present work is to report the solubility of hesperidin (component 3) in ethanol (1) + water (2), isopropanol (1) + water (2), propylene glycol (1) + water (2), and n-propanol (1) + water (2) mixtures at different temperatures.
Figure 1. Chemical structure of hesperidin.
citrus fruits. It has been widely used in anticancer, antioxidant, antimicrobial, and anti-inflammatory activities.1−6 Nevertheless, its aqueous solubility is very small, which is a key drawback in formulation development,7,8 and it is poorly absorbed in the small intestine, which significantly decreases the drug bioavailability.2,3,9,10 Some toxic or unsafe solvents, e.g., chloroform, methanol, and ether, are often employed in the extraction of bioactive materials.11,12 The above solvents are not appropriate for the formulation progress. Nontoxic/safe solvents, including ethanol, isopropanol, PEG-400, and propylene glycol, have been applied in the formulation process and in the drugs’ solubilization.13−16 Improvement of solubility and bioavailability of hesperidin have been studied by numerous methods, including microparticles, complexation, and nanocrystals.7,17,18 In the previous works, only the solubilities of hesperidin in ethanol, water, isopropanol, 1-butanol, propylene glycol, and PEG-400 are available.19 From practical viewpoints, the drug’s solubility in cosolvent solutions is very essential in the purification of material, design of © XXXX American Chemical Society
Received: November 1, 2017 Accepted: January 26, 2018
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DOI: 10.1021/acs.jced.7b00948 J. Chem. Eng. Data XXXX, XXX, XXX−XXX
Journal of Chemical & Engineering Data
Article
Table 1. Detailed Information of Hesperidin and the Selected Solvents CAS registry number
molar mass g·mol−1
source
hesperidin
520-26-3
610.56
ethanol
64-17-5
46.06
Adamas Reagent Co. Ltd., China Sinopharm Chemical Reagent Co., Ltd., China
isopropanol propylene glycol n-propanol water
67-63-0 57-55-6
60.10 76.09
71-23-8 7732-18-5
60.10 18.01
chemicals
a
initial mass fraction purity
final mass fraction purity
purification method
HPLCa
0.981
0.997
0.995
0.995
GCb
0.994 0.994
0.994 0.994
GC GC
0.995
0.995 conductivity
