Article pubs.acs.org/jced
Cite This: J. Chem. Eng. Data XXXX, XXX, XXX−XXX
Solubility of Bifonazole in Four Binary Solvent Mixtures: Experimental Measurement and Thermodynamic Modeling Jianqiang Zhang,† Chunjuan Huang,‡ and Renjie Xu*,‡ †
Henan Provincial Key Laboratory of Surface & Interface Science, Zhengzhou University of Light Industry, Henan 450001, People’s Republic of China ‡ Guangling College, Yangzhou University, Yangzhou, Jiangsu 225000, People’s Republic of China
Downloaded via UNIV OF ROCHESTER on May 13, 2019 at 22:50:05 (UTC). See https://pubs.acs.org/sharingguidelines for options on how to legitimately share published articles.
S Supporting Information *
ABSTRACT: Methanol (n-propanol, isopropanol, and propylene glycol) and water were mixed in different proportions to form four mixed solvents, which were applied to dissolve bifonazole. The mole fraction of bifonazole was determined by the isothermal dissolution equilibrium technique within T = 278.15−318.15 K and P = 101.1 kPa under the condition that the dissolution system reached equilibrium. The increase in the ratio of organic solvent to water in the mixed solvents and temperature promoted the increase in the solubility of bifonazole. The solvent formed by mixing methanol and water in different proportions was most beneficial for the dissolution of bifonazole in all solution systems at the same percentage of organic solvent and the same temperature. Moreover, the calculated results of the Jouyban−Acree model, the van’t Hoff− Jouyban−Acree model and the modified Apelblat−Jouyban−Acree model are in good agreement with the solubility data of the experimentally measured bifonazole. The mole fraction calculated by the model is not completely consistent with the experimental result, and the maximum average relative deviation between them is 2.76%. The determination of the solubility data of the drug in the mixed solvent is of great value for the improvement of the physical and chemical information of the drug and the analysis of the thermodynamic properties.
■
INTRODUCTION Bifonazole (CAS registry no. 60628-96-8, chemical structure shown in Figure S1 of the Supporting Information) is also called 1-[phenyl-(4-phenylphenyl)methyl]imidazole, which is a novel imidazole topical antifungal drug. In the last few years, some systemic fungal infections have caused serious threats to human life and bifonazole is often given priority in the treatment of diseases caused by fungal infections, for example, tinea manuum, tinea pedis, and tinea cruris, which were caused by mold.1,2 Not only that bifonazole is also very helpful for the control of cancer cells, but it can be used in combination with antibiotics such as penicillin to treat lung cancer, rectal cancer, and prostate cancer.3 What is more, bifonazole also can be selected as a carrier for low water solubility drugs. The slow release of the drug in the carrier has a surprising effect on the treatment of intravesical infection and cystitis glandularis.4 In addition, bifonazole has an inhibitory effect on parasites and is therefore capable of treating parasite-mediated inflammations (demodicosis, stomatitis, dermatophytosis, etc.).5 Even more surprising is that bifonazole is also applied to form a compound drug with herbal extracts to protect the liver.6 Moreover, Due to the excellent chemical properties of bifonazole, it can be employed as a raw material for a membrane gel composition to protect damaged skin from infection.7 At the same time, it also has an irreplaceable role in helping leuconychia to return to normal form.8 In the current production process of bifonazole, mostly imidazole is used as the raw material for production, so it is inevitable to mix a certain amount of imidazole in the crude product.9,10 Therefore, in the © XXXX American Chemical Society
next step, purification of the bifonazole crude product is an essential link. Thus, understanding the solubility properties of bifonazole is essential to provide the most basic theoretical data for subsequent purification processes. Furthermore, although bifonazole has been used as a drug for a long time, it is unfortunate that its data on solid−liquid equilibrium in some common organic solvents has hardly been reported in previous reports. For the fine chemical industry, the separation and purification of crude products is a very important section and understanding the solubility properties of pharmaceuticals is the primary prerequisite for designing refined sections, because these contribute to the purification of the drug substance, the design of the drug formulation, and further understanding of the dissolution mechanism of the drug. Because of this, systematically determining the solubility of drugs in pure solvents and binary mixed solvents is an indispensable link.11−13 Although the addition of an organic solvent to water to increase the dissolution of solutes is not a new method, it is convenient to explore the mechanism of solubilization or solubilization of solutes in pure solvents and the preferential solvation effect mechanism of solutes in mixed solvents by this means.14,15 In the field of thermodynamics, the data measured by experiments alone is not scientific, it is necessary to verify the Received: January 29, 2019 Accepted: May 3, 2019
A
DOI: 10.1021/acs.jced.9b00097 J. Chem. Eng. Data XXXX, XXX, XXX−XXX
Journal of Chemical & Engineering Data
distillation
recrystallization
0.997 0.995 0.995 0.995 0.995 conductivity
