Solubility of daidzein in propylene glycol plus water cosolvent mixtures

Highlights

• The solubility of daidzein increases with an increase of propylene glycol composition.

• The Jouyban–Acree model can be used to predict the solubility of daidzein.

• The driving mechanism for the solubility process is discussed.

• Thermodynamic functions are obtained using the van’t Hoff and Gibbs equations.

• Non linear enthalpy–entropy compensation is found.

Abstract

The solubility of daidzein in propylene glycol + water cosolvent mixtures was determined by UV spectrophotometry, and predicted using the Jouyban–Acree model and the mathematical model based on the algebraic rule of mixing. The thermodynamic functions, such as Gibbs energy, enthalpy, and entropy of solution and of mixing and so on, were obtained from these solubility data by using the van’t Hoff and Gibbs equations. The results show that the daidzein solubility increases as propylene glycol proportion increases in the mixtures and the solution temperature increases. The Jouyban–Acree model can be used to predict the solubility of daidzein in propylene glycol + water cosolvent mixtures at different temperatures. The driving mechanism for daidzein solubility in water-rich mixtures is the entropy, probably due to water-structure loss around the drug non-polar moieties by effect of propylene glycol, whereas the driving mechanism is the enthalpy above 0.20 mass fraction of propylene glycol, probably due to daidzein solvation increase by the cosolvent molecules. Non linear enthalpy–entropy compensation with negative slope from water up to 0.20 mass fraction of propylene glycol and positive slope beyond this composition up to pure propylene glycol is found.

Introduction

Daidzein (DZ) (7,4′-dihydroxyisoflavone, Fig. 1) is a major isoflavone found in soybean and other leguminous plant, such as kudzu root. Previous studies have shown that DZ has pharmacological and biochemical effects including antioxidant, anti-inflammatory, cell cycle arrest and estrogen-like biological activities in humans [1], [2], [3], [4], and is widely used as phytoestrogen for menopausal-related disorders, such as cardiovascular disease [5], [6], osteoporosis [7], other menopausal symptoms [8]. Currently, DZ is commercially available as tablets for peroral administration in the China market.

Solubility is an important physicochemical property which plays a basic role in most pharmaceutical and industrial processes. Usually, the low solubility of pharmaceutical compounds causes them to fail during the drug development process, especially of homogeneous liquid pharmaceutical systems. In this way, some water + cosolvent mixtures have been evaluated in order to increase drug solubility and also to permit molecular understanding of solution phenomena and development of homogeneous liquid pharmaceutical products. Propylene glycol (PG), as a hydrogen-donor and hydrogen-acceptor compound, is miscible with water in all proportions, and has been studied in particular as a possible cosolvent in liquid pharmaceutical dosage forms design for several drugs [9]. Moreover, PG has also been used as an evaporation regulator and antimicrobial agent in several liquids formulations [10]. In this study, the solubility of DZ in PG + water cosolvent mixtures at different temperatures was determined.

Experimental solubility determination is a time-consuming and costly process. Several mathematical models have been proposed in the published literature to predict the solubility of drugs in cosolvent + water mixtures [11]. The simplest model to predict drug solubility in cosolvent water mixtures is the one based on the algebraic rule of mixing, which for semipolar compounds in binary mixtures takes the following form:

$$\ln x_m=w_c\ln x_c+w_w\ln x_w$$

where x_m, x_c, x_w, w_c and w_w are the drug solubility calculated in the cosolvent mixture, the drug solubility in the neat cosolvent, the drug solubility in water, the mass fraction of cosolvent in the mixture, and the mass fraction of water in the mixture, respectively. In PG + water cosolvent mixtures, a trained version of the Jouyban–Acree model could be a useful tool for solubility prediction purposes in the pharmaceutical industries [12]. The mathematical model for PG + water cosolvent mixtures at various temperatures is:

$$\ln x_m=f_c\ln x_c+f_w\ln x_w+f_c{f}_w\left[\frac{85.254}{T}+\frac{735.662(f_c-f_w)}{T}\right]$$

where x_m, x_c and x_w are the drug solubility calculated in solvent mixture, PG and water at temperature (T, K), f_c and f_w denote the volume fractions of PG and water in the absence of the solute.

In addition, temperature-solubility dependence allows to perform the respective thermodynamic analysis. So, the objectives of this study are: (1) to measure the solubility of DZ in PG + water cosolvent mixtures at different temperatures; (2) to determine the feasibility of predicting the solubility of DZ in PG + water cosolvent mixtures using two mathematical models; (3) to evaluate the thermodynamic characteristic of DZ dissolved in PG + water cosolvent mixtures based on van’t Hoff method, including the respective contributions by mixing of this compound toward the solution processes.