Solubility of Thiamine in Pure and Mixed Solvents in Function of Temperature

Vitamin B1 (C12H67ClN4OS.HCl, molecular weight = 337.33 g mol–1), also called thiamine, has great importance in the food industry in general. Thiamine is a vitamin belonging to the B complex, and can be found in the cuticle of rice, brewer’s yeast, grains, egg yolk, liver, kidney, pork, fish, peanut, walnut, legumes, as well asin green and leafy vegetables. It acts in different parts of the body and plays a major role in the nervous, muscular and cardiovascular systems, in addition to assisting in glucose metabolism. Thiamine deficiency causes brain damage and in some cases it may be irreversible. Among the diseases caused by vitamin B1 deficiencies are: Beriberi, Wernicke’s encephalopathy and Korsakoff’s syndrome1. Thiamine is not stored in large amounts in the body, with provision from the daily diet being necessary. Thiamine is unstable in alkali conditions and is heat stable at acidic pH values. Thiamine solubility data in water are widely found in the literature. However, solubility data in alternative solvents such as dimethylsulfoxide (DMSO) and DMSO + water mixtures may be important for studies of separation and purification of the feedstock. On the other hand, the crystallization processes of thiamine require a large amount of accurate solubility data. Unfortunately, there is a lack of solubility data that indicates the solubility dependence as a function of temperature and of the initial solvent mixture composition2,4. Thus, obtaining solubility data for thiamine under known conditions of temperature, pressure and concentration of the initial mixture of solvents is important in order to improve manufacturing processes and purification (crystallization) of this vitamin.


Introduction
Vitamin B1 (C 12 H 67 ClN 4 OS.HCl, molecular weight = 337.33g mol -1 ), also called thiamine, has great importance in the food industry in general.Thiamine is a vitamin belonging to the B complex, and can be found in the cuticle of rice, brewer's yeast, grains, egg yolk, liver, kidney, pork, fish, peanut, walnut, legumes, as well asin green and leafy vegetables.It acts in different parts of the body and plays a major role in the nervous, muscular and cardiovascular systems, in addition to assisting in glucose metabolism.Thiamine deficiency causes brain damage and in some cases it may be irreversible.Among the diseases caused by vitamin B1 deficiencies are: Beriberi, Wernicke's encephalopathy and Korsakoff's syndrome 1 .Thiamine is not stored in large amounts in the body, with provision from the daily diet being necessary.Thiamine is unstable in alkali conditions and is heat stable at acidic pH values.
Thiamine solubility data in water are widely found in the literature.However, solubility data in alternative solvents such as dimethylsulfoxide (DMSO) and DMSO + water mixtures may be important for studies of separation and purification of the feedstock.On the other hand, the crystallization processes of thiamine require a large amount of accurate solubility data.Unfortunately, there is a lack of solubility data that indicates the solubility dependence as a function of temperature and of the initial solvent mixture composition 2,4 .Thus, obtaining solubility data for thiamine under known conditions of temperature, pressure and concentration of the initial mixture of solvents is important in order to improve manufacturing processes and purification (crystallization) of this vitamin.

Materials
Vitamin B1 with a mass fraction >99.0 % was obtained from Synth ® .The organic solvent, DMSO was obtained from Vetec ® with 99.9 % purity.All chemicals were used without further purification.

Apparatus and procedure
In the assays, solubility data of thiamine electrolyte were determined in mixed solvents as a function of temperature by the static method followed by a gravimetric analysis [3][4][5][6] .The experimental work was performed at atmospheric pressure in the temperature range from 298.15 K to 313.15 K.In this article, the experimental apparatus for measuring the solubility of the vitamin B1 was a jacketed glass cell (volume = 35.0•10 - m³).The temperature was regulated by a thermostatic bath and the cell temperature was measured by a thermometer with uncertainty ± 0.1 K. Saturated solutions of the vitamin were prepared with different concentrations in DMSO and double-distilled and deionized water.The solutions Solubility of Thiamine in Pure and Mixed Solvents in Function of Temperature were prepared to achieve equilibrium with electrolyte excess, while they were subjected to a constant temperature.A magnetic stirrer was used to promote the agitation of the solution and ensure the establishment of equilibrium.The stirring period consisted of 162 minutes, followed by a rest period of 180 minutes.Different stirring periods were tested to determine a suitable equilibrium time.It was found that 162 minutes after stirring had stopped was enough time for thiamine in solvent to reach equilibrium, because repetitive measurements during the following several hours indicated the results are reproducible.Finally, the sampling was made in triplicate.The samples were withdrawn from a previously thermostatized syringe according to the temperature of the solution.The sample analysis was made from the gravimetric method.In Figure 1, the layout of the experimental apparatus is presented.

Solubility data
The data of thiamine mole fraction solubility in mixed solvents as a function of temperature are listed in Table 1 and Figure 2. All experimental data are included in Table 1.In this table, m is the thiamine molality with the experimental standard deviation among three samples.By analyzing the data for each temperature, it can be noted that all of them have a maximum point at the maximum water concentration.This occurs because thiamine is a water-soluble vitamin 7 .From Table 1 and Figure 2, we can conclude that the thiamine solubility in all the mixed solvents increases with the increase in both temperature and mass fraction of water in DMSO solution.
The results suggest that an explanation for the increased solubility of thiamine with increasing mass fraction of water is based on the fact that thiamine is a molecule with a highly polar structure.Thus, the smaller and less voluminous water molecule clusters more easily around the thiamine molecules than the bulkier DMSO.

Data correlation
The relationship between the solubility measured by the molality and the temperature was proposed by mathematical models available in the literature [8][9][10] represented by Equations 1, 2 and 3, respectively.(2006).Thus, the superscripts h, y and r were used to differentiate the parameters obtained in the fits.In this article, Heidman, Yaws and Rasmuson models have been changed in order to obtain better results.These modified models are represented by Equations 4, 5, and 6, respectively, similar to the literature 6 .ln ln The experimental points were fitted by non-linear regression using the Levenberg-Marquardt method 11 to obtain the dimensionless parameters and r C to solve the optimization problem.The objective function was used to minimize the sum of squared residuals.In three fittings, the parameters presented low standard deviations.The parameters calculated for these models have shown low standard deviation.The accuracy of the adjustments was also verified by the observed quadratic correlation coefficients (R²).All correlation coefficients were >97 %, indicating that the calculated parameters with more than 97 % of the variability in the data could be explained by the rational models employed.In all settings, the averages of relative deviations between the values obtained by the model and the values obtained in the laboratory were calculated.The average to relative deviations, s h , s y and s r were calculated by the following equations: Where m is the experimental data and NP is the number of experimental points.
The values obtained for the modified models of Heidman, Yaws and Rasmuson identified by H, Y and R, respectively, are shown in Table 2.The average for the relative deviations of the fitted data for the system thiamine + water + DMSO were 0.054 %, 4.261 % and 0.279 % for Heidman, Yaws and Rasmuson fittings, respectively.The experimental standard deviations for the thiamine solubility data in mixtures of solvents (DMSO + water) are shown in Figures 3, 4 and 5, respectively.According to Figures 3, 4 and 5, it is possible to observe that the fitting of the three models displayed no biased characteristics.In all cases, the average of relative deviations calculated was lower than 4.3 %.This fact indicates that the models have adjusted well to the experimental data.One can also say that the three equations presented are able to predict with good accuracy the solubility values for the systems studied in the cited conditions.
It is noted in this case that the average of relative deviations was smaller than 4.3 %, which shows little variation between the results correlated by the models and those obtained experimentally.On the other hand, the correlation coefficients for the three models showed values higher than 97.8 %.Given the above, it can be seen that these models are also suitable for the correlation/prediction of the experimental data obtained in the laboratory under specified conditions.

Conclusion
The thiamine solubility data in the solvent mixture (water + DMSO) demonstrates, in an isothermal system, that the solubility of the vitamin is very high in water (highly hygroscopic solution); it increased before increasing the concentration of water as a cosolvent in combination with DMSO.This is common behavior among vitamins as observed in the literature 7 .Additionally, it is observed that thiamine solubility also increases with increasing temperature, as observed in the literature 7,[12][13][14] .An adequate relationship between the experimental results and the results described by the fitting models was observed.Finally, it was observed that the models satisfactorily accounted for the variability of experimental data obtained.

F i g . 3 -
Experimental standard deviations for the data of solubility of thiamine in mixtures of solvents (DMSO + water) for adjustments Heidman