CHAPTER 7 RESULTS AND DISCUSSIONshodhganga.inflibnet.ac.in/bitstream/10603/15244/12/12...Hydrotropes...

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CHAPTER 7

RESULTS AND DISCUSSION

7.1 INTRODUCTION

This chapter discusses the results of the experimental investigations

carried out and are presented in seven sections. Section one and two discuss

the effect of hydrotropes on the solubility and mass transfer coefficient of

acids and alizarin respectively. Section three discusses the effectiveness of

hydrotropes based on Setschenow constant (Ks) values of each hydrotrope

towards a series of acids and alizarin studied. Section four discusses about

association constants (K2 and Khs) from association model which is used to

represent the solubilization of organic acids and alizarin in hydrotrope

solutions.

Section five discusses the influence of solution properties on the

possible mechanism for the solubilizing effect of hydrotropes. Section six

presents the results obtained using artificial neural network model. The

predicted results were compared with experimental values and statistically

discussed. Section seven discusses the extraction of mangiferin from

mango leaves using hydrotrope solutions. In this section the experimental data

obtained were statistically analyzed using Response Surface Methodology

(RSM) and the extraction condition for maximum yield of mangiferin was

discussed.

51

The permutations and combinations of various acid-hydrotrope and

alizarin-hydrotrope systems studied with different hydrotropes under a wide

range of hydrotrope concentrations at different temperatures come to about

2180 experimental data.

7.2 EFFECT OF HYDROTROPES ON THE SOLUBILITY OF

ORGANIC ACIDS AND ALIZARIN

7.2.1 Hydortopes

Hydrotropes such as sodium salicylate, sodium benzoate,

nicotinamide, urea and potassium p-toluene sulfonate (KPTS) were used to

study the effect on solubility of organic acids and alizarin. For organic acids

such as benzoic acid, p-hydroxybenzoic acid, p-nitrobenzoic acid and

cinnamic acid, the two hydrotropes namely sodium salicylate (used for

antiseptic preparations) and sodium benzoate (used as a preservative in food

industry) from aromatic carboxylate group were used in the solubilization

studies.

The other hydrotropes, nicotinamide and urea were selected for

comparison. Since the organic compound alizarin has phenyl group, the

hydrotrope, potassium p-toluene sulfonate with aromatic ring structure is

specifically used for its solubilization study. These hydrotropes are

conventionally used in detergent formulations and drug solubilizations.

Hydrotropes selected for this study are freely soluble in water, non toxic and

does not produce any temperature effect when dissolved in water.

7.2.1.1 Effect of sodium salicylate on benzoic acid

Experimental data on the effect of hydrotrope, sodium salicylate, on

the solubility of benzoic acid is plotted in Figure 7.1. In each case, the

52

influence of a wide range of hydrotrope concentration as well as different

system temperatures on the solubility of benzoic acid is also presented.

The solubility of benzoic acid in water at 303K in the absence of the

hydrotrope, sodium salicylate has been observed to be 3.21 x 10-2

mol/L

(Table 7.1). When sodium salicylate was dissolved as the hydrotrope in the

aqueous phase, no appreciable increase in the solubility of benzoic acid from

the value 3.21 x 10-2

mol/L has been observed until 0.50 mol/L of sodium

salicylate was added in the aqueous phase. Above 0.50mol/L, the solubility of

benzoic acid was increased significantly. On further increase in sodium

salicylate concentrations up to 2.50mol/L in the aqueous phase, a clear

increasing trend in the solubility of the benzoic acid was observed and this

trend was maintained up to the solubility value of 30.28 x 10-2

mol/L of

benzoic acid. Beyond 2.50 mol/L of sodium salicylate, no appreciable

increase in the solubility of benzoic acid was observed.

It was observed that the hydrotrope solution containing sodium

salicylate increases the solubility of benzoic acid significantly only above a

concentration of 0.50 mol/L of sodium salicylate. Below this concentration,

no appreciable increase in the solubility of acids takes place. This

concentration of hydrotrope (sodium salicylate) i.e. 0.50 mol/L required to be

present in the aqueous phase to initiate significant solubilization of benzoic

acid is termed as Minimum Hydrotrope Concentration (MHC).

From Figure 7.1 it can be observed that, above 2.50 mol/L of

sodium salicylate concentration, no appreciable increase in the solubility of

benzoic acid was seen even up to the concentration of 3.00mol/L. This

concentration of sodium salicylate in the aqueous phase i.e. 2.50mol/L

beyond which no further increase in the solubility of benzoic acid takes place

is termed as Maximum Hydrotrope Concentration (Cmax).

53

Table 7.1 Effect of sodium salicylate concentration (C) on the

solubility (S) of benzoic acid in water

S.NoC,

mol/L

102 S, mol/L

T = 303K T = 313K T = 323K T = 333K

1 0.00 3.21 4.04 5.13 6.08

2 0.10 3.23 4.08 5.36 6.93

3 0.20 3.32 4.13 5.73 7.21

4 0.30 3.36 4.37 5.94 7.39

5 0.40 3.43 4.39 6.03 7.53

6 0.50*

5.29 7.58 10.09 12.01

7 0.60 6.43 8.79 12.04 18.7

8 0.70 7.81 12.76 14.63 22.94

9 0.80 9.32 14.34 19.31 31.73

10 0.90 12.59 19.58 24.89 39.69

11 1.00 15.67 23.13 32.62 52.25

12 1.20 18.79 28.78 41.48 66.37

13 1.40 21.07 35.86 50.22 78.54

14 1.60 24.51 43.02 58.17 91.87

15 1.80 26.32 47.38 69.39 104.21

16 2.00 27.98 47.62 76.5 112.57

17 2.25 28.43 54.28 82.91 115.48

18 2.50**

30.28 56.84 89.31 121.52

19 2.75 30.28 56.93 89.57 121.77

20 3.00 30.32 56.96 89.76 121.92*MHC ;

**Cmax

54

0

20

40

60

80

100

120

0 0.5 1 1.5 2 2.5 3

C, mol/L

10

2 S

, m

ol/

LT = 303K

T = 313K

T = 323K

T = 333K

Figure 7.1 Effect of sodium salicylate concentration (C) on the

solubility (S) of benzoic acid in water at different

temperatures (T)

Hence, in the concentration region of sodium salicylate between

0.00 and 3.00mol/L, four different characteristics of sodium salicylate as

hydrotrope were observed. It was inactive below MHC of 0.50mol/L, above

which an appreciable increase in the solubility of acids was found up to 1.00

mol/L. Above this concentration, an abnormal solubilization effect of sodium

salicylate was observed up to Cmax of 2.50mol/L, beyond which there is no

further solubilization effect of sodium salicylate.

Hence, sodium salicylate was found to be an effective hydrotrope in

the concentration range between 0.50 and 2.50mol/L towards benzoic acid. It

has been observed that the solubilization effect of sodium salicylate was not a

linear function of the concentration of the hydrotrope solution.

55

A similar trend in the solubilizing effect of sodium salicylate was

observed at increased system temperatures viz. 313, 323, and 333 K. The

values of MHC and Cmax remained unaltered even at higher temperatures.

From Figure 7.1, which shows the effect of sodium salicylate

concentration on the solubility of benzoic acid, it can be observed that in

order to achieve a particular solubility of benzoic acid say i.e., 20.00 x 10-2

mol/L, it is required to maintain the concentration of sodium salicylate in the

aqueous phase at 1.30 mol/L for a system temperature of 303K, 0.90 mol/L

for 313K, 0.80 mol/L for 323K and 0.60 mol/L for 333K. Therefore when the

system temperature is increased, a lesser amount of hydrotrope concentration

is adequate to achieve any particular solubility of benzoic acid.

7.2.1.2 Effect of sodium salicylate on other acids and alizarin

A similar trend in solubilization effect of sodium salicylate has been

observed for other acids namely p-hydroxybenzoic acid, p-nitrobenzoic acid,

cinnamic acid and alizarin. The experimental data for such organic acids-

hydrotrope and alizarin-hydrotrope systems are given in Appendix 2.

From the analysis of the experimental data, it has been observed that

hydrotrope (sodium salicylate) increases the solubility of acids and

alizarin studied significantly. The MHC values of sodium salicylate for

various acids range between 0.40 and 0.60 mol/L. The Cmax values range

between 2.00 and 2.50 mol/L (Table 6.3)

It has also been observed that at increased system temperatures,

lesser hydrotrope concentration is found to be adequate to achieve a particular

solubility of any acid in the presence of sodium salicylate as hydrotrope.

56

7.2.1.3 Effect of sodium benzoate on p-nitrobenzoic acid

Experimental data representing the average of duplicate

determinations on the effect of sodium benzoate on the solubility of

p-nitrobenzoic acid is presented in Table 7.2 and are plotted in Figure 7.2.

Sodium benzoate is one of the hydrotropes used in this study. It has been

observed that the solubility increases significantly only after the addition of

0.30mol/L of sodium benzoate in the aqueous solution for p-nitrobenzoic

acid. This concentration is referred to as the Minimum Hydrotrope

Concentration (MHC). Therefore, it is evident that hydrotropy was

operational above the MHC of sodium benzoate which also depends on the

nature of solute.

The solubilization effect varies with concentration of hydrotropes.

This increasing trend is maintained only up to a certain concentration of

sodium benzoate in the aqueous solution, beyond which there is no

appreciable increase in the solubility of p-nitrobenzoic acid. This

concentration of sodium benzoate (hydrotrope) in the aqueous solution is

referred to as the Maximum Hydrotrope Concentration (Cmax). From the

analysis of the experimental data, it is observed that further increase in

hydrotrope concentration beyond Cmax does not bring any appreciable increase

in the solubility of the acids even up to 3.00 mol/L of sodium benzoate in the

aqueous solution. Both MHC and Cmax values of hydrotrope remained

unaltered at increased system temperatures.

57

Table 7.2 Effect of sodium benzoate concentration (C) on the

solubility (S) of p-nitrobenzoic acid in water

S.NoC,

mol/L

103 S, mol/L

T = 303K T = 313K T = 323K T = 333K

1 0.00 2.09 2.54 3.06 3.65

2 0.10 2.16 2.51 3.14 3.61

3 0.20 2.20 2.68 3.21 3.72

4 0.30* 2.97 3.91 4.79 5.21

5 0.40 3.72 5.61 6.83 8.19

6 0.50 4.9 8.34 9.2 13.73

7 0.60 7.5 9.95 14.05 17.93

8 0.70 10.1 11.73 15.41 19.38

9 0.80 11.58 13.18 18.79 23.64

10 0.90 14.39 17.32 21.62 26.57

11 1.00 16.60 20.79 26.8 30.91

12 1.20 17.70 24.15 32.74 40.63

13 1.40 22.00 28.19 36.18 45.68

14 1.60 24.5 33.71 39.12 54.67

15 1.80 26.08 37.25 47.49 60.31

16 2.00 27.34 38.36 50.47 65.72

17 2.25 28.31 40.08 52.82 71.68

18 2.50**

29.54 41.76 56.91 76.71

19 2.75 29.69 41.87 57.16 76.87

20 3.00 29.74 42.01 57.21 76.94

*MHC ;

**Cmax

58

From the Figure 7.2, it can further be observed that, in order to

achieve the particular solubility of p-nitrobenzoic acid, say 20.0 10-3

mol/L,

the sodium benzoate concentration should be 1.30 mol/L at 303 K,

1.00 mol/ L at 313 K, 0.82 mol/L at 323 K and 0.70 mol/L at 333K in the

aqueous solution. Thus it can be seen that as the system temperature

increases, the concentration of sodium benzoate required in the aqueous phase

to achieve a particular solubility of p-nitrobenzoic acid decreases. It has also

been observed that the solubilization effect of sodium benzoate was not a

linear function of the concentration of the sodium benzoate. The

solubilization effect of sodium benzoate increases with increase in hydrotrope

concentration and also with system temperature.

0

10

20

30

40

50

60

70

80

90

0 0.5 1 1.5 2 2.5 3

C, mol/L

10

3 S

, m

ol/

L

T = 303K

T = 313K

T = 323K

T = 333K

Figure 7.2 Effect of sodium benzoate concentration (C) on the

solubility (S) of p-nitrobenzoic acid in water at different

temperatures (T)

59

7.2.1.4 Effect of sodium benzoate on other acids and alizarin

A similar trend in solubilization effect of sodium benzoate has been

observed for other acids namely benzoic acid, p-hydroxybenzoic acid,

cinnamic acid and alizarin. The experimental data for such organic acids-

hydrotrope and alizarin-hydrotrope systems are given in Appendix 2.


hydrotrope (sodium benzoate) increases the solubility of acids and

alizarin studied significantly. The MHC values of sodium benzoate for

various acids range between 0.30 and 0.50 mol/L. The Cmax values range

between 2.25 and 2.50 mol/L (Table 6.3).

Similar to that of sodium salicylate it has also been observed that at

increased system temperatures, lesser hydrotrope concentration is found to be

adequate to achieve a particular solubility of any acid in the presence of

sodium benzoate as hydrotrope.

7.2.1.5 Effect of potassium p-toluene sulfonate (KPTS) on the solubility

of alizarin

Experimental data of the effect of potassium p-toluene sulfonate

(KPTS) on the solubility of alizarin is presented in Tables 7.3 and is plotted in

Figures 7.3. It was observed that the solubility of alizarin did not show any

appreciable increase up to addition of 0.30mol/L of KPTS. On subsequent

increase in the concentration of KPTS above0.30 mol/L, the solubility of

alizarin in water was found to increase significantly. This concentration of

KPTS in the aqueous phase, 0.30 mol/L is termed the Minimum Hydrotrope

Concentration (MHC), which is the minimum required KPTS concentration in

the aqueous phase to effect significant increase in the solubility of alizarin in

water.

60

It has been observed that the MHC of KPTS in the aqueous phase

does not vary at increased temperatures of 313, 323 and 333 K. In the present

case, a clear increasing trend in the solubility of alizarin was observed above

the MHC of KPTS. This increase in solubility of alizarin is maintained up to

2.50mol/L of KPTS in the aqueous phase, beyond which there is no

appreciable increase in its solubility. This concentration of KPTS in aqueous

phase is referred to as the maximum hydrotrope concentration (Cmax).

From the analysis of the experimental data, it is observed that

further increase in hydrotrope concentration beyond Cmax does not bring any

appreciable increase in the solubility of alizarin even up to 3.00mol/L. Similar

to the MHC values, the Cmax values of hydrotropes also remained unaltered

with increase in system temperature.

In the concentration range of KPTS between 0.00mol/L and

3.00mol/L, three different regions were obtained. It was inactive below the

MHC of 0.30mol/L, above which an appreciable increase in the solubility was

found up to Cmax of 2.50mol/L, a state beyond which there is no further

solubilization effect of the hydrotrope. Therefore, from Figure7.3 it was

observed that the KPTS was found to be an effective hydrotrope in the

concentration range between 0.30mol/L and 2.50mol/L. It has also been

observed that the solubilization effect of KPTS was not a linear function of

the concentration of the KPTS solution. A similar trend in the solubilizing

effect of KPTS was observed at increased system temperatures viz. 313, 323,

and 333 K.

61

Table 7.3 Effect of potassium p-toluene sulfonate concentration (C) on

the solubility (S) of alizarin in water

S.NoC,

mol/L

103 S, mol/L

T = 303K T = 313K T = 323K T = 333K

1 0.00 1.32 1.36 1.39 1.44

2 0.10 1.34 1.62 1.87 2.05

3 0.20 1.42 1.71 1.92 2.14

4 0.30* 2.59 3.01 3.38 3.75

5 0.40 3.82 5.78 6.32 7.64

6 0.50 4.81 7.82 8.54 9.65

7 0.60 5.96 9.65 10.26 13.82

8 0.70 6.85 12.36 13.29 20.83

9 0.80 7.84 16.01 17.05 24.33

10 0.90 9.65 20.32 25.17 39.61

11 1.00 13.82 23.48 32.09 46.18

12 1.20 17.43 38.82 49.31 60.13

13 1.40 25.52 48.13 62.29 80.85

14 1.60 32.71 56.31 80.08 97.26

15 1.80 48.22 71.14 90.57 110.71

16 2.00 68.73 91.39 109.19 134.18

17 2.25 76.80 105.10 121.02 140.01

18 2.50**

90.58 113.64 129.38 148.71

19 2.75 90.82 113.71 129.47 148.73

20 3.00 91.05 114.14 130.02 149.05

*MHC ;

**Cmax

62

0

20

40

60

80

100

120

140

160

0 0.5 1 1.5 2 2.5 3

C, mol/L

10

3 S

, mo

l/L

T = 303K

T = 313K

T = 323K

T = 333K

Figure 7.3 Effect of potassium p-toluene sulfonates concentration (C) on the

solubility (S) of alizarin in water at different temperatures (T)

7.2.1.6 Other hydrotropes

A similar set of experimentations has been carried out using

different hydrotropes namely nicotinamide and urea for various acids and

alizarin. Such experimental data are presented in Appendix 2.

7.2.1.7 Effect of system temperature on the solubility in the presence of

hydrotropes

The temperature dependence of benzoic acid solubility in different

aqueous hydrotrope solutions are described by the modified Apelblat equation

ln x = A + B/T + C lnT (7.1)

where x is the solubility of benzoic acid

T - absolute temperature

A, B and C - model parameters

63

The values of parameters A, B, C and the corresponding root-mean-

square deviation are listed in the Table 7.4.

Similarly the values of parameters A, B, C and the corresponding

root-mean-square deviation for other acids and alizarin in various

hydrotropes solutions has been determined at different system temperature are

presented in Appendix 3.

Table 7.4 Apelblat equation parameters A, B, and C for correlation of

benzoic acid data in hydrotrope solutions

C, mol/L A B C RMSD × 103

Sodium Salicylate

0.00 -168.83 5802.42 24.89 0.020

1.00 -165.41 3996.20 25.59 0.155

2.00 -156.94 3414.12 24.58 0.354

2.50 -157.20 3693.33 24.49 0.820

Sodium Benzoate

0.00 -168.83 5802.42 24.89 0.020

1.00 -147.4 3751.69 22.55 0.110

2.00 -138.63 2946.84 21.59 0.259

2.50 -132.03 2425.18 20.75 0.350

Nicotinamide

0.00 -168.83 5802.42 24.89 0.020

1.00 -123.94 1631.37 19.60 0.118

2.00 -119.74 1133.85 19.23 0.206

2.50 -116.48 1164.87 18.64 0.232

Urea

0.00 -168.83 5802.42 24.89 0.020

1.00 -156.67 3633.64 24.15 0.086

2.00 -136.02 1993.86 21.53 0.115

2.50 -126.68 1568.60 20.09 0.145

64

7.2.2 MHC and Cmax Values of Hydrotropes

As pointed out earlier in chapter 6, the MHC value seems to depend

on the hydrophilicity of a hydrotrope. The Cmax values of hydrotropes for

various acids used in this work range between 2.00 and 2.50 mol/L. The MHC

and Cmax values of a hydrotrope remained unaltered at increased system

temperatures (Table 6.2 and 6.3).

7.2.3 Solubility Enhancement Factor of Organic Acids and Alizarin

The solubility enhancement factor ( s) values effected by various

hydrotropes for benzoic acid are presented in Table 7.5. In all cases the values

of s of benzoic acid increases with increase in system temperature. The

highest s value of 19.98 is reported in the case of sodium salicylate at 333K.

The analysis of the s values for this system shows that sodium salicylate

serves as the effective hydrotrope at all temperatures to bring maximum

solubilization of benzoic acid.

The s values of p-hydroxybenzoic acid in the presence of various

hydrotropes at different temperatures are given in Table 7.6. The highest s

value obtained is 27.20 in the presence of sodium salicylate at 333K. The

values of s increase substantially with increase in system temperature.

The effect of various hydrotropes on s for p-nitrobenzoic acid is

presented in Table 7.7. From the table it can be observed that sodium

benzoate brings maximum s value of 21.08 at 333K.

Table 7.8 presents the s values for cinnamic acid in the presence of

various hydrotropes at different temperatures. The values of s increase with

increase in system temperature in all cases. Sodium benzoate was found to be

an effective hydrotrope to bring maximum s value of 14.84 at 333K.

65

The s values effected by various hydrotropes towards alizarin are

given in Table 7.9. In this case, potassium p-toluene sulfonate serves as an

effective hydrotrope for use at all temperatures with maximum s of 103.27 at

333K.

It has been observed that, the solubility enhancement factors

effected by sodium salicylate and sodium benzoate is much higher for organic

acids. The hydrotrope potassium p-toluene sulfonate brings maximum

solubility enhancement factor for alizarin.

Table 7.5 Solubility enhancement factor of benzoic acid

HydrotropesMaximum solubility enhancement factor ( s)

T = 303 K T = 313 K T = 323 K T = 333 K

Sodium salicylate 9.43 14.07 16.16 19.98

Sodium benzoate 6.63 9.35 11.25 13.61

Nicotinamide 3.34 5.32 6.74 8.48

Urea 2.85 4.07 5.59 6.98

Table 7.6 Solubility enhancement factor of p-hdyroxybenzoic acid


T = 303 K T = 313 K T = 323 K T = 333 K


Sodium benzoate 6.48 8.92 10.49 13.74

Nicotinamide 3.71 5.28 6.64 7.98

Urea 2.40 3.54 4.35 5.74

66

Table 7.7 Solubility enhancement factor of p-nitrobenzoic acid


T = 303 K T = 313 K T = 323 K T = 333 K

Sodium benzoate 14.23 16.54 18.70 21.08


Nicotinamide 5.12 6.63 7.13 8.07

Urea 3.64 4.58 5.62 6.26

Table 7.8 Solubility enhancement factor of cinnamic acid


T = 303 K T = 313 K T = 323 K T = 333 K

Sodium benzoate 7.23 10.52 12.65 14.84


Nicotinamide 3.52 4.33 5.18 6.38

Urea 2.85 3.65 4.71 5.95

Table 7.9 Solubility enhancement factor of alizarin


T = 303 K T = 313 K T = 323 K T = 333 K

Potassium

p-toluene sulfonate68.62 83.56 93.08 103.27


Sodium benzoate 9.72 14.15 20.19 27.03

Nicotinamide 4.16 4.96 5.77 6.41

Urea 3.55 4.51 5.63 6.19

67

7.2.4 Effect of System Temperature on the Solubility Enhancement

Factors of Acids and Alizarin in the Presence of Hydrotropes

The effect of hydrotropes on solubility enhancement factor, s of

acids and alizarin at 303K is presented in Table 7.10. The solubility

enhancement factor, s of acids were found to be higher in the presence of

sodium salicylate and sodium benzoate as hydrotrope. Hence for the system

temperature of 303K, sodium salicylate can be preferred for benzoic acid and

p-hydroxybenzoic acid whereas for p-nitrobenzoic acid and cinnamic acid,

sodium benzoate acts as an effective hydrotrope. The maximum enhancement

factor for alizarin is obtained in the presence of potassium p-toluene sulfonate

as hydrotrope followed by sodium salicylate, sodium benzoate and

nicotinamide. For all organic acids, there is difference in the values of s

effected by sodium salicylate, sodium benzoate, nicotinamide and urea, with

sodium salicylate and sodium benzoate having an upper level values.

Table 7.11 to 7.13 presents the effect of hydrotropes on s of acids

at different temperature ranges from 313K-333K. From the analysis of

experimental data it has been observed that for benzoic acid and p-

hydroxybenzoic acid, sodium salicylate shows the maximum s value where

as for p-nitrobenzoic acid and cinnamic acid, sodium benzoate effected

maximum solubility enhancement The effect of hydrotropes on solubility

enhancement factor at different temperatures for acids and alizarin are as

same as that observed at temperature 303K.

68

Table 7.10 Effect of hydrotropes on s of acids at 303K

Hydrotropes

Maximum enhancement factor for solubility ( s)

Benzoic acidp-Hydroxybenzoic

acidp-Nitrobenzoic acid Cinnamic acid


Sodium benzoate 6.63 6.48 9.61 7.23

Nicotinamide 3.34 3.71 5.12 3.52

Urea 2.85 2.40 3.64 2.85


Hydrotropes

Maximum enhancement factor for solubility ( s)

Benzoic acidp-Hydroxybenzoic

acidp-Nitrobenzoic acid Cinnamic acid


Sodium benzoate 9.35 8.92 11.56 6.86

Nicotinamide 5.32 5.28 6.63 4.33

Urea 4.07 3.54 4.58 3.65

69


HydrotropesMaximum enhancement factor for solubility ( s)

Benzoic acid p-Hydroxybenzoic acid p-Nitrobenzoic acid Cinnamic acid


Sodium benzoate 11.25 10.49 13.28 8.72

Nicotinamide 6.74 6.64 7.13 5.18

Urea 5.59 4.35 5.62 4.71


HydrotropesMaximum enhancement factor for solubility ( s)

Benzoic acid p-Hydroxybenzoic acid p-Nitrobenzoic acid Cinnamic acid


Sodium benzoate 13.61 13.74 21.08 11.25

Nicotinamide 8.48 7.98 8.07 6.38

Urea 6.98 5.74 6.26 5.95

70

7.2.5 Identification of the Best Hydrotrope for Various Acids and

Alizarin

The maximum solubility enhancement factors for acids and

alizarin effected by various hydrotropes are given in Table 7.14. For benzoic

acid, and p-hydroxybenzoic acid, sodium salicylate is the best one among the

hydrotropes used at the hydrotrope concentration of 2.50mol/L at 333K. In

the case of p-nitrobenzoic acid and cinnamic acid, sodium benzoate is the best

hydrotrope at the concentration of 2.50mol/L at 333K. For alizarin, potassium

p-toluene sulfonate is the best one at 2.50mol/L at 333K.

The order of increase in the solubilization of acids and alizarin in

the presence of hydrotropes based on s value was found to be

Alizarin > p-Hydroxybenzoic acid > p-Nitrobenzoic acid >

Benzoic acid > Cinnamic acid.

Table 7.14 Maximum s of acids and alizarin in the presence of

hydrotropes

Solutes s Hydrotrope C, mol/L T, K

Benzoic acid 19.98 Sodium salicylate 2.50 333

p-Hydroxybenzoic acid 27.20 Sodium salicylate 2.50 333

p-Nitrobenzoic acid 21.08 Sodium benzoate 2.50 333

Cinnamic acid 16.28 Sodium benzoate 2.50 333

Alizarin 103.27 Potassium p-toluene

sulfonate

2.50 333

71

7.3 EFFECT OF HYDROTROPES ON MASS TRANSFER

COEFFICIENT OF ORGANIC ACIDS AND ALIZARIN

7.3.1 Introduction

In the previous section, the effect of hydrotropes on the solubility of

acids and alizarin has been discussed. The solubility enhancement factor for

each acid-hydrotrope and alizarin-hydrotrope system was also determined.

These enhancements in solubility of acids and alizarin were obtained after

attaining equilibration using a thermostatic bath method. This section

discusses the effect of hydrotropes on mass transfer coefficient of organic

acids and alizarin in the presence of hydrotropes. An agitated vessel was used

for this purpose.

A time limit of say 600, 1200, 1800 and 2400 seconds has been

fixed for each experimentation. The speed of agitation was fixed at 600 rpm.

The concentration of the acid ‘Cb’ in hydrotrope solutions at any fixed time‘t’

was determined. For each run, the relative solubility Cb/C* has been estimated

where C* is the equilibrium solubility at the same acid-hydrotrope system at

any particular hydrotrope concentration in the aqueous phase obtained after

equilibration using thermostatic bath method. These values were used to

determine the mass transfer coefficient, kLa.

7.3.2 Benzoic Acid – Sodium Salicylate System

The mass transfer coefficient of benzoic acid in the absence of any

hydrotrope is 7.14 x 10-4

s-1

. The ability of hydrotropes such as sodium

salicylate, sodium benzoate, nicotinamide and urea as potential hydrotropes to

increase the mass transfer coefficient of benzoic acid was investigated. The

influence of different hydrotropes concentration on mass transfer coefficient

of acids has been determined for each case.

72

7.3.2.1 Sodium salicylate

From the solubility determination part of the experimentation, the

MHC and Cmax values of benzoic acid-sodium salicylate system were

observed to be 0.50 and 2.50 mol/L respectively. For mass transfer studies,

five different hydrotrope concentrations i.e. 0.50, 0.80, 1.00, 1.40 and

2.50 mol/L were randomly selected within the range of MHC and Cmax values.

Mass transfer studies were carried out for each hydrotrope concentration in

the aqueous phase. The effect of sodium salicylate as hydrotrope on the mass

transfer coefficient of benzoic acid at different hydrotrope concentrations is

given in Table 7.15.

From Table 7.15, it can be seen that a threshold value i.e., 0.50

mol/L which is nothing but MHC of sodium salicylate for benzoic acid is to

be maintained to obtain significant enhancement in the mass transfer

coefficient of benzoic acid, as observed in the case of solubility

determinations. The mass transfer coefficient of benzoic acid increases with

increase in sodium salicylate concentrations. Beyond 2.50 mol/L of sodium

salicylate, there is no appreciable increase in mass transfer coefficient for

benzoic acid, as observed in the case of solubility determinations.

The maximum enhancement in mass transfer coefficient of benzoic

acid in the presence of sodium salicylate as hydrotrope in the aqueous phase

was found to be 12.07. These observations suggest the fact that increase in

mass transfer coefficient is found to occur upon increased solubilization.

A similar trend in mass transfer coefficient enhancement ( mtc) of

benzoic acid has been observed for other hydrotropes namely sodium

benzoate, nicotinamide and urea (Tables 7.16 to 7.18).

73

Table 7.15 Effect of sodium salicylate concentration (C) on mass

transfer coefficient (kLa) of benzoic acid

Sl.No. C, mol/L 104 kLa, s

-1 Enhancement factor for mass

transfer coefficient ( mtc)

1 0.00 7.14 -

2 0.50*

19.22 2.69

3 0.80 25.25 3.54

4 1.00 38.60 5.41

5 1.40 52.68 7.38

6 2.50**

86.21 12.07

7 3.00 87.21 12.21

*MHC ;

**Cmax

Table 7.16 Effect of sodium benzoate concentration (C) on mass

transfer coefficient (kLa) of benzoic acid


-1

Enhancement factor for

mass transfer coefficient

mtc)

1 0.00 7.14 -

2 0.20 7.19 1.01

3 0.40*

16.61 2.33

4 0.80 19.24 2.69

5 1.40 28.94 4.05

6 2.00 45.95 6.44

7 2.50**

55.42 7.76

8 3.00 55.71 7.80

*MHC ;

**Cmax

74

Table 7.17 Effect of nicotinamide concentration (C) on mass transfer

coefficient (kLa) of benzoic acid


-1



mtc)

1 0.00 7.14 -

2 0.20 7.17 1.00

3 0.60*

14.94 2.09

4 0.80 21.16 2.96

5 1.20 27.54 3.86

6 1.80 33.98 4.76

7 2.25**

36.84 5.16

8 3.00 37.51 5.25

*MHC ;

**Cmax

Table 7.18 Effect of urea concentration (C) on mass transfer coefficient

(kLa) of benzoic acid


-1



mtc)

1 0.00 7.14 -

2 0.20 7.19 1.01

3 0.60*

9.37 1.31

4 1.20 15.87 2.22

5 1.40 17.65 2.47

6 1.80 22.79 3.19

7 2.25**

27.68 3.88

8 3.00 28.98 4.06

*MHC ;

**Cmax

75

Table 7.19 Effect of hydrotropes on mtc of acids and alizarin

Hydrotropes

Maximum mtc

Benzoic

acid

p-Hydroxybenzoic

Acid

p-Nitrobenzoic

Acid

Cinnamic

acidAlizarin

Sodium

salicylate12.07 11.31 10.10 6.34 30.50

Sodium

benzoate7.76 8.30 15.20 9.26 21.94

Nicotinamide 5.16 4.62 5.43 2.99 4.56

Urea 3.88 2.87 3.88 3.45 3.61

Potassium

p-toluene

sulfonate

- - - - 58.71

7.3.2.2 Other acids and alizarin

A similar set of experimentations has been carried out for other

acids namely p-hydroxybenzoic acid, p-nitrobenzoic acid, cinnamic acid and

alizarin using different hydrotropes. Such experimental data are presented in

Appendix 4. The maximum enhancement factor for mass transfer coefficient

of various acids namely benzoic acid, p-hydroxybenzoic acid, p-nitrobenzoic

acid, cinnamic acid and alizarin are presented in Table 7.19. It can be

observed that sodium salicylate serves as the best hydrotrope for benzoic acid

and p-hydroxybenzoic acid in terms of enhancing mass transfer coefficient.

For p-nitrobenzoic acid and cinnamic acid, sodium benzoate gives maximum

enhancement for mass transfer coefficient.

The range of maximum mtc values is between 9.26 and 58.71 with

highest value of 58.71 observed for alizarin-potassium p-toluene sulfonate

system at maximum hydrotrope concentration of 2.50mol/L in the aqueous

phase (Table 7.20). The hydrotrope potassium p-toluene sulfonate was used

only for alizarin and it was selected based on the structure of alizarin. This

table also gives the best one among the four hydrotropes used to bring

maximum mtc of various acids and alizarin.

76

Table 7.20 Maximum mtc of acids and alizarin in the presence of

hydrotropes

SoluteMaximum

mtcHydrotrope

Cmax,

mol/L

Benzoic acid 12.07 Sodium salicylate 2.50

p-Hydroxybenzoic acid 11.31 Sodium salicylate 2.50

p-Nitrobenzoic acid 15.20 Sodium benzoate 2.50

Cinnamic acid 9.26 Sodium benzoate 2.50

Alizarin 58.71 Potassium p-toluene sulfonate 2.50

7.4 EFFECTIVENESS OF HYDROTROPES

The ‘effectiveness factor’ of each hydrotrope with respect to a series

of acids at different system temperatures and alizarin at 303K has been

determined by analyzing the experimental solubility data for each case,

applying the model suggested by Setschenow and later modified by Pathak

and Gaikar (1993) as given by the Equation (7.2).

log10 [S/Sm] = Ks[Cs-Cm] (7.2)

where S and Sm are the solubilities of the solute at any hydrotrope

concentration (Cs) and minimum hydrotrope concentration (Cm) respectively.

The Setschenow constant Ks, can be considered as a measure of the

effectiveness of a hydrotrope at any given conditions of hydrotrope

concentration and system temperature.

The Setschenow constant values of hydrotropes, namely sodium

salicylate, sodium benzoate, nicotinamide and urea for each acid and alzarin

at different system temperatures are listed in Table 7.21 to 7.25.

77

Table 7.21 Setschenow constant values of sodium salicylate

Temperature, KSetschenow constant, Ks

Benzoic acid p-Hydroxybenzoic acid p-Nitrobenzoic acid Cinnamic acid Alizarin

303 0.376 0.381 0.446 0.287 0.558

313 0.438 0.500 0.458 0.343 0.593

323 0.474 0.571 0.480 0.393 0.628

333 0.502 0.611 0.513 0.436 0.671

Table 7.22 Setschenow constant values of sodium benzoate



303 0.313 0.338 0.455 0.304 0.508

313 0.396 0.467 0.468 0.390 0.537

323 0.428 0.537 0.489 0.430 0.556

333 0.465 0.592 0.531 0.454 0.606

78

Table 7.23 Setschenow constant values of nicotinamide



303 0.229 0.303 0.362 0.278 0.336

313 0.316 0.432 0.406 0.331 0.348

323 0.378 0.515 0.427 0.372 0.356

333 0.428 0.543 0.506 0.412 0.366

Table 7.24 Setschenow constant values of urea



303 0.193 0.225 0.277 0.232 0.271

313 0.258 0.342 0.327 0.259 0.309

323 0.362 0.419 0.367 0.300 0.321

333 0.400 0.492 0.401 0.340 0.328

79

Table 7.25 Setschenow constant values of KPTS


303 313 323 333

Alizarin 0.702 0.717 0.720 0.728

From Table 7.21 it is seen that the Ks values of sodium salicylate

with respect to various acids range between 0.0.287 and 0.671. The Ks value

increases with increase in system temperature. The highest value of 0.671 has

been observed for alizarin at 333 K.

For the hydrotrope, sodium benzoate Ks values range between 0.304

and 0.606 as given in Table 7.22. It can be seen that only at increased system

temperatures, the effectiveness factors (Ks) were found to be at higher levels.

The highest value has been observed to be 0.606 at 333K for alizarin.

When nicotinamide was used as a hydrotrope, the values of Ks were

found to be in the range between 0.229 and 0.543 as shown in Table 7.23. It

can be seen that the Ks value was found to be in the increasing order with

respect to temperature. The highest value has been observed as 0.543 at 333K

for p-hydroxybenzoic acid.

Table 7.24 gives the range of Ks value of urea between 0.193 and

0.492. There is a significant increase in Ks values with increase in system

temperature for all cases. The highest value has been observed to be 0.492 for

p-hydroxybenzoic acid at 333K.

The hydrotrope potassium p-toluene sulfonate was used as a

hydrotrope for alizarin, the values of Ks were found to be in the range

between 0.702 and 0.728 as shown in Table 7.25. The highest value of 0.728

80

for alizarin has been observed at 333K which is higher than the effectiveness

of sodium salicylate observed for alizarin.

Hence by applying the Setschenow model, the order of effectiveness

of hydrotropes based on Ks value for benzoic acid and p-hydroxybenzoic acid

was found to be

Sodium salicylate > Sodium benzoate > Nicotinamide > Urea

For p-nitrobenzoic acid and cinnamic acid the order of effectiveness

of various hydrotrope is

Sodium benzoate > Sodium salicylate > Nicotinamide > Urea

For the alizarin, the order of effectiveness of various hydrotropes is

Potassium p-toluene sulfonate > Sodium salicylate >

Sodium benzoate > Nicotinamide > Urea

7.5 ASSOCIATION CONSTANTS (K2 AND Khs) FROM

ASSOCIATION MODEL

In this study the aggregation behavior of hydrotrope and the

solubilization of organic acids and alizarin are further explored. Since

aggregation of the hydrotrope is a pre-requisite for the solubilization of a

solute, an association model is used. The model attempts to explain the

increase in the solubility of a hydrophobic solute in an aqueous solution of a

hydrotrope in terms of the associations between hydrotrope–hydrotrope and

hydrotrope–solute molecules.

An association model of hydrotropic solubilization is used to

represent the solubilization of acids and alizarin in hydrotrope solutions. The

81

model considers stepwise aggregation of the hydrotrope molecules and

solubilization of the solute through coaggregation with the hydrotropic

aggregates.

The self-aggregation of a hydrotrope is favored by the hydrophobic

effect which is governed by its hydrocarbon structure and is opposed by the

electrostatic repulsion between the charged head groups giving rise to an

optimum aggregation number of the self-assemblies of the hydrotrope.

The association constant for an n-mer of hydrotrope with a

monomer is related to the dimerization constant (K2, L/mol), i.e., Kn = K2/n.

The total concentration of the hydrotrope (Cs) and the monomer concentration

(H1) can be related by the following Equations (7.3):

1]-e[2HC 12HK

1s (7.3)

A solute molecule can reside between the hydrotrope molecules and

reduce the electrostatic repulsion between the charged groups of the

hydrotrope molecules, effectively compacting the aggregate structure and

providing geometrical constraint to the incorporation of more solute

molecules into the same aggregate. Since most solubility studies with

hydrotrope solutions show a sigmoidal nature of the solubility curve with

hydrotrope concentration, it is appropriate to assume a finite capacity of a

hydrotrope aggregate to solubilize the solute. Considering that the association

constant for incorporation of a solute molecule into an n-mer of hydrotrope

decreases with every new addition of a solute molecule, hydrotrope n-mer is

assumed to take up a maximum of (n-1) solute molecules.

The total amount of the solute associated with the hydrotrope

aggregates, under the assumption that hydrotrope aggregate-solute association

82

constant decreases with increase in number of solute molecules (j) in the

coaggregate (Knj = Khs/j), is given by Equation (7.4).

)HK(1-e][SK

K2S 12

HK

1

2

hs

T12 (7.4)

The amount of solute associated with the hydrotrope

(Equation (7.4)) can be related to the total concentration of the hydrotrope

(Equation (7.3)), which is a measurable quantity. These two equations can be

used to estimate the values of the association parameters K2 and Khs from the

solubility data. They characterize the hydrotrope-hydrotrope and hydrotrope-

solute associations, respectively.

The experimental solubility data of acids and alizarin was fitted into

the association model (Equations (7.3) and (7.4)). The Equations (7.3) and

(7.4) are nonlinear and a nonlinear least-squares method has been adopted.

Equation (7.3) can be inverted into a polynomial where the monomer

concentration (H1) can be obtained in terms of total hydrotrope concentration

(Cs). This concentration can be substituted into Equation (7.4) to estimate the

relevant parameters such as K2 and Khs, which represent the hydrotrope-

hydrotrope and hydrotrope-solute associations respectively.

For the hydrotrope, sodium salicylate K2 values range between

0.517 and 2.947 L/mol and Khs values range between 18.54 and 325.45 L/mol

as given in Table 7.26. Both K2 and Khs values increases with increase in

system temperature for all acids. The highest value of K2 has been observed to

be 2.947 L/mol at 333K for alizarin. Similarly the highest value of Khs is

325.45 L/mol has been observed for alizarin at 333K.

83

Similarly the association constants for other acids and alizarin in

various hydrotropes solutions has been determined at different system

temperatures (Appendix 5).

Although the hydrotrope aggregates are formed in aqueous

solutions, their aggregation tendency is much weaker than that of solute-

hydrotrope coaggregation. With increase in temperature, the association

constants (K2 and Khs) were also found to increase. It seems that the

temperature increase effect a significant change in the aggregate structures,

thereby causing more solute to be solubilized in the hydrotrope solutions.

Table 7.26 Association constants (K2, Khs) for solute and sodium

salicylate for association model of hydrotropy

Temperature,

K

K2, Khs, L/mol

Benzoic

acid

p-Hydroxybenzoic

acid

p-Nitrobenzoic

acid

Cinnamic

acidAlizarin

K2 Khs K2 Khs K2 Khs K2 Khs K2 Khs

303 0.641 45.32 1.310 133.98 0742 5.320 0.030 1.320 1.854 248.63

313 0.783 59.81 1.536 157.28 0.805 10.354 0.057 2.528 2.471 289.12

323 0.865 62.35 1.451 178.54 0.927 12.043 0.062 3.089 2.623 305.84

333 0.943 78.45 2.054 186.95 1.781 15.608 0.063 5.762 2.947 325.45

7.6 MECHANISM OF HYDROTROPIC PHENOMENON

The advent of Minimum Hydrotrope Concentration (MHC) has

opened up more avenues for the experimental studies on various solutes in

different hydrotrope solutions. Previous workers have suggested various

theories like salting-in-effect, complex formation, cosolvency, association of

hydrotrope molecules, intermolecular interactions etc., for the contribution of

hydrotropic effect towards many organic and inorganic solutes. However no

consistent idea on the mechanism of hydrotropy has been arrived until now.

84

In the present work, a comprehensive study on the effect of various

hydrotropes on the solubility and mass transfer coefficient of a series of

organic acids has been carried out. It has been ascertained that in the case of

organic acids, a certain minimum concentration of hydrotrope in the aqueous

was found essential to observe a significant increase in the solubility.

Therefore, it has become quite clear that whatever be the type of

hydrotrope that is being used in the aqueous phase, a minimum concentration

of hydrotrope is necessary to initiate the solubilization activity of a

hydrotrope.


the solubility of the solute increases with increase in hydrotrope concentration

and the solubilizing effect of hydrotropes is not a linear function with the

hydrotrope concentration. It was also seen that MHC values of various

hydrotropes used in this study range between 0.30 to 0.60 mol/L with respect

to different organic acids. In other words, for the same aqueous phase

concentration, different number of hydrotrope molecules is required to form

aggregates at MHC values. This range of critical MHC values may be due to

the difference in the hydrophilic nature of the hydrotropes in the aqueous

phase. Such a significant concentration of hydrotrope required in the aqueous

phase suggests the formation of a certain complex arrangement of the

hydrotrope molecules in the aqueous phase.

7.6.1 Solution Properties of Hydrotropes

In order to explain the theory of complex arrangement, a study on

the solution properties like viscosity, specific gravity, surface tension, specific

conductance and refractive index of hydrotropes for range of hydrotrope

concentrations (0-2.0 mol/L) has been carried out. Figures 7.4 to 7.10 show

the plot of viscosity, specific gravity, surface tension, specific conductance

85

and refractive index of hydrotrope solution vs hydrotrope concentration for

different hydrotropes used.

From the Figures it can be seen that the trend in the change of

solution properties with hydrotrope concentrations is a linear one up to the

critical concentration corresponding to MHC values, after which a distinct

deviation from linearity has been observed.

The positive deviation in the viscosity plot (Figure 7.4) indicates

that aggregate formation is associated with an increase in viscosity of

hydrotrope concentration.

The plot of specific gravity versus hydrotrope concentration showed

a negative deviation (Figure 7.5) that indicates an increase in partial molal

volume upon aggregation, and this increase in volume may be due to

expansion of the hydrocarbon portion of the molecule or its partial removal

from the high compressive force of water.

The surface tension plot (Figure 7.6) showed a moderate decrease in

surface tension on increasing the hydrotrope concentration as hydrotropes are

not surface active agents. The deviation from linearity in specific conductance

plot (Figure 7.7) is strongly indicative of molecular aggregation.

The plot of refractive index versus hydrotrope concentration (Figure

7.8) showed negative deviation. It was revealed from different studies that

at lower hydrotrope concentration, there were weak ionic interactions while at

higher hydrotrope concentration, the molecular aggregation seems to be the

possible mechanism of hydrotropic solubilization. Therefore, it can be

concluded that the significant solubilizing effect of hydrotropes above MHC

may be due to the fact that hydrotrope molecules probably associate into

organized aggregates at this critical concentration. It may be suggested that

86

the deviation from linearity of solution properties observed is an indication of

aggregate formation, when the concentration surpasses this critical value. In

other words, this deviation may be considered to be the characteristic of

hydrotropic solubilization.

Hence, the formation of aggregates of hydrotrope molecules with

the attainment of MHC can be taken as a pre-requisite to display this

phenomenon.

It may be further assumed that the formation of such aggregates

creates a new surface environment with different solution properties like

viscosity, specific gravity, surface tension, specific conductance and refractive

index. This has been indicated in the study on solution properties also.

Possibly the change in surface tension and hence polarity at MHC enable the

solute molecules to clinch to MHC aggregates to be retained in the aqueous

phase. Such critical surface-active properties of hydrotrope aggregates seem

to initiate the solubilization effect of hydrotropes.

The increase in the solubilizing effect with increase in hydrotrope

concentration may be due to the more number of such aggregates available for

interaction with solute molecules at the existing conditions of the aqueous

phase.

Further formation of hydrotrope aggregates with increased

hydrotrope concentration in the aqueous phase depends on the availability of

water molecules also, since by hydration theory, every water molecule forms

associated structure among themselves and influences other polar substances

in it to form similar association of molecules.

87

0.6

0.8

1

1.2

1.4

1.6

1.8

2

2.2

0 0.5 1 1.5 2

Hydrotrope concentration, mol/L

Vis

co

sity

, cP

Urea

NicotinamideSodium benzoate

Sodium salicylate

Figure 7.4 Plot of viscosity versus hydrotrope concentration for

different hydrotropes

0.95

1

1.05

1.1

1.15

1.2

1.25

1.3

0 0.5 1 1.5 2


Sp

ecif

ic g

ra

vit

y

Urea

NicotinamideSodium benzoate

Sodium salicylate

Figure 7.5 Plot of specific gravity versus hydrotrope concentration for


88

62

63

64

65

66

67

68

69

70

71

0 0.5 1 1.5 2


10

3 S

urfa

ce

ten

sio

n, k

g/s

2

UreaNicotinamide

Sodium benzoateSodium salicylate

Figure 7.6 Plot of surface tension versus hydrotrope concentration for


0

1

2

3

4

5

6

0 0.5 1 1.5 2


10

2 S

pec

ific

co

ncu

cta

nce, m

ho

/cm

Urea

Nicotinamide

Sodium benzoate

Sodium salicylate

Figure 7.7 Plot of specific conductance versus hydrotrope concentration

for different hydrotropes

89

1.32

1.34

1.36

1.38

1.4

1.42

1.44

1.46

0 0.5 1 1.5 2


Refr

act

ive i

nd

ex

Urea

Nicotinamide

Sodium benzoate

Sodium salicylate

Figure 7.8 Plot of refractive index versus hydrotrope concentration for


This complex arrangement may be visualized as the formation of a

stack of hydrotrope aggregates with that of solute molecules. It can also be

visualized that such a staking arrangement of solute molecules are

sandwiched between hydrotrope aggregates one upon the other. This stacking

can be assumed as a sheet of solute molecules held captive between

hydrotrope aggregates. However such a stacking arrangement need not have

any geometric restrictions, that is to say that no regular pattern of stacking can

be stressed upon.

Further increase in the solubilizing effect of hydrotrope beyond

maximum hydrotrope concentration Cmax has been hampered because

hydrotrope molecules are handicapped with the non-availability of water

molecules to form aggregates. This explains the saturation of the solubilizing

90

effect of hydrotropes beyond Cmax, which can be observed from the

experimental data.

It appears that the solute molecules after finding their way through

the interface of hydrotrope aggregates are held hidden in the hydrotropic

stack.

Though, by nature, the solute and aqueous layers are immiscible

because of difference in polarity, the hydrotrope aggregates are able to hold

them within the possible hydrotropic stack, because of different solution

properties acquired by them. Such a situation is not visible to the naked eye

probably due to the negligible difference in the surface tension and other

allied properties of the hydrotropic stack which contains the hidden solute and

aqueous phase.

However, this arrangement seems to be a purely temporary one,

because the solute particles contained within the hydrotrope stack can be

brought out by simple dilution with distilled water, which alters the solution

properties of hydrotrope stack. This causes the dissociation of hydrotrope

molecules and the properties of hydrotrope solutions with decrease in

hydrotrope concentration approach to that of water, similar to the situation

below MHC.

In general, the sort of host-guest interaction between the hydrotrope

aggregates and solute molecules seems to contribute significantly to the

overall stability of the solute-hydrotrope system.

91

7.6.2 Microscopic Studies

The SEM images of the dried solubilized product of benzoic acid in

water and aqueous sodium salicylate solution are shown in Figure 7.9 and

7.10 respectively. From Figure 7.9 it was observed that the shape of benzoic

acid crystals were needle like structure with sharp edges with irregular

pattern. On the other hand, Figure 7.10 shows that the particles of dried

solubilized form of benzoic acid in aqueous sodium salicylate solution were

reduced to sphere like structure with uniform clusters. This may be attributed

to the formation of the aggregates of sodium salicylate along with benzoic

acid.

Figure 7.9 SEM images of solubilized form of benzoic acid in water

92

Figure 7.10 SEM images of solubilized form of benzoic acid in aqueous

sodium salicylate solution

7.7 SOLUBILITY PREDICTION OF ORGANIC SOLUTES

USING ARTIFICIAL NEURAL NETWORK

The solubility of organic acid such as benzoic acid, p-hydroxy

benzoic acid, p-nitrobenzoic acid, cinnamic acid and alizarin in the presence

of various hydrotropes at different system temperatures were taken from

solubility determination part. physio-chemical properties of the organic acids

and alizarin are computed by using Chemsketch software. The physio-

chemical properties of organic solutes, temperature and concentration of

hydrotrope solutions data are used as input variables and the solubility data of

organic acids and alizarin in hydrotropes solutions are used as output

variables for an ANN model.

All solubility data of organic acids and alizarin were employed to

train, predict and validate the ANN model. The available data are randomly

93

divided into three groups. The first group is used for the process of network

training which represents 70% of the total solubility data. The second 15% of

the data is used to validate the model. The reliability of the ANN for

estimating the solubility of organic acids and alizarin in aqueous hydrotrope

solution was tested using the remaining 15%.

A feed-forward back-propagating ANN structure was used to

develop to predict the solubility of acids and alizarin in various hydrotropes

solution. ANN model is trained several times using training data. The error

between the predicted and actual solubility at different iterations were

recorded each time. The minimum means square error between the predicted

and experimental values that is reached at the optimum number of iterations is

shown in Figure 7.11.

Figure 7.11 Plot of error and number of iterations

94

One hidden layer is sufficient to approximate any continuous

nonlinear function, although more complex networks may be employed in

special applications. However, still there is no established theory to indicate

how many hidden units are needed to approximate any given function. In this

ANN model, one hidden layer with three neurons gives the best prediction

result for the given solubility data (Figure 7.12).

Figure 7.12 Schematic of the architecture of ANN used in this study

The overall MSE for all the solubility data was predicted to be

3.22×10-4

. The MSE for training, validating and testing data was 2.92×10-4

,

2.65×10-4

and 5.22×10-4

respectively. The performance of the ANN model

was evaluated by plotting the experimental vs. predicted solubility values for

training, testing and validation sets. Figures 7.13 to 7.15 display the solubility

of experimental and predicted values. The R2 values for training, validating

and testing data obtained from regression fit were 0.991, 0.992 and 0.994

respectively. This shows a better performance of the present ANN model for

the prediction of solubility of organic acids and alizarin in hydrotrope

solutions.

95

Figure 7.13 Comparison of experimental and predicted values for the

train data


validation data

96


test data

The ANN model fits the experimental data very well. The

agreement between experimental data and predicted results by ANN approach

indicate that it can be used as a powerful method for predicting the solubility

of organic solutes.

7.8 EXTRACTION OF MANGIFERIN FROM MANGO LEAVES

7.8.1 Effect of Hydrotrope on Extraction of Mangiferin

Two hydrotropes such as sodium salicylate (aromatic carboxylate)

and sodium cumene sulfonate (alkyl benzene sulfonate) were selected for the

extraction studies. The solubilization capacity of a hydrotrope is governed by

hydrophobic functionality. The hydrophobicity of the aromatic sulfonates

increases with increasing alkyl group length and they display an increasing

tendency for the solubilization of non-polar molecules. Among various

97

aromatic sulfonates, sodium cumene sulfonate has isopropyl group with three

carbons present as the side chain. However the structure of mangiferin being

phenolic would be dissolved well by aromatic hyrotropes. Sodium salicylate

is another hydrotrope selected for this extraction study which is widely used

in pharmaceutical formulations to dissolve insoluble drugs. It consists of no

side chains but the hydroxyl group in ortho position probably supports the

aggregation process.

7.8.2 Recovery of Mangiferin

The unique advantage of this hydrotropic extraction is the easy

recovery of mangiferin by diluting extract below MHC of sodium salicylate.

In case of sodium cumene sulfonate dilution of extract using water below

MHC did not provide precipitate even after 24 hours. It is mainly because of

greater affinity of sodium cumene sulfonate towards mangiferin than sodium

salicylate. Dandekar and Gaikar (2003) also reported a greater affinity of

alkyl benzene sulfonates towards curcuminoids in their study. Hence sodium

salicylate is chosen as hydrotrope for studying the effect of various factors

affecting the extraction of mangiferin from mango leaves.

7.8.3 Effect of Sodium Salicylate Concentration on Extraction of

Mangiferin

Sodium salicylate will exhibit hydrotropic action only when its

concentration is above MHC which is reported to be in the range from 0.40 to

0.50mol/L. However, being a relatively weak hydrotrope it required much

higher concentrations to give an appreciable extraction of mangiferin. But

increasing concentration of sodium salicylate above 2.0 mol/L did not give

effective results since the solution becomes more viscous and penetration of

solution through cell membrane is very difficult. The yield of mangiferin is

98

also not appreciable beyond 2.0 mol/L of sodium salicylate solution. Hence

sodium salicylate concentration of 1.0 and 2.0 mol/L were selected as lower

and upper levels for use in Response Surface Methodology (RSM)

optimization.

7.8.4 Effect of Extraction Time on Extraction of Mangiferin

Extraction time was another main parameter in the extraction

procedure. The extraction time can either be as short as few minutes or very

long up to 24 hours. In this study, the range of extraction time was designed

based on the practical and economical aspects. Extractions were conducted at

2M concentration of hydrotrope solutions at 30oC and 5% raw material

loading. Samples from the extraction vessel were withdrawn every hour and

mangiferin concentration was quantified using HPLC.

Initially the rate of extraction of mangiferin in sodium salicylate and

sodium cumene sulfonate solution was not same, which is mainly due to

difference in penetration rates through raw material cell structure. Figure 7.10

shows that the extraction of mangiferin increases with increase in extraction

time up to 6 hrs and beyond which there is no further increase in extraction of

mangiferin for both the hydrotropes. In the case of sodium cumene sulfonate

as hydrotrope the recovery of mangiferin from hydrotrope solution was not

possible by dilution with distilled water. Moreover the extraction of

mangiferin using sodium cumene sulfonate is not much significant when

compared to that of sodium salicylate. Hence sodium salicylate is used for

further experimentations.

99

0

0.5

1

1.5

2

2.5

0 2 4 6 8 10

Extraction Time (h)

Yie

ld (m

g/g

)

Na-S

Na-CuS

Figure 7.16 Extraction of mangiferin using sodium salicylate at different

time

7.8.5 Effect of Temperature on Extraction of Mangiferin

The selection of an operating range of extraction temperature

assumes significance in the extraction of bioactive compound from natural

sources. Usually extraction of organic solute increases with increase in

temperature. However, it may be indicated that increasing the temperature

beyond certain values may promote possible concurrent decomposition of

organic compounds or even the breakdown of solutes that still remained

within the plant matrix. Besides, high temperature may lead to solvent loss

through vaporization during extraction process. Therefore, moderate

extraction temperature of 30 and 50oC were chosen as the lower and upper

levels to be applied in RSM optimization.

100

7.8.6 Response Surface Methodology (RSM)

The Response Surface Methodology (RSM) has been used to study

the relation between yield of mangiferin and extraction variables such as

concentration of sodium salicylate (X1), system temperature (X2) and raw

material loading (X3). Table 7.27 gives the extraction parameters and the

operating ranges covered.

A Central Composite Design (CCD) for three factors with replicates

at the centre point was developed. The CCD contains a total of 20

experimental trials that include 8 trials for factorial design, 6 trials for axial

points and 6 trials for replications of the central points. CCD design along

with the yield of mangiferin (Y) in each trials were reported in Table 7.28

Table 7.27 The level and range of variables for extraction of mangiferin

Independent Variables

Coded levels

-1 0 1

Concentration of sodium

salicylate (mol/L)1 1.5 2

Temperature (oC) 30 40 50

Loading (%) 1 3 5

101

Table 7.28 Experimental design and yield of mangiferin extracted using

sodium salicylate solution

RunConcentration,

mol/L

Temperature,oC

Loading,

%

Mangiferin

yield, mg/g

1 1.5 40 1 2.975

2 1.5 40 5 3.584

3 1.0 30 5 1.937

4 1.0 50 5 2.259

5 1.5 40 3 6.536

6 1.5 30 3 4.680

7 1.0 50 1 1.184

8 1.5 40 3 6.556

9 1.5 50 3 5.150

10 2.0 40 3 7.209

11 2.0 30 1 1.433

12 2.0 30 5 2.390

13 1.0 30 1 0.573

14 1.5 40 3 6.438

15 1.5 40 3 6.472

16 1.5 40 3 6.528

17 1.0 40 3 5.286

18 1.5 40 3 6.732

19 2.0 50 5 2.154

20 2.0 50 1 1.470

102

The mathematical model representing the yield of mangiferin as a

function of the independent variables within the region under investigation is

expressed by the following equation

Y = 6.498 + 0.342 X1 + 0.120X2 + 0.469X3 - 0.180X12 – 1.512X2

2

- 3.148X32

-0.142X1X2 - 0.099X1X3 - 0.070X2X3 (7.5)

The prediction of mangiferin yield using the equation 7.5 has been

compared with the experimental values given in Table 7.28 and shown in

Figure 7.17. It can be ascertained from the figure that the model equation

predictions satisfactorily match the experimental values.

The significance of the regression coefficients were analyzed using

p test and t test. The p values are used to check the consequences of

interactions among the variables. In general, the larger the magnitude of the t-

va1ue and smaller the p-value, the greater is the significance of the

corresponding coefficient term. The results of statistical analysis consists of

the regression coefficient, t and p values for linear, quadratic and combined

effects of the variables were given in the Table 7.29. It can be observed from

Table 7.29 that the coefficient for the linear effect of concentration of sodium

salicylate (p = 0.010) and raw material loading (p = 0.001) are significant

compared to the effect of temperature (p = 0.2897). The quadratic effect of

temperature and raw material loading (p = 0.000) are significant compared to

the quadratic effect of sodium salicylate concentration (p = 0.402). Finally the

coefficients of the interaction terms are the least influential terms in the model

(p > 0.05).

103

0

1

2

3

4

5

6

7

8

0 1 2 3 4 5 6 7 8

Experimental values

Pre

dic

ted

va

lues

Figure 7.17 Comparison of experimental and predicted values for

mangiferin yield

Table 7.29 Estimated regression equation coefficients for mangiferin

yield

Term CoefficientsSE

Coefficientst- value p- value

Constant 6.497 0.117 55.542 0.000

X1 0.342 0.108 3.176 0.010

X2 0.120 0.108 1.119 0.289

X3 0.469 0.108 4.358 0.001

X12

-0.180 0.205 -0.876 0.402

X22

-1.512 0.205 -7.370 0.000

X32

-3.148 0.205 -15.340 0.000

X1X2 -0.142 0.120 -1.176 0.267

X1X3 -0.099 0.120 -0.829 0.426

X2X3 -0.070 0.120 -0.584 0.572

104

The Analysis Of Variance (ANOVA) to determine the statistical

significance of the model equation was evaluated and the results are presented

in Table 7.30. The ANOVA of the regression model showed that the model is

statistically significant (p = 0.000). The linear and quadratic term in the model

were highly significant (p<0.05) and adequate to represent the relationship

between mangiferin yield and sodium salicylate concentration, system

temperature and raw material loading. The model adequacies were checked by

R2 and adjusted R

2. A higher value of R

2 (0.988) shows that the predicted

model suit the experimental behavior of the system. In addition, the value of

adjusted R2 (0.978) was also very high to support for a high significance of

the model.

Table 7.30 Analysis of variance (ANOVA) for the quadratic model

SourceDegree of

Freedom

Sum of

squares

Mean

squaresF -value p-value

Model 9 98.508 10.945 94.53 0.000

Linear 3 3.511 1.170 10.11 0.002

Quadratic 3 94.717 31.573 272.69 0.000

Interaction 3 0.297 0.093 0.80 0.520

Residual error 10 1.158 0.116

Lack of Fit 5 1.106 0.221 21.17 0.002

Pure error 5 0.052 0.010

Total 19 99.665

7.7.7 Analysis of response surface plot

The response surface plots (Figure 7.18-7.20) illustrate the

interactive effects of the extraction variables on mangiferin yield. Figure 7.18

105

shows the effects of sodium salicylate concentration and extraction

temperature on mangiferin yield, while the other variable raw material

loading is maintained constant at its middle level (3%). It can be ascertain

from Figure 7.18 that the mangiferin yield increases with increase in sodium

salicylate concentration where as for extraction temperature, mangiferin yield

increases only up to 40oC approximately. At higher value of extraction

temperature (above 40oC) mangiferin yield decreases.

Figure 7.18 Effect of sodium salicylate concentration and temperature

on mangiferin yield

Figure 7.19 Effect of sodium salicylate concentration and raw material

loading on mangiferin yield

106

Figure 7.19 shows the effects of sodium salicylate concentration and

raw material loading on mangiferin yield, while the system temperature is

kept constant at its middle level (40oC). It has been observed that the effect of

sodium salicylate concentration on the mangiferin yield was same as shown in

the Figure 7.18. When the raw material loading is increased, maximum yield

of mangiferin obtained approximately at 3%. Lower or higher than 3% raw

material loading decreases the mangiferin yield.

Figure 7.20 Effect of temperature and raw material loading on

mangiferin yield

Figure 7.20 shows the interaction effect of system temperature and

raw material loading on mangiferin yield while sodium salicylate

concentration is kept constant at its middle level (1.50 mol/L). It was

observed that the extraction temperature and raw material loading have

similar effect on mangiferin yield. The yield of mangiferin increases upto its

middle level value of both, system temperature and raw material loading

(40oC and 3%). Beyond these values the mangiferin yield starts to decrease.

It is evident from the response surface plots that the higher sodium

salicylate concentration (2.0mol/L) and middle value of extraction

temperature and raw material loading (40oC & 3%) gives maximum yield of

mangiferin.

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