A Solubility Study of the Boric Acid-Water-Sorbitol
System at Various Temperatures*
By JOHN J. SCIARRA,t JOHN AUTIANJ and NOEL E. FOSSg
A study of the effect of various concentrations
of sorbitol and temperature on the solubility
andaheatof solution of boric acid in water has
been made. This system was studied at
temperatures of 2 1 O . 2 S 0 , 30°, 40°, SO’, and
60 O. Concentrations of sorbitol ranging
from 0 to 7 0 per cent by weight sorbitollin
increments of 5 per cent were utilized in this
study. The results of these experiments
showed !the relationship between (1) solu-
bility of boric acid and (2) temperature and
concentration of sorbitol. A phase dia-
grap of the boric acid-water-sorbitol system
is given. The heat of solution for the various
systems was calculated. The specific gravity
of all solutions was determined by the pycno-
metric method.
ORIC ACID is soluble to the extent of about 5%
by volume in water or 1 : 1 8 at 25O ( 1 ) .
This limited solubility of boric acid in aqueous
solution has prompted many workers to investi-
gate the effect of various solvents and other sub-
stances on the solubility of boric acid (2-5). A
recent paper by Sciarra, Autian, and Foss re-
ported that a 70% by weight sorbitol solution
increased the solubility of boric acid from the
above to l8.66yOby weight or 1:3.45 at 25’ ( 6 ) .
This represented a significant increase in the
solubility of boric acid and seems worthy of
further study; therefore, an investigation dealing
with the solubility of boric acid in various con-
centrations of sorbitol and at various tempera-
tures was made. From the data, the heat of sol-
ution of boric acid was evaluated and the appli-
cation of the van’t Hoff equation to this system
was studied.
Boric acid reacts with sorbitol in solution to
form a boric acid-sorbitol complex. Upon anal-
ysis of this solution, three components can be
detected: boric acid, water, and sorbitol. This
multicomponent system can be represented
graphically by means of a phase diagram and
* Received April, 1957, from the Pharmaceutical Research
Laboratory, University of Maryland, School of Pharmacy,
Baltimore.
Presented to the Scientific Section, A. PH. A,, New York
meeting, April 1957.
Abstracted in part from a dissertation submitted to the
Graduate School of the University of Maryland by John J.
Sciarra in partial fulfillment of the requirements for the de-
gree of Doctor of Philosophy, June 1957.
Adapted from the manuscript submitted by John J. Sci-
arra which received honorable mention in the 1957 Lunsford
Richardson Pharmacy Awards competition.
t Present address: Assistant Professor of Pharmaceutical
Chemistry, St. John’s University, College of Pharmacy,
Brooklyn, N. Y.
Present address: Assistant Professor of Pharmacy,
University of Michigan, College of Pharmacy, Ann Arbor.
0 Dean and Professor of Pharmacy.
144
plotted on triangular graph paper. This diagram
is useful for this system since the amount of sor-
bitol needed to dissolve a given amount of boric
acid can readily be ascertained from the phase
diagram.
Temperature is an important consideration
when determining solubility. Generally, heat
is absorbed when salts dissolve and, accordingly,
they are more soluble a t higher temperatures
(7).
The solubility of a solid is a special case of an
equilibrium constant (8). The relation between
an equilibrium constant and the absolute temp-
erature was developed by van’t Hoff. An equi-
librium constant enables one to predict how far a
chemical reaction will go; it can be calculated
for any temperature when it is known a t two
temperatures.
The mathematical relation is: (dln S/dt) =
( A H / R T * )and, when integrated,
log S = (-AH/2.303R X 1/T + constant), or,
log &/SI = [AH(Tz - T I )]/[2.303R(TzTI)1
where Szand .Sl are the solubilities, in moles per
1000 Gm. of solvent, at the absolute tempera-
tures Tz and T I ; R is the gas constant; and A H
is the heat of solution in calories per degree per
mole. In this integration AH is assumed to be
constant, an assumption that is not entirely justi-
fied (8).
If a plot of the log S vs. 1/T yields a straight
line, the slope of the line becomes equal to
-AH/2.303R. From this A H can readily be
calculated.
EXPERIMENTAL.
Solutions containing 0% sorbitol to 70y0sorbitol
by weight were prepared by diluting Sorbom solu-
tion,’ with the necessary amount of water. Each
of these solutions was neutralized to phenolphthalein
by adding a few drops of sodium hydroxide solution
to produce a faint pink color. The solution was
then placed in contact with an excess of finely di-
vided crystalline boric acid, U. S. p., in a solubility
tube. The solubility tube was then placed in the
thermostat and stirred constantly for twenty-four
hours. After stopping the stirring motor and allow-
ing the undissolved particles to settle to the bottom,
2 25-ml. portions of the clear supernatant liquid were
removed, placed into tared beakers, and quickly
Seventy per cent sorbitol. Atlas Powder Co..Wilmiugton,
Del.
February 1958 SCIENTIFIC EDITION 145
weighed. The amount of boric acid in these solu- 30
tions was determined by assaying the solution ac-
cording to the U. S. P. assay for boric acid (1).
A t the same time, a 25-1111. Gay-Lussac specific
gravity bottle was filled with the saturated solution
25
of boric acid in the sorbitol solvent and the specific
gravity determined by the pycnometric method (9).
The specific gravity of the sorbitol solvent alone was
0
also determined. Y
The solubility of boric acid and specific gravity of 020
each of the above solutions were determined at
21'. 25', 30°, N o ,50°, and at 60" f 0.1'.
8m
t-
RESULTS I
52 15
W
The results of the above experiments were treated z
in several different ways in order to best show the t-
relationship existing among the various solutions. z
Tables I and I1 give the specificgravity of sorbitol 10
solutions and of saturated boric acid solutions in a
sorbitol a t various temperatures as determined by W
0
the pycnometric method. Specific gravity of a solu-
tion of boric acid in sorbitol solution vs. per cent 5
weight sorbitol a t 21' and 60" was plotted and is
shown in Fig. 1.
Table I11 gives the solubility of boric acid in
sorbitol solutionsa t various temperatures. Figure 2
shows the solubility of boric acid in sorbitol solutions 0
0 30 40 50 60
at various temperatures while Fig. 3 shows the solu- TEMPERATURE * C.
bility of boric acid a t various concentrations of Fig. 2.-Effect of temperature upon the solubility
sorbitol. of boric acid in sorbitol solution. A-zero, B-10,
C-20, D-30, E 4 , F-50, G 4 0 , H-70,
per cent weight sorbitol.
I .30

- 600C
2s
500 c
40°C
30°C
I .25 25°C
21°C

if+ 1.20
3
J
0
VI
c
0 'C! $0 3!! ab 5 I0 I
60 JO
*
8;
PER C E N T *LIGHT SORBlTOL
c_ 1.15 Fig. 3.-Isotherm curves showing solubility of
aa boric acid in sorbitol solution.
a The composition of various solutions consisting

;
0

Q
1.10
of boric acid, sorbitol and water is given in Table IV.
The results a t 25O, 40°, and 60' were plotted on tri-
angular graph paper and are shown in Fig. 4.
v) Figure 5 shows the relationship between the log
of boric acid solubility in moles per 1000 Gm. of
solvent and reciprical of absolute temperature.
From this graph the slope was determined from
I .a which A H was calculated. Then, by substituting
these values of AH in van't Hoff's equation the
solubility of boric acid was calculated a t 35' and
compared with the value obtained from Fig. 2.
These results are shown in Table V.
I .oc
20 40 60 00 DISCUSSION
PER CENT WEIGHT SORBITOL
Fig. 1.-Isotherm curves showing specific gravity The specific gravity of sorbitol solutions was
of saturated solution of boric acid in sorbitol. found to increase with an increase in concentration
146 JOURNAL
OF THE PHARMACEUTICAL
AMERICAN ASSOCIATION Vol. XLVII, No. 2

TABLEI.-SPECIFICGRAVITYOF SOR~ITOL
SOLUTIONS
AT VARIOUSTEMPERATURES

Concn. of
of Sorbitol,
% w/w
c
210 25
Specific Gravity
30° 40 50" 60
-
0 1.ooo 1.000 1.000 1 .oon 1.000 1.000
5 1.019 1.018 1.018 1.017 1.017 1.017
10 1.037 1.034 1.036 1.036 1.036 1.035
15 1.056 1.055 1.054 1.054 1.053 1.054
20 1.075 1.074 1.075 1.074 1.074 1.073
25 1.096 1.095 1.095 1.094 1.093 1.093
30 1.118 1.116 1.115 1.115 1.115 1.114
35 1.137 1.137 1.135 1.134 1.133 1.133
40 1.151 1.150 1.150 1.148 1.147 1.157
45 1.181 1.178 1.179 1.177 1.176 1.179
50 1.202 1.200 1.200 1.198 1.195 1.200
~ ~.
55 1.227 1.225 1.226 1.224 1.224 1.226
60 1.250 1.249 1.248 1.247 1.244 1.251
65 1.275 1.273 1.274 1.272 1.271 1.279
70 1.298 1.298 1.289 1.297 1.295 1.291

TABLE OF SATURATED
II.-SPECIF~CGRAVITY SOLUTION
OF BORICACIDI N SORBITOL
SOLUTION
AT VARIOUS
TEMPERATURES
Concn. of
Sorbitol, 7 Specific Gravity
% w/w 210 25 30" 40 50' 60
0 1.018 1.020 1.023 1.029 1.036 1.046
5 1.036 1.038 1.041 1.047 1.053 1.061
10 1.056 1.056 1.059 1.064 1.071 1.079
15 1.074 1.075 1.077 1.082 1.084 1.096
20 1.095 1.095 1.096 I .i n 1 1.108 1.114
25 1.113 1.114 1.116 1.120 1.124 1.131
30 1.134 1.134 1.140 1.140 1.145 1.150
35 1.152 1.152 1.154 1.157 1.163 1.167
40 1.165 1.164 1.166 1.170 1.171 1.187
45 1.190 1.190 1.192 1.194 1.197 1.206
50 1.211 1.210 1.210 1.210 1.214 1.221
55 1.231 1.231 1.232 1.234 1.235 1.240
60 1.253 1.252 1.252 1.254 1.257 1.258
65 1.274 1.272 1.272 1.271 1.273 1.272
70 1.294 1.292 1.293 1.291 1.290 1.294

TABLE SOLUTION
III.--SOLUBILITYOF BORICACIDIN SORBITOL AT VARIOUS
TEMPERATURES
Concn. of Solubility
Sorbitol, 210 25' 30' 40 i0 60"
% w/w A' Bb A B A B A B A B A B
0 18.88 5.03 16.98 5.57 14.73 6.36 11.36 8.09 9.03 9.98 6.91 12.65
5 16.13 5.74 14.60 6.31 12.65 7.21 10.01 8.95 8.01 10.95 6.33 13.46
10 13.45 6.70 12.68 7.09 11.12 7.99 8.91 9.78 7.25 11.76 5.82 14.25
15 11.98 7.33 11.10 7.87 9.87 8.76 7.97 10.64 6.45 12.84 5.38 ~.
1.5.00 ~~

10.19 8.37 9.75 8.72 8.74 9.63 7.13 11.55 5.93 13.56 4.90 16.00
9.14 9.09 8.73 9.47 7.83 10.45 6.42 12.46 5.43 14.43 4.51 16.88
8.17 9.88 7.71 10.42 7.04 11.31 5.93 13.14 4.98 15.26 4.15 17.80
7.36 10.68 7.00 11.18 6.40 12.11 5.41 14.02 4.53 16.33 3.87 18.60
40 6.88 11.22 6.62 11.63 6.01 12.64 5.12 14.53 4.36 16.69 3.56 19.57
46
__ 6.19 12.03 5.72 12.92 5.28 13.86 4.52 15.83 3.88 17.97 3.28 20.52
50 5.63 12.87 5.20 13.80 4.134 14.72 4.17 16.67 3.59 18.94 3.00 21.76
55 5.01 13.99 4.64 14.98 4.32 15.89 3.76 17.87 3.26 20.02 2.80 22.60
60 4.44 15.28 4.15 16.17 3.91 17.02 3.44 18.91 2.97 21.31 2.45 24.63
65 3.98 16.45 3.75 17.31 3.50 18.32 3.10 20.27 2.75 22.30 2.41 24.48
70 3.66 17.43 3.37 18.66 3.19 19.47 2.41 24.20 2.48 23.74 2.25 25.65
'I A -Solut,hty of boric acid expressed as rnl of w l \ ent, Gm of d u t e
b B-Solubility of boric acid expressed as per cent by weight.

of sorbitol and decrease with a n increase in tempera-
ture. The specific gravity of the various solutions
varied from 1.000 for pure water (0% sorbitol) to
1.291 for a 70% solution of sorbitol at 60". As
shown in Fig. 1, the relationship existing between
specific gravity of a saturated solution of boric acid
in sorbitol solution and concentration of sorbitol is a
linear function. While the specific gravity of
sorbitol solution was found t o decrease with a n
increase in temperature, the reverse is true for the
saturated solution of boric acid in sorbitol solution.
The specific gravity of saturated solutions of boric
acid in sorbitol solution was found t o increase with
an increase in temperature. This is attributed to the
increase in concentration of boric acid brought about
by the increase in temperature.
February 1958 SCIENTIFIC
EDITION 147

IV.-COMPOSITION
TABLE OF BORICACID-WATER-SORBITOL
SYSTEM
AT VARIOUSTEMPERATURES

Boric Acid, Sorbitol, Water, Boric Acid,

Composition
Sorbitol. Water, Boric Acid, Sorbitol, Water,
-
% % % % % % % % %
-
7 -210- 7
- -250- -7 - 30°
5.03 0.00 94.97 5.57 0 .oo 94.43 6.36 0.00 93.64
5.74 4.76 89.50 6.31 4.68
-. . _ 89.01
_.. .~ 7.21 4.64 88.15
6.70 9.33 83.97 7.09 9.29 83.62 7.99 9.20 82.81
7.33 13.90 78.77 7.87 13.82 78.31 8.76 13.69 77.55
8.37 18.33 73.30 8.72 18.26 73.02 9.63 18.07 72.30
9.09 22.73 68.18 9.47 22.63 67.90 10.45 22.39 67.19
9.88 27.04 63.08 10.42 26.87 62.71 11.31 26.61 62.08
10.68 31.26 58.06 11.18 31.09 57.73 12.11 30.76 57.13
ii.22 35.51 53.27 11.63 35.47 52.90 12.64 34.94 52.42
12.03 39.59 48.38 12.92 39.19 47.89 13.86 38.76 47.38
12.87 43.57 43.56 13.80 43.10 43.10 14.72 42.64 42.64
13.99 47.31 38.70 14.98 46.76 38.26 15.89 46.26 37.85
15.28 50.83 33.99 16.17 50.30 33.53 17.02 49.79 33.19
16.45 54.31 29.24 17.31 53.75 28.94 18.32 53.09 28.59
17.43

8.09
57.80
40°-
0.00
24.77

91.91
- -- 18.66

9.98
56.96
-50'-
0.00
24.38
-7

90.02
~~
19.47

12.65
56.37
-60'
0.00 87.35
-
24.16

8.95 4.55 86.50 10.95 4.45 84.60 13.46 4.33 82.21

9.78 9.02 81.20 11.76 8.82 79.42 14.25 8
- .5
_ _8 77.17
..
10.64 13.40
_. 75.96 12.84 13.07 74.09 15.00 12.75 72.75
11.55 17.69 70.76 13.56 17.29 65.15 16.00 16.80 67.20
12.46 21.89 65.65 14.43 21.39 64.18 16.88 20.78 62.34
13.14 26.06 60.80 15.26 25.42 59.32 17.80 24.66 57.54
14.02 30.07 55.91 16.33 29.28 54.39 18.60 28.84 52.56
14.53 34.19 51.28 16.69 33.34
~. .~ 49.97 19.57 32.57 47.86
15.83 37.88 46.29 17.97 36.91 45.12 20.52 35.77 43.71
16.67 41.67 41.66 18.94 40.53 40.53 21.76 39.13 39.11
17.87 45.17 36.96 20.02 43.99 35.99 22.60 41.47 35.93
18.91 48.65 32.44 21.31 47.21 31.48 24.63 45.22 30.15
20.27 51.82 27.91 22.30 50.51 27.19 24.48 49.09 26.43
24.20 52.96 22.84 23.74 53.38 22.88 25.65 52.05 22.30

The solubility of boric acid in sorbitol solutions
was found to increase with an increase in tempera-
ture and concentration of sorbitol. The solubility
of boric acid varied from 5.0370 in water at 21" to
25.7y0 in 70% sorbitol solution at 60". Figures 2
and 3 can be used to determine the solubility of boric
acid in sorbitol solutions of 0 to 70% by weight a t
temperatures ranging from 21' t o 60'. This rela-
tionship is important when one considers problems of
formulation, stability, and storage where slight
changes in temperature may seriously affect the
solubility.
in a lesser solubility of boric acid. Since both the
boric acid and sorbitol will be competing for the
lesser amount of water present, the sorbitol, having
the greater solubility, will dissolve a t the expense of
the boric acid. This phenomenon is further shown
on the phase diagram, since the curves must ap-
proach the point representing 1 0 0 ~ o sorbitol, 0%
water, and 0% boric acid, which is located at the
apex of the triangle. As can be seen from the curves
the increase in temperature lowers the curves, in-
creasing the area above the curve resulting in a

The composition of each of the solutions, in per

cent by weight of sorbitol, boric acid, and water,
was plotted on triangular graph paper. The
maximum concentration of boric acid was at 60"
and found t o be 25.7y0 at a concentration of 52.1yc
sorbitol and 22.2% water. At higher concentrations
one or more of the components precipitated. A
phase diagram is very useful in determining concen-
trations when one or two components are h e d
at a definite value. For example, a t 25", in order to
dissolve 8% boric acid, 14% of sorbitol and 78% of
water is required. This solution will be saturated
with boric acid at this temperature. The area above
the curves in Fig. 4 represents concentrations of the
three components which will yield a clear solution.
One or more components will precipitate in the area
beneath the curves. Theoretically, a maximum
solubility is reached at about 50 to 60% sorbitol
(depending upon temperature) and it is believed that Fig. &Phase diagram of boric acid-water-sorbitol
higher concentrations of sorbitol will actually result system.
148 JOURNAL OF THE AMERICAN ASSOCIATION Vol. XLVII. No. 2
PHARMACEUTICAL

greater area of solubility for boric acid in the sorbitol lation of AH for each of the solvents ranging froni
solvent. water (0% sorbitol) t o 70% sorbitol, shows that
Figure 5 shows the log of solubility PIS.reciprocal of AH decreases with an increase in concentration of
absolute temperature. This plot yielded a straight sorbitol. This change indicates that less heat is
line from which the slope was determined. Calcu- involved when a mole of boric acid dissolves in 70a/o
sorbitol as compared t o dissolving in water or in a
TABLE V.-COMPARISON OF CALCULATED lesser concentration of sorbitol. The application of
SOLUBILITY WITH EXPERIMENTALLY DETERMINED van’t Hoff’s equation to this system was tested and
SOLUBILITY OF BORICACID found to give acceptable results as shown in Table V.
Utilizing this equation, the solubility of boric acid
A B C D E can be calculated a t any temperature. This con-
0 5.030 1.223 1.257 1.236 stant variant is important in pharmaceutical for-
5 4.580 1.405 1.399 1.406 mulations since a knowledge of solubility enters
10 4.260 1.560 1.558 1.551 into many problems.
15 4.030 1.755 1.723 1.699
20 3.840 1.895 1.907 1.897
25 3.470 2.082 2.058 2.081 SUMMARY AND CONCLUSIONS
__
3n - ___
2.420 ~ 2.247
~~ 2.269
~ ~. 2.268
35 3.200 2.475 2.426 2.416
40 3.200 2.541 2.537 2.556 1. A solubility study of the boric acid-water-
45 3.200 2.779 2.860 2.798 sorbitol system has been made a t various temp-
50 3.050 2.997 3.060 2.989 eratures.
55 2.900 3.249 3.340 3.254
60 2.750 3.556 3.576 3.550 2. The specific gravity of sorbitol solutions
65 2.470 3.848 3.875 3.792 was determined b y the pycnometric method and
70 2.410 4.193 4.245 4.144
found t o increase with a n increase in conceritra-
A-Concentration of sorbitol, per cent by weight. B-AH tion of sorbitol, a n d decrease with a n increase in
calculated from slope, calories/mole/degree. C-Calculated
solubility at 35O when TI = 323O K.,moles/1000 Gm. sol- temperature. While the specific gravity of sor-
vent. D-Calculated solubility at 35’ when TI = 298” K . .
moles/1000 Gm. solvent. E-Solubility determined experi- bitol solution was found t o decrease with a n in-
mentally from Fig. 2, moIes/1000 Gm. solvent.
crease in temperature, the reverse was found to
be true for the saturated solution of boric acid in

o.80r sorbitol solution. This was due t o the in-

creased solubility of boric acid at elevated tem-
pera tures.
3. T h e solubility of boric acid in sorbitol sol-
ution was determined at various temperatures
and concentrations of sorbitol a n d found t o in-
crease with a n increase in temperature and con-
centration of sorbitol.
1. A phase diagram of the boric acid-water-
sorbitol system was determined at various
temperatures. The heat of solution, hH, for the
various systems was evaluated b y plotting log of
solubility of boric acid versus reciprocal of ab-
solute temperature. It was found t h a t AH de-
creased with a n increase in concentration of sor-
bitol. T h e application of van’t Hoff’s equation
t o this system was tested and found to give ac-
ceptable results.

REFERENCES
(1) “Pharmacopeia of the United States of America,’.
15th Rev., Mack Printing Company, Easton, Pa., 1955, p. 103.
(2) Holm Phavm. Weekblod, 58, 860(1921) ; through
Chem. Absf;. 15. 2962(1921).
(3). Miner,’C. S., and Dalton, N. N., “Glycerol.” Reinhold
Publishing Co. New York 1953.
(4) Kendall.’T.. and Andrews.. -T. C... J . A m . Chem. SOC.,43.
1545(1921).
(5) Ryss, I. G.,Slutskaya, M . M..and Vitukbnovskaya.
B . S . , J . App. Chem. U.S.S.R.,25,157(1952); throughchcm.
Abslr. 48 8014(1954).
O/ (6) kcikra J. J. Autian J., and Foss. N. E., THISJOUR-
N A L , P i a c f . Eh., 18: 366(1967).
-0 90 (7) Daniels F. and Alberty R . “Physical Chemistry,”
3.0 3.1 3.2 33 3 4 John Wiley &’Son’s. Inc. New Gork,’ 1955. p. 277.
I I T X1C-30K (8) Daniels, F., Math&, J. H . , and Williams, J . W., el al..
“Exper-ental Physical Chemistry,” 4th ed., McGraw-Hill
Fig. 5--Plot of log solubility of boric acid ys, BooE Co., Inc., New York, 1949. p. 125.
reciprocal of absolute temperature (9) I b i d . , pp. 101, 427.