1668 Langmuir 2000, 16, 1668-1674

Effect of pH on Mandelic Acid Diffusion in Water in Oil

Highly Concentrated Emulsions (Gel-Emulsions)

G. Calderó, M. J. Garcı́a-Celma, C. Solans, and R. Pons*

Departament Tecnologia de Tensioactius, IIQAB (CSIC), C. Jordi Girona 18-26,
08034 Barcelona, Spain

Received July 20, 1999. In Final Form: October 4, 1999

Diffusion of a weak acid (mandelic acid) was studied as a function of pH in highly concentrated W/O
emulsions (gel-emulsions). The main characteristic of highly concentrated emulsions is their high internal
phase volume. Gel-emulsions were prepared using aqueous solutions at different pH values. The surfactant
was of the ethoxylated alcohol type and the oil, a hydrocarbon. Diffusion studies were performed by putting
in contact two emulsions of the same composition except for the diffusion molecule and in some experiments
the pH of the medium. The concentration of this molecule was determined as a function of the distance
to the plane of contact. Diffusion coefficients were determined by means of numerical solutions of Fick’s
laws with appropriate boundary conditions. It has been found that the pH of the medium strongly influences
diffusion. This has been attributed to the modification of the partition coefficient of mandelic acid between
the continuous and dispersed phases caused by the different solubility of the neutral and ionized species.
The results allow confirmation of the contribution of the partition coefficient to the diffusion in gel-
emulsions and an explanation of the mechanism by which diffusion takes place in these systems.

1. Introduction
Highly concentrated emulsions are dispersed systems
with the main characteristic of having a high internal
phase ratio (higher than 74 wt %).1-3 They form in water/
nonionic surfactant/oil systems in which the content in
dispersed phase can be even higher than 99% and the
surfactant content as low as 0.5 wt %.4-7 W/O highly
concentrated emulsions only form above the HLB-tem-
perature and their stability is at maximum about 20-30
°C above this temperature.4-8 The aspect of gel-emulsions
can vary from transparent to translucent or white
depending on composition and temperature variables.
Their rheological behavior is viscoelastic.2,9-10 They have
gellike consistency, and this is why highly concentrated
W/O emulsions are also known as gel-emulsions. Struc-
turally, they are foamlike materials; owing to their high
internal phase ratio, the dispersed phase droplets are Figure 1. Schematic representation of a gel-emulsion, with
dispersed aqueous phase drops and a continuous phase
closely packed and have polyhedral shapes. Another consisting of a microemulsion.
interesting structural feature of these emulsions is that
the continuous phase is a W/O microemulsion.5,11,12 At
equilibrium, gel-emulsions separate in two phases: an
* To whom correspondence should be addressed: Tel.: 34-3- aqueous phase (which composition corresponds to the
4006150. Fax: 34-3-2045904. E-mail: RPPTEN@IIQAB.CSIC.ES. dispersed phase) and a W/O microemulsion that has the
(1) Lissant, K. J. J. Colloid Interface Sci. 1966, 22, 462. same composition as the continuous phase of the gel-
(2) Princen, H. M. J. Colloid Interface Sci. 1979, 71, 55. emulsion. The presence of two kinds of water droplets,
(3) Sagitani, H.; Hattori, T.; Nabeta, K. Nippon Kagaku Kai Shi 1983, the dispersed phase droplets (with droplet sizes ranging
10, 1399.
(4) Solans, C.; Comelles, F.; Azemar, N.; Sánchez-Leal, J.; Parra, J. approximately from 0.5 to 5 µm) and the droplets of the
L. Proceedings of the XVII Jornadas CED/AID; AID: Barcelona, 1986; W/O microemulsion which constitute the continuous phase
p 109. of gel-emulsions (with mean droplet size of about 0.01
(5) Kunieda, H.; Solans, C.; Shida, N.; Parra, J. L. Colloids Surf.
1987, 24, 225. µm) (Figure 1), makes these emulsions especially inter-
(6) Solans, C.; Garcı́a-Domı́nguez, J. J.; Parra, J. L.; Heuser, J.; esting as drug delivery systems for controlled release in
Friberg, S. E. Colloid Polymer Sci. 1988, 266, 570. the pharmaceutical and cosmetic industries.13
(7) Solans, C.; Azemar, N.; Parra, J. L. Prog. Colloid Polym. Sci.
1988, 76, 224. In earlier papers we reported on the important impli-
(8) Kunieda, H.; Evans, D. F.; Solans, C.; Yoshida, M. Colloids Surf. cations of the structural features of these emulsions in
1990, 47, 35 the diffusion of molecules incorporated in the aqueous
(9) Pons, R.; Solans, C.; Stébé, M. J.; Erra, P.; Ravey, J. C. Prog. component.14-17 Diffusion of a hydrophilic molecule from
Colloid Polym. Sci. 1992, 89, 110.
(10) Pons, R.; Erra, P.; Solans, C.; Ravey, J. C.; Stébé, M. J. J. Phys.
Chem. 1993, 97, 2320. (13) Pons, R.; Calderó, G.; Garcı́a-Celma, M. J.; Azemar, N. Solans,
(11) Solans, C.; Pons, R.; Zhu, S.; Davis, H. T.; Evans, D. F.; C. In Novel Cosmetic Delivery Systems; Magdassi, S., Touitou, E., Eds.;
Nakamura, K.; Kunieda, H. Langmuir 1993, 9, 79. Marcel Dekker: New York; 1999; p 169.
(12) Pons, R.; Ravey, J. C.; Sauvage, S.; Stébé, M. J.; Erra, P.; Solans, (14) Pons, R.; Calderó, G.; Garcı́a-Celma, M. J.; Azemar, N.; Carrera,
C. Colloids Surf. 1993, 76, 171. I.; Solans, C. Prog. Colloid Polym. Sci. 1995, 100, 132-136.

10.1021/la990971w CCC: $19.00 © 2000 American Chemical Society

Published on Web 12/10/1999
pH Effect on MA Diffusion in Gel-Emulsions Langmuir, Vol. 16, No. 4, 2000 1669

Figure 2. Dissociation equilibrium of mandelic acid.

gel-emulsions to a receptor solution was studied and

related to the partition coefficient of the diffusing molecule
between the continuous and the dispersed phases of gel-
emulsions as well as the stability of the emulsions as a
function of several composition variables. Other diffusion
studies in the gel-emulsion itself as a function of tem-
perature and several composition variables were also
performed.18 The hydrophilic molecule chosen was, as in
the earlier diffusion studies, mandelic acid (MA), an alpha
hydroxyl acid suitable for UV determination. Mandelic
acid is a weak acid which dissociates in aqueous solution
giving mandelate ions. The degree of ionization depends
obviously on the pH of the medium. At basic pH the
formation of mandelate is favored while at acidic pH
values, the nonionized species predominate (Figure 2).
All the studies mentioned above were performed at the Figure 3. Experimental setup used for the diffusion experi-
same starting pH of the donor and receptor medium (5.89 ments.
in the absence of the molecule and 2.26 in the presence
of 1% of mandelic acid). In this paper, the influence of pH
in mandelic acid diffusion has been studied.

2. Experimental Section
2.1. Materials. Mandelic acid (R-hydroxyphenylacetic acid
puriss. p.a.>99%), HCl, and decane were from Fluka. NaOH
was from Merck. The tetraethylene glycol mono-n-hexadecyl ether
(C16E4) was from Nikko Chemicals Co. Ltd. (Japan). Water was
MilliQ filtered. All products were used as received.
2.2. Methods. Gel-Emulsion Preparation. Gel-emulsions were
prepared by slow addition of the internal phase to the external
phase under continuous stirring. The internal phase consisted
of water or aqueous HCl 0.1 N, HCl 0.01 N, NaOH 0.1 N, and
NaOH 0.01 N solutions. The donor gel-emulsion contained also
a 1% w/w mandelic acid. The external phase consisted of a
surfactant/oil binary mixture whose ratio was 40/60 (w/w). The
internal phase ratio was 95 wt %.
Diffusion Experiments. Diffusion of MA was studied within
the gel-emulsion itself. The experimental setup consists of a box
with a slit in the middle (Figure 3). The gel-emulsion containing
MA is placed in one of the compartments and the gel-emulsion
with the same composition except for the MA is placed in the
other compartment (Figure 3a). The experiment starts when the
slit is removed (Figure 3b). At this moment both gel-emulsions
come into contact and diffusion starts. The box is kept at a
controlled temperature for a given time (typically 15 h) and then
the system is sliced by introducing thin glass plates that
effectively stop diffusion (Figure 3c). Samples are withdrawn
from each compartment and their content in MA is measured by
UV spectrophotometry. Figure 4. Typical diffusion results. The points correspond to
Determination of Diffusion Coefficients from Experimental the experimental data and the curve to the best fit of eq 1.
Results.14-18 The concentration of MA is plotted as a function of
the distance to the middle plane of contact between the two x > 0, c d c0 and x < 0, c ) 0 and the condition of finite
starting emulsions. Typical results obtained are shown in Figure concentration at infinite distance from the contact plane is
4. The exact solution of Fick’s equation for the boundary conditions

( ( ))
c0 x
c) 1 - erf (1)
(15) Calderó, G.; Garcı́a-Celma, M. J.; Solans, C.; Plaza, M.; Pons, 2 (4Dt)1/2
R. Langmuir 1997, 13, 385.
(16) Calderó, G.; Garcı́a-Celma, M. J.; Solans, C.; Stébé, M. J.; Ravey,
J. C.; Rocca, S.; Pons, R. Langmuir 1998, 14, 1580.
The curve in Figure 4 corresponds to the best fit of eq 1. If the
(17) Rocca, S.; Garcı́a-Celma, M. J.; Calderó, G.; Pons, R.; Solans C.; diffusion time is long, eq 1 is no longer valid because the condition
Stébé M. J. Langmuir 1998, 14, 6840. of finite concentration at infinite distance is not accomplished.
(18) Calderó, G., in preparation. In this case the numerical solution of Fick’s equation has to be
1670 Langmuir, Vol. 16, No. 4, 2000 Calderó et al.

used with the boundary conditions of finite length of diffusion.14 Table 1. pH and Ionic Strength (I) of Different Solutions
Concerning the calculation of the diffusion coefficient in a system in Absence (0%) and Presence (1%w/v) of MA
with different partition coefficients, the infinite composite 0% MA 1% MA
medium solution of Fick’s equations was used.19 The concentra-
tion profile is given by aqueous solution pH I pH I
HCl 0.01 N 1.99 0.01 1.92 0.012

[ ( )]
co(D2/D1)1/2 H2O 5.89 6 × 10-7 2.26 0.003
x
c1(x,t) ) c0 + 1 - erf (2) NaOH 0.01 N 11.98 0.01 2.64 0.039
k + (D2/D1)1/2 (4D1t)1/2 NaOH 0.1 N 12.53 0.1 12.13 0.1

Table 2. Conductivity at 25 °C of the Aqueous Solutions

[ ( )]
co x used for Gel-Emulsion Preparation
c2(x,t) ) 1 + erf (3)
k + (D2/D1)1/2 (4D2t)1/2 aqueous solution 0% MA (µS/cm) 1% MA (µS/cm)
HCl 0.01 N 2970 3470
for the concentration left and right of the contacting plane. k H2O 1.2 1766
corresponds to the partition coefficient between the two media. NaOH 0.01 N 965 1537
MA Analysis. Spectrophotometric analysis was performed NaOH 0.1 N 16 010 6380
using a Shimadzu UV-265FW Spectrophotometer. MA displays
a principal absorption peak at a wavelength of 257 nm. 0.1 g of presence and absence of MA. The ionic strength (I) was
emulsion were diluted in 5 mL of ethanol and the UV intensity calculated according to the equation
at 257 nm was recorded.

MA Partition Coefficient Determination. MA partition coef-
ficients in the gel-emulsion were determined by measuring the
concentration of MA in the internal and external phases at
equilibrium. 0.1 g of the oil phase were diluted in 5 mL of ethanol
and the UV intensity at 257 nm was recorded. This high dilution
eliminates decane and surfactant interferences. MA concentra-
tion was determined by calibration. MA concentration in the
aqueous phase was determined by mass balance. Partition
coefficients (P) were calculated as the quotient18
[MA]o
P) (4)
[MA]w
Where [MA]o is the concentration in the oil phase (gram MA
per gram of continuous phase) and [MA]w is the concentration
in the aqueous phase (gram MA per gram of dispersed phase).
Gel-Emulsion Stability. The stability of the gel-emulsions was
assessed by visual observation of phase separation and by means
of conductivity measurements as a function of time. Conductivity
was measured by means of a dip cell of platinized platinum
electrodes and a Crison 525 conductimeter.
Interfacial Tension Measurements. Gel-emulsions were allowed
to reach equilibrium at 25 °C and interfacial tensions were
measured by means of a spinning drop tensiometer (Krüss, SITE
04).
3. Results
To perform the diffusion experiments, a model gel-
emulsion was selected, containing the surfactant C16E4
and decane, with a surfactant/oil ratio of 40/60 and 95%
of dispersed phase and prepared as indicated in Section
2.2. MA was incorporated to the solution used as dispersed
phase of the donor gel-emulsion always in a concentration
of a 1% w/v. To obtain a wide enough range of pH values
of the dispersed phase of the gel-emulsion, several aqueous
solutions of NaOH or HCl were prepared.
As mentioned in the Introduction, due to the fact that
MA is a weak acid (pKa ) 3.4)20 the pH of the dispersed
phase influences the degree of ionization of the MA (Figure
2). In addition, this molecule can also exert a buffer effect
on the medium. Using acidic or basic solutions to modify
the pH of the dispersed phase of the gel-emulsion changes
the ionic strength of the medium. Table 1 summarizes the
pH and ionic strength features of several solutions in the
(19) Crank, J. In The Mathematics of Diffusion; Oxford University
Press: U.K. 1975; p 38.
(20) Moffat, A. C.; Jackson, J. V.; Moss, M. S.; Widdop, B.; Greenfield,
E. S. In Clarke’s Isolation and Identification of Drugs in Pharmaceuticals,
Body Fluids and Post-Mortem Material; 2nd ed.; The Pharmaceutical
Press: London, 1986.
∑jmizi2
1
I) (5)
2
where m is the molal concentration and z the electric
charge of the species.
The influence of the pH of the dispersed phase in the
MA diffusion was determined in gel-emulsions prepared
with aqueous solutions at specific pH values. Previous to
the diffusion coefficient determination, formation and
stability of the gel-emulsion with these aqueous solutions
having different pH values was studied. Formation and
stability of gel-emulsions in the water/C16E4/decane and
1% MA aqueous solution/C16E4/decane has already been
studied.14,15 However, it is expected that the presence of
NaOH or HCl modify the formation and stability of the
emulsions. Stability of the gel-emulsion is important, as
the rupture of the gel-emulsion structure would give rise
to a massive release of the MA they contained in the
dispersed drops, and as a consequence, diffusion coef-
ficients would be higher than expected.
3.1. Stability. Stability was assessed by means of two
techniques: conductivity and tensiometry. Conductivity
of the solutions used to prepare the gel-emulsions were
first measured (Table 2). The addition of MA increases
the conductivity of the corresponding solution without
MA, except for NaOH 0.1 N aqueous solution. For this
NaOH concentration the conductivity decreases as a
consequence of the disappearance of the hydroxyl ions,
though the value is still higher than in the other solutions.
The evolution of conductivity as a function of time in gel-
emulsions was then determined. As the external phase of
gel-emulsions is oily, the conductivity is initially close to
zero. Nevertheless, when the aqueous dispersed phase
drops suffer rupture or coalescence, aqueous channels
form, giving rise to an increase in the conductivity of the
system. Therefore, the conductivity measured depends
on the aqueous solution used for the gel-emulsion prepa-
ration, but the initial conductivity value (t ) 0 in Table
3) is not proportional to the conductivity of the original
solution used as the dispersed phase. For example,
although the NaOH 0.1 N solution is the one showing a
higher conductivity (Table 2) once the gel-emulsion is
prepared, its conductivity is lower than the gel-emulsion
formed with HCl 0.01 N (the emulsion displaying higher
conductivities). The slope, S, of the straight line obtained
from the corresponding conductivities at time zero and
after 24 h (Table 2) shows that the rupture of the emulsion
is faster when the dispersed phase contains HCl 0.01 N
or NaOH 0.1 N. On the other hand, NaOH 0.01 N has a
pH Effect on MA Diffusion in Gel-Emulsions
Table 3. Conductivity of Gel-Emulsions at 25 °C
Immediately after Preparation (t ) 0), after 24 Hours (t )
24h), and Slope (S) of the Corresponding Straight Linea
Gel-Emulsion
µS/cm (25 °C)
dispersed phase t)0h t ) 24 h S γ (mN/m)
HCl 0.01 N + 1% MA 0.209 1.921 0.071 0.14 ( 0.01
H2O + 1% MA 0.071 0.237 0.007 0.18 ( 0.01
NaOH 0.01 N + 1% MA 0.024 0.099 0.003 0.19 ( 0.03
NaOH 0.1 N + 1% MA 0.079 0.593 0.021 0.14 ( 0.01
a The final column represents interfacial tensions between the
continuous and the dispersed phases of the gel-emulsion (γ (mN/
m)).
slight stabilizing effect. At equal ionic strength, NaOH is
more effective stabilizing the gel-emulsion than HCl.
Maximum stability was achieved in compositions in which
the MA was incorporated in a NaOH 0.01 N solution. When
the aqueous solution is HCl 0.1 N, both in the presence
and absence of MA, it is not possible to obtain gel-
emulsions. Instead, a transparent isotropic solution is
obtained in which the decane as well as the surfactant are
thoroughly solubilized in the water. To our knowledge,
this behavior has not been described before. This could be
explained by the fact that HCl increases the HLB
temperature. This effect is not very strong at low HCl
concentrations, but at higher concentrations the HLB
temperature increase is enough to destabilize the gel-
emulsion. However, for NaOH the opposite effect has been
described: it decreases the HLB temperature.21 The slight
stability decrease observed at the highest NaOH concen-
tration could be due to the departure from the maximum
stability conditions, without preventing the formation of
the gel-emulsion.
The interfacial tension measurements between the
continuous and the dispersed phase (Table 3) confirm the
same stability tendency as found with the conductivity
measurements; gel-emulsions displaying higher interfa-
cial tensions are more stable according to the correlation
between the interfacial tension and the stability estab-
lished by Chen et al.22 Concerning the interfacial tension
values shown in Table 3, the differences are small and
could be attributed to the effect of the additives on the
HLB temperature. On the other hand the presence of
mandelic acid in the system without other additives
increase the HLB temperature. On the other hand, HCl
has a salting-in effect, thus increasing the HLB temper-
ature, while NaOH combines a salting-out effect with the
change of mandelic acid to mandelate ions.
From the point of view of the diffusion experiments,
both, conductivity and interfacial tension results, suggest
that stability of the emulsions studied is enough not to
alter significantly the diffusion coefficients during the
experimental time of diffusion. In addition, the less stable
emulsions needed a shorter experimental diffusion time.
3.2. Diffusion. Diffusion experiments were performed
as described in the experimental part by contacting gel-
emulsions that differ in the presence of MA, NaOH, or
HCl. Table 4 summarizes the diffusion coefficients ob-
tained as well as the pH of the dispersed phase of gel-
emulsions in the presence and absence of MA. It should
be noticed that MA buffers the medium, so that when the
donor and receptor gel-emulsion are prepared with the
same aqueous solution (except for the presence of MA);
(21) Marszall L. HLB of Nonionic Surfactants: PIT and EIP Methods.
In: Nonionic Surfactants: Physical Chemistry; Schick, M., Ed.; Sur-
factant Science Series; Marcel Dekker: New York, Vol. 23, 1987; p 529.
(22) Chen, H. H.; Ruckenstein, E. J. Coll. Int. Sci. 1991, 145, 260.
Langmuir, Vol. 16, No. 4, 2000 1671
the diffusion of the molecule will equal the pH value of
the receptor gel-emulsions to that of the donor. Therefore,
the degree of ionization keeps constant. However, if the
donor and the receptor emulsions are not prepared with
the same aqueous solution (without considering MA), when
the molecule diffuses into the receptor medium, the pH
will not be the same as in the donor emulsion. As a
consequence, the degree of ionization of MA will change
in the receptor gel-emulsion. This is reflected in the
diffusion coefficients obtained.
Figure 5 shows concentration profiles at basic pH
(12.13-12.53) and at acidic pH (1.92-1.99) for the same
experimental diffusion time (about 17 h). The curves reveal
that when the pH of the dispersed phase of the gel-
emulsion containing MA is very alkaline, (pH ) 12.13),
diffusion takes place very slowly, so that only in the
compartments close to the contact plane MA concentration
has changed, while in the remaining compartments the
concentration remains unchanged. In contrast, when the
pH of the dispersed phase of the gel-emulsion containing
MA is 1.92, diffusion takes place much faster, that is, in
the same experimental time MA diffusion reaches almost
all compartments. In systems with a very small diffusion
coefficient (D < 10-10 m2/s), in which diffusion is so slow
that almost no gradual concentration profile is appreciable
(as in the curve at basic pH in Figure 5), it was necessary
to adjust the diffusion time to longer periods in order to
obtain reliable diffusion coefficients.
When contacting a gel-emulsion at acid pH (2.26)
containing MA with a receptor gel-emulsion at basic pH
(12.53) an unusual concentration profile (Figure 6) was
obtained; a concentration peak appears in the first
compartment of the basic pH receptor gel-emulsion.
However, in the remaining compartments of the receptor
gel-emulsion the concentration almost does not change in
the experimental time tested. In the half of the diffusion
box corresponding to the donor emulsion, which is at acidic
pH, diffusion takes place at a much faster rate than in the
half corresponding to the receptor gel-emulsion at basic
pH. This can be interpreted as two different diffusion rates;
a fast rate in the gel-emulsion having an acidic pH of the
dispersed phase and a second rate much slower in the
gel-emulsion with a basic pH. As a consequence, two
different diffusion coefficients have to be taken into
account. To calculate a diffusion coefficient for this
particular behavior, Fick’s law adapted by incorporating
a partition coefficient between the basic and acidic
emulsions was used.19
As a summary, diffusion takes place in two different
media (Figure 6); in the gel-emulsion initially containing
the whole amount of MA, diffusion is very fast (D ) 4.08
× 10-10 m2/s). However, once the MA molecules diffuse
within the emulsion at basic pH, the diffusion slows
abruptly, to such an extent that the diffusion coefficient
decreases by an order of magnitude (D ) 0.62 × 10 -10
m2/s). It should be noted that the diffusion coefficients
calculated from this concentration profile are very close
to those in a thoroughly acidic medium or a thoroughly
alkaline medium (Table 4).
The explanation for this behavior probably lies with
the change of MA partition coefficient between the aqueous
dispersed phase and the continuous oily phase of the gel-
emulsion as a function of pH. The affinity of the ionized
and nonionized species of MA for water is different.
Although both species are water-soluble, the affinity of
the ionic species for water is higher. At basic pH, the
dissociation equilibrium of MA is shifted toward the
formation of the ionized species favoring its hydrosolu-
1672 Langmuir, Vol. 16, No. 4, 2000 Calderó et al.

Table 4. Diffusion Coefficient of MA at Different pH Values of the Dispersed Phase of the Donor and Receptor
Gel-Emulsiona
donor dispersed receptor pH with MA w % ionized species D × 1010
phase (1% MA) dispersed phase pH without MA donor w receptor (m2/s)
NaOH 0.1 N NaOH 0.1 N 12.13 w 12.53 99.9 0.31 ( 0.01
NaOH 0.1 N H2O 12.13 w 5.89 99.9 w 6.7 0.55 ( 0.5
NaOH 0.01 N NaOH 0.01 N 2.64 w 11.98 14.8 2.2 ( 0.26
H2O NaOH 0.1 N 2.26 w 12.53 6.7 w 99.99 4.1 ( 1.1 w 0.6 ( 0.3
H2O H2O 2.26 w 5.89 6.7 2.6 ( 0.6
HCl 0.01 N HCl 0.01 N 1.92 w 1.99 3.2 3.9 ( 0.7
a See text for more details.

Figure 6. Concentration profile obtained when contacting a

donor gel-emulsion (containing MA) at an acidic pH with a
receptor gel-emulsion (initially without MA) at a basic pH. Both
gel-emulsions (donor and receiver) correspond to the aqueous
solution/C16E4/decane system with S/O ) 40/60 and 95% of
aqueous solution. The curves correspond to the simultaneous
fit of eqs 2 and 3.

Figure 5. Concentration profiles at acidic and basic pH values

of the dispersed phase of the gel-emulsion in the aqueous
solution/C16E4/decane system with S/O ) 40/60 and 95 wt % of
aqueous solution. The lines correspond to the fit of eq 1.
bility. Therefore, higher MA concentrations can dissolve
in aqueous medium compared to concentrations at acid
pH values, at which the formation of ionized species is not
favored.
Table 5 shows the percentage of ionized species at each
pH value of the dispersed phase tested and the partition
coefficient found experimentally. The percentage of ionized
species indicated were calculated according to the Hend-
erson-Hasselbach equation23
[ionized species]
pH ) pKa + log (6)
[nonionized species]
At high pH values, the partition coefficient is low, which
implies low MA concentrations in the oil phase. This would
explain the low diffusion coefficients found in the systems
at pH 12.13. On the other hand, at pH 1.92 most MA is
not ionized, and MA concentration in the oily phase is
higher.
Except for the gel-emulsion formulated with NaOH 0.1
N, partition coefficients are greater than unity. This means
(23) Remington’s Pharmaceutical Sciences, 15th ed.; Mack Publishing
Co.: Easton, PA, 1975; p 269.
that MA concentration is higher in the oil phase than in
the aqueous phase. As MA is a hydrophilic molecule it
would be expected that its concentration would be higher
in the aqueous phase. The reason for the relatively high
partition coefficients of mandelic acid between the oil and
aqueous phase could be due to the high affinity of aromatic
rings for the ethylene oxide groups.24,25 In the system with
NaOH 0.1 N the partition coefficient is lower than unity,
pointing out that MA is located mainly in the aqueous
dispersed phase.
4. Discussion
To discuss the results it will be useful to make explicit
the different states in which the probe molecule can be
solubilized. The first distinction stands on the species
present, nondissociated molecules and ionized molecules,
the latter in their location in gel-emulsions.
The ionized species will be best stabilized in an aqueous
environment. This can be either the interior of the
emulsion droplets or the interior of the microemulsion
droplets present in the continuous phase of the gel-
emulsion. If all MA is present in ionized form, only these
two states are possible and the solubility of mandelate is
the same in both types of water. Then, the partition
(24) Christenson, H.; Friberg, S. E. J. Colloid Interface Sci. 1980, 75,
276.
(25) Pons, R.; Llamas, I.; Calderó, G.; Pérez, L.; Garcı́a-Celma, M.
J.; Azemar, N.; Carrera, I.; Solans, I. Prog. Colloid Polym. Sci. 1997,
105, 244.
pH Effect on MA Diffusion in Gel-Emulsions
coefficient between the continuous and dispersed phase
of the gel-emulsion would correspond to the proportion of
water present in the continuous phase, typically, lower
than 0.2.26 This would correspond to the gel emulsion with
0.1 N NaOH which partition coefficient is reasonably
explained by the previous assumptions. Partition coef-
ficients of NaCl and Na2SO4 using the same surfactant/
oil ratio were found to be 0.23 and 0.20, respectively27
reinforcing this interpretation.
MA in nondissociated form can be also solubilized inside
the emulsion and microemulsion droplets. However, other
locations are also probable for the noncharged species. A
small amount can be solubilized by the oil that constitutes
the continuous phase of the microemulsion, although this
is probably negligible (a partition coefficient of 0.02 exists
between decane and water in the absence of surfactant).15
On the other hand it is known that aromatic rings have
a high affinity for ethyleneoxide groups.24,25 Therefore we
can expect to have mandelic acid associated with the
surfactant molecules at the interfaces of the emulsion
droplets and at the interfaces of the microemulsion
droplets as well as to the monomeric surfactant present
in the continuous phase of the microemulsions. The
possible distribution between these three states is not
absolutely clear. Partition coefficients of MA as a function
of oil-to-surfactant ratio suggested that the MA was mainly
associated one to one with the surfactant molecules that
form the microemulsion droplets27 and not with the
monomeric surfactant. There is no apparent reason for
the association to be only with the surfactant present at
the microemulsion interfaces and not with the surfactant
stabilizing the emulsion droplets. However, the surfactant
stabilizing the emulsion droplets corresponds to a small
proportion except for systems with more than 98% water
content12 and, therefore, the MA associated to these
surfactant molecules would account for only a small
proportion.
Even if partition coefficients favor the location in the
microemulsion phase, most of the MA present in the gel-
emulsions is in the emulsion droplets. For instance, a
partition coefficient of 3 and a water weight fraction of 0.9
implies that 80% of the MA still remains in the water
droplets that constitute the dispersed phase of the
emulsion.
For diffusion to take place in these systems it is clear
that the probe molecules have to change their solubili-
zation state through the diffusion process. First, consider
the diffusion of MA within the water domains (emulsion
droplets or micromulsion droplets). Noting that the
diffusion coefficient of MA in water is 8.6 × 10-10 m2s-1,14
and the global diffusion coefficient in gel-emulsions is
much lower, it can be considered that the diffusion within
the water domains would not have influence on the global
diffusion coefficient except as the limiting fastest rate of
diffusion. MA diffusion in oil could be fast, of the same
order of the diffusion coefficient in water; however, the
low solubility hinders this diffusion path. Diffusion of MA
associated with monomeric surfactant in the oil continuous
phase of the microemulsion could be of about half of the
diffusion coefficient of MA in the oil; however, as stated
before, previous results suggest that this association is
low. MA associated with the emulsion interfaces would
probably not diffuse as such but could be interchanged
with molecules at both sides of the interface. The strength
of this interaction could be the cause of the different
permeability of MA found for different surfactants.15 MA
(26) Pons, R. Ph.D. Thesis. Barcelona, 1992.
(27) Plaza, M. Bs.C. Thesis. Barcelona, 1997.
Langmuir, Vol. 16, No. 4, 2000 1673
Table 5. Partition Coefficients in the Gel-Emulsions (P)
and Percentage of Ionized Form as a Function of the pH
of the Dispersed Phase Calculated According to the
Henderson-Hasselbach Equation
dispersed phase
% ionized species
composition Ph (mandelate) P
HCl 0.01 N + 1% MA 1.92 3.2 4.0 ( 0.2
H2O + 1% MA 2.26 6.7 4.4 ( 0.2
NaOH 0.01 N + 1% MA 2.64 14.8 2.8 ( 0.1
NaOH 0.1 N + 1% MA 12.13 ∼100 0.21 ( 0.02
Figure 7. Schematic illustration of the mechanism involving
diffusion of a hydrophilic molecule in W/O highly concentrated
emulsions.
associated with the surfactant present in the continuous
phase of the microemulsion could be the preferred diffusion
path. In previous investigations we suggested the separa-
tion of the diffusion coefficient in two contributions;
micellar transport through the microemulsion and ex-
change of MA between the emulsion droplets and the
microemulsion. The diffusion coefficients obtained for the
micellar transport through this separation of contributions
were of the right order of magnitude.15 The overall process
can be pictured as in Figure 7. The water droplets play
the role of reservoir of diffusing molecule that diffuses to
the continuous phase and it is the gradient within the
continuous phase that is the driving force of the global
diffusion process.
The effect of pH on the diffusion coefficients of MA in
gel-emulsion can be attributed to the effect of pH on the
distribution of MA between the different domains of the
system. High pH implies a high degree of ionization and,
as a consequence, the partition coefficient of MA changes
to a lower presence in the continuous phase. With this
interpretation, the results shown in Table 4 are easily
understood.
The transfer of MA from a 0.1 N NaOH gel-emulsion
to a gel-emulsion of the same composition is the slowest,
corresponding to the lowest partition coefficient (Table
5). In this case the concentration of hydroxide is so high
that the weak acid only slightly buffers the media and the
diffusion could be considered to take place at constant pH
conditions. The transfer from the same gel-emulsion to a
gel-emulsion without additive is faster. MA diffusing in
the water will rapidly lower the pH. In this setup we have
two different conditions, a slow diffusion at one side and
a faster diffusion at the other. The overall diffusion
coefficient is faster than the diffusion coefficient corre-
sponding to the media with high pH and that of the
unbuffered system. The transfer in a system in which
0.01 N NaOH is present in both the releasing and the
receptor emulsion is quite similar to the system in which
no hydroxide is added. As the MA is still able to buffer the
1674 Langmuir, Vol. 16, No. 4, 2000
system, the pH is similar for both systems. At the point
that MA is transferred, the pH will change to acidic. As
the pH is slightly higher for the system containing NaOH,
the partition coefficient is lower and, therefore, the
diffusion coefficient. When adding HCl to the system the
pH is slightly lower, there are no significant differences
in the partition coefficient but the diffusion coefficient
increases. It should be noted that the limiting diffusion
coefficient would be that of MA in water; therefore, the
diffusion coefficient could not increase indefinitely. Finally
we discuss the interesting diffusion pattern produced by
contacting an emulsion with mandelic acid as an additive
with a gel-emulsion with 0.1 N NaOH as an additive. This
experiment produces the concentration profile shown in
Figure 6. Qualitatively, the behavior can be understood
as a fast diffusion coupled with slow diffusion. However,
we have to consider the accumulation of MA at the contact
point of both emulsions. This peak of concentration is due
to the lower chemical potential of the ionized species as
compared to the nonionized species. MA diffuses through
the gel-emulsion that does not contain NaOH, once MA
reaches the basic solution, its diffusion coefficient drops
by an order of magnitude. To treat the mathematical
problem of diffusion we have considered two media in
which, at equilibrium, the probe molecule partitions with
a constant k. This partition coefficient is related to the
partition coefficients between the continuous and dis-
persed phase of each emulsion according to
[(1 - φ1) + φ1/P1]
k) (7)
[(1 - φ2) + φ2/P2]
Where the subscripts 1 and 2 refer to the two emulsions
in contact.
The line in Figure 6 corresponds to the fit of eqs 2 and
3 with the same set of parameters to the experimental
points. The means for a series of six replicates are shown
in Table 4 for the diffusion coefficients D1 and D2. Both
diffusion coefficients are close to the ones obtained
independently in more uniform pH conditions, 4.1 com-
pared with 2.6 and 0.6 compared with 0.3. The value of
k is 0.19 ( 0.04. Taking into account the respective
partition coefficients at both sides of the gel-emulsion we
can calculate the respective concentrations of MA in the
continuous phase of both gel-emulsions. For the gel-
emulsion containing only MA the relative concentration
Calderó et al.
is 3.8 while in the gel-emulsion containing 0.1 N NaOH
the relative concentration is 0.22. This global partition
coefficient between emulsions would then be 0.06, which
is reasonable, compared with the experimental value of
0.19.
The effect of pH on the diffusion coefficient of MA
explained based on its effect on the partition coefficient
between the continuous and dispersed phases of gel-
emulsions, agrees with the observed behavior induced by
changing the partition coefficient through the addition of
electrolytes.15
5. Conclusions
The diffusion of MA within highly concentrated emul-
sions (gel-emulsions) has been studied by putting in
contact two emulsions that differ only in the presence of
the diffusing molecule. Diffusion coefficients were deter-
mined from the concentration profiles by fitting them to
Fick’s equation with the appropriate boundary conditions.
The effect of pH of the aqueous phase of gel-emulsions
has been analyzed. The diffusion coefficients have been
found to depend strongly on the MA partition coefficient,
while stability of the gel-emulsion, which is similar in the
gel-emulsions studied, does not much influence diffusion.
The results obtained allow proposing a mechanism by
which diffusion takes place in gel-emulsions. Diffusion in
these systems can be described by means of a mechanism
consisting of two simultaneous stages: the passing of the
diffusing molecule through the interfacial film of the
dispersed phase drops and the diffusion in the continuous
phase. The limiting stage of the whole process is the
passage of the molecule through the interfacial film, as
MA transport in the continuous phase is straightforward.
Therefore, the higher the concentration of the diffusing
molecule in the continuous phase the faster the diffusion.
Diffusion in the continuous phase can be explained by
means of micellar transport, diffusion of nonionized species
of MA in the pseudo-oil phase of the W/O microemulsion,
and also the transport of MA linked to monomeric
surfactant.
Acknowledgment. Financial support from DGCICYT
(grant QUI96-0454) is gratefully acknowledged. Gabriela
Calderó acknowledges CIRIT for financial support.
LA990971W