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Indian Journal of Chemical Technology Vol. 16, September 2009, pp. 426-430
Estimation of Ibuprofen solubilization in cationic and anionic surfactant media:
1Department of Chemistry, Berhampur University, Bhanja Bihar, Berhampur 760 007, India
2Department of Chemistry, Roland Institute of Technology, Surya Vihar, Golanthara, Berhampur 761 008, India
Email: [email protected]; [email protected]Received 17 June 2008; revised 29 June 2009
Drug solubility is an important parameter for efficient drug delivery and absorption. Ibuprofen, α-methyl-4-[2-methyl-
propyl] benzene acetic acid is a NSAID group of drug with antipyretic and analgesic properties. It has poor solubility in water. Its solubilisation properties in presence of cetyltrimethylammonium bromide (CTAB) and sodiumdodecyl sulphate (SDS) have been studied. Saturation solubilities in aqueous and aqueous-micellar media have been studied spectrophotometrically by measuring absorbance at 264 nm. Plot of solubility versus [SDS] shows a maximum in the pre-micellar region followed by the linear relationship between the variables in the region past critical micellar concentration (cmc). With CTAB, the solubility- [surfactant] profile shows double maxima, one each in pre- and post- micellar region. Appropriate explanation has been forwarded and the nature of solubilizate-surfactant interaction suggested. The pKa values of ibuprofen determined pH-metrically in aqueous and aqueous-SDS media have been used to supplement the inference. The association constant values and free energy change of solubilisation are reported.
Keywords: Micelle, Surfactant, UV Spectroscopy, Absorption, Solubility, Ibuprofen
Drug solubility in aqueous medium is an important
solubility of a poorly soluble compound in surfactant
parameter for efficient drug delivery and absorption1,2.
media remains very low till the cmc is reached and
Of particular significance in this regard is the role
played by surfactant solutions because of their ability
concentration, here a maximum is obtained in the
to increase the solubility of sparingly soluble
solubility versus [surfactant] graph in the pre-micellar
substances in water1. In aqueous solution, surfactant
region with either SDS or CTAB as surfactant. Once
molecules form organized assemblies or micelles over
the cmc is reached the usual linear relationship
a narrow concentration range called critical micellar
between the two variables is observed only with SDS.
concentration (cmc)3. The core of the micelles is
However, with CTAB, the solubility-[surfactant]
formed by hydrocarbon chain and is hydrophobic in
profile shows a double maximum, one each in pre-
nature while the outer polar head groups are
and post-micellar regions. Thus the theory for
hydrophilic and hence remain hydrated. Increase in
increased solubilisation in surfactant media4,8 as the
solubility of non-polar compounds in surfactant
reversible interaction with the micelles of a surfactant
medium is ascribed to their incorporation into either
in water to form a thermodynamically stable isotropic
the palisade layer or inner core of the micelles.
solution is not sufficient. Based on the observations a
However, compounds with some degree of polarity
plausible theory to the mechanism of solubilisation of
may be adsorbed at the micellar water interface4,5.
ibuprofen in surfactant media is provided. Association
Ibuprofen, α-methyl-4-[2-methylpropyl] benzene
constants of the solubilizate with micelles as well as
acetic acid, which is a non-steroidal, anti-
dissociation constants of ibuprofen are also reported.
inflammatory drug with analgesic and antipyretic
properties, is selected for the present study. It has a
Experimental Procedure
poor solubility in water6, 0.049 mg/mL. The present
The drug ibuprofen was received as a gift from
paper deals with solubilization properties of ibuprofen
Apex Laboratories, Chennai. The cationic surfactant
in both cationic (cetyltrimethylammonium bromide,
(cetyltrimethylammonium bromide, CTAB) was from
CTAB) and anionic (sodiumdodecyl sulphate, SDS)
BDH while the anionic surfactant (sodiumdodecyl
surfactant media. Contrary to the observations4,7 that
sulphate, SDS) was from Qualigens. Saturated
BHATTAMISHRA & PADHY: ESTIMATION OF IBUPROFEN SOLUBILIZATION IN SURFACTANT MEDIA
solutions of ibuprofen in water and in surfactant
minor change in the cmc value9 (9.2×10-4 mol dm-3).
solutions of different concentrations were prepared by
The change in the extents of solubilization with
adding excess of the drug to the desired medium. To
change in the concentrations of both SDS and CTAB
ensure saturation solubility, each solution was
is shown in Figs 3 and 4. In either case at pre-micellar
subjected to shaking and this was accomplished in
concentrations, there is an initial rise in solubility with
three different ways; (i) by mechanical means, (ii)
increase in surfactant concentration. The solubility
using a magnetic stirrer or (iii) centrifuging at
reaches a maximum then decreases and rises again at
different rpm to a maximum of 4500 rpm at 27ºC.
about the cmc value of the surfactant. With SDS as
These saturated solutions were left for 24 h to
the surfactant, in the region of [surfactant] > cmc, the
equilibrate before being taken for spectroscopic
solubility increases almost linearly with the increase
estimation. Remi C-24BL Cooling Centrifuge was
in concentration of the surfactant. However, with
used for centrifuging the sample solutions.
CTAB, a second maximum is obtained in the plot of
The electronic spectrum of ibuprofen recorded by
solubility versus [surfactant] in the region [surfactant]
Shimadzu UV-visible spectrophotometer 1700, showed
two peaks at 264 and 272 nm with extinction
The relationship for association of a substrate
coefficients as 299 and 257 mol-1 dm3 cm-1 respec-
molecule in micellar medium is given by,
tively. The concentration of ibuprofen in each
saturated solution, measured (24 h) after mixing, was
determined from its absorbance value at 264 nm. The
conductance values of the saturated solutions of
The equilibrium constant KM, also known as
ibuprofen in water and in surfactant solutions of
Systronics model 306 conductometer with extension conductivity cell, type CD-30 at 27ºC. The pKa values of ibuprofen in aqueous and aqueous-SDS media were determined pH metrically using Systronics µ 361 pH meter with extension glass, calomel electrode and temperature probe.
Results and Discussion
Figures 1 and 2 show the conductance values of a
number of solutions of SDS and CTAB respectively in presence of ibuprofen. The break at [SDS] = 4×10-3 mol dm-3 shows that the presence of ibuprofen
in the surfactant medium lowers its cmc value9
Fig. 2 – Conductance values of CTAB solutions in presence of
(8.1×10-3 mol dm-3). However, with CTAB there is
Fig. 1 – Conductance values of SDS solutions in presence of
Fig. 3 –Solubilization of ibuprofen as a function of [SDS] at 27ºC.
INDIAN J. CHEM. TECHNOL., SEPTEMBER 2009
Fig. 4 –Solubilization of ibuprofen as a function of [CTAB]
Fig. 5 – Plot of P versus (Dt – cmc) for ibuprofen solubilized in
both [SDS] and [CTAB] media are included in
where [SW] and [SM] stand respectively for the
The presence of maxima in the plots of solubility
solubility of the substrate (ibuprofen) in water and in
versus [surfactant] in the region where [surfactant]
the surfactant medium; [DM] is equal to [D]– cmc, [D]
<cmc, may be explained on the basis of complex
being the molar surfactant concentration in the
formation between the substrate (ibuprofen) and the
medium. This is because below cmc, the surfactant
surfactant monomer11. As a result, the solubility
molecules are largely in the monomeric form but
increases. However, as the micelles start forming, the
above cmc, these take up mostly the micellar form,
substrate-surfactant complex breaks and so the
the monomer concentration being approximately
solubility decreases12,13. The electronic spectrum of
equal to the cmc. The micelle-water partition
ibuprofen in water and in 1.4×10-2 mol dm-3 SDS
coefficient10, which is the ratio of substrate
solution is shown in Fig. 6. There is no shift in
concentration in micellar medium to that in water
absorption maxima and the spectra are by and large
the same. Resemblance of the absorption spectra of a
solubilizate in the micellar medium to that in polar
solvent implies a polar environment of the substrate in
the micelle5. Obviously in an anionic surfactant like
SDS, the linear increase in solubility of ibuprofen
with increase in [SDS] in the post-micellar region
P = K {[D ]−cm }
may be ascribed to incorporation of the former in the
so that the plot of partition coefficient against
The following experiments further establish the site
[Dt]-cmc will be a straight line of slope KM (Fig. 5).
of adsorption of iburprofen in SDS micellar medium.
Since in a micellar medium, the substrate is
When SDS is added to ibuprofen solution an increase
considered to be partitioned between two phases, the
in pH is recorded. The pH change is smaller, in the
micellar phase and the aqueous phase, the standard
pre-micellar region but increases rapidly above the
cmc to reach a saturation value at [SDS] concen-
tration of about 5×10-2 mol dm-3. This implies that the
acid dissociation of ibuprofen is hindered by the
ibuprofen in a number of SDS solution with SDS
where Pm is the molar partition coefficient between
>cmc have been measured pH-metrically. There is a
steady, almost linear increase in pKa values with
BHATTAMISHRA & PADHY: ESTIMATION OF IBUPROFEN SOLUBILIZATION IN SURFACTANT MEDIA
Table 1—Solubility of ibuprofen in aqueous solutions of SDS and CTAB at 27ºC.
a: Either hand shaken or magnetically stirred b: Centrifuged at 4500 rpm.
Table 2—Variation in the pKa value of ibuprofen with
carboxylate anion of ibuprofen may compete with the anionic micelle for the H+ ion to form the neutral polar ibuprofen molecule, which then easily gets attracted to the micellar surface. This in turn explains
both the observed phenomenon i.e. the increase of pKa
value and solubility of ibuprofen with increasing SDS
Fig. 6 – Electronic spectra of ibuprofen in water and in SDS solution (1.4×10-2 mol dm-3).
The solubility pattern of ibuprofen in CTAB up to
increasing [SDS] (Table 2), which further supports
the cmc is explained exactly in a similar manner as in
the above view that SDS micelles hinder deproto-
nation. Several factors may be attributed to this
concentration increases, the concentration of the
behaviour14. Firstly, there may be a concentration
ibuprofen increases in the micellar phase and so the
gradient of protons between the bulk and interface.
solubility increases. The cationic micellar surface
Again the dielectric constant on the micellar surface is
attracts the carboxylate anion of ibuprofen whose
different from that of the bulk; the same on the
formation is facilitated by formation of HBr, a
micellar interface of SDS has been estimated14,15 as
stronger acid compared to ibuprofen. Here the
32. In a medium of low dielectric constant compared
electrostatic force is more effective compared to that
to bulk water, acid dissociation is likely to be
in SDS medium. This is evident from the decrease in
hindered. Further, an anionic micellar surface like that
pKa value of ibuprofen with increase in [CTAB]. But
of SDS is expected to attract positively charged
after micelles incorporate all the reactant molecules,
species or polar neutral compounds. In such a
further increase in micellar concentration only
case rather protonation will be encouraged. The
produces dilution effect and so the solubility
INDIAN J. CHEM. TECHNOL., SEPTEMBER 2009
decreases forming the second maximum in the
at concentration of about 5×10-3 mol dm-3 and
5×10-4 mol dm-3 for SDS and CTAB surfactants
Table 1 shows some interesting results. When
respectively. As a result, the solubility of ibuprofen
centrifuged, solubility of ibuprofen in water increases
decreases. The release of dissolved ibuprofen at a
greatly, but its solubility in SDS solution of any
particular concentration of the surfactant is extremely
concentration is greatly suppressed compared to hand
useful in drug delivery. However, the temperature and
shaken or magnetically stirred solubility. The
pH effects on solubility of ibuprofen in surfactant
decrease in the rate of increase of solubility on
media need to be conducted for better understanding
centrifuging, is found to be directly proportional to
the rpm value. It is felt that churning of the surfactant
solution, especially at high rpm, most likely prevents
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