Qualis A1 (Engenharia II)

F.I= 1,052

Clay Minerals (2001) 36, 541546

Preparation of drug-montmorillonite
UV-radiation protection compounds by
gas-solid adsorption
C. DEL HOYO1,2, M. A. VICENTE2,3,{ AND V. RIVES1,2,*
1
Departamento de Qumica Inorganica, Universidad de Salamanca, 37008-Salamanca, Spain, 2 Unidad Asociada
IRNASA(CSIC)-Universidad de Salamanca, c/ Cordel de Merinas, s/n, 37008-Salamanca, Spain, and 3 Instituto de
Recursos Naturales y Agrobiologa, Consejo Superior de Investigaciones Cientficas,c/ Cordel de Merinas, s/n, 37008-
Salamanca, Spain

(Received 15 June 2000; revised 12 February 2001)

AB ST R ACT : Ethyl cinnamate/montmorillonite intercalation complexes were obtained by gaseous

adsorption of the drug on the clay surface. They were characterized by powder X-ray diffraction,
differential thermal and thermogravimetric analyses and by visible-UV and IR spectroscopies. It was
found that after 1 day of adsorption, most of the drug enters the interlayer space of the clay by
substitution of water molecules, and is removed only after heating at high temperature. In addition, a
portion is physisorbed on the external surface of the crystallites, being removed easily below 1008C.
The interlayer complex improves the protecting ability of the pure clay or the pure drug against
ultraviolet radiation, specially in the so-called C range (290 190 nm).

KEYWORDS: montmorillonite, ethyl cinnamate, drug-clay interaction, gas-solid adsorption, UV radiation

protection.

The interactions between organic compounds and
clay minerals have been widely studied within clay
science (Mortland, 1970; Theng, 1974; Cairns-
Smith & Hartman, 1986; Rausell-Colom &
Serratosa, 1987). The ability of clays and clay
minerals to adsorb and desorb organic molecules is
well known, and makes them very attractive as
carriers and supports for pharmaceuticals
(Porubcan, 1978; Hermosn et al., 1981; Vicente,
1981; Sanchez Martn et al., 1981; Sayalero, 1982;
White & Hem, 1983; Forteza et al., 1989; Vicente
et al., 1989). The increasing demand for products to
be used as radiation blocks against the so-called C
ultraviolet radiation (290 190 nm) and protection
against the skin cancer it causes, has led to study of
the interactions between organic molecules (already
* E-mail: vrives@gugu.usal.es
{
Deceased
DOI: 10.1180/0009855013640007
known and used as radiation absorbers) and clay
minerals. In previous papers (del Hoyo, 1995; del
Hoyo et al., 1996a,b, 1998) we described the use of
drug-clay systems prepared by melting the drug
onto the clay or grinding the clay and the drug
together to form radiation blocks. These methods
are different from the method widely used to
intercalate (or simply to adsorb) drugs and other
organic molecules onto the surface of clays, i.e.
adsorption from the liquid state or from liquid
solutions, and we have shown that the methods lead
to solids with absorbing properties similar to those
of the systems prepared by conventional adsorption
from solutions. Here we report, however, an
alternative method, consisting of adsorption from
the gas phase onto the layered clay, taking
advantage of the relatively low boiling point of
the drug (2718C at atmospheric pressure, but ~608C
at 0.25 Torr) because of its neutral molecular
character.

# 2001 The Mineralogical Society

542 C. del Hoyo et al.
CH=CH-COOCH2CH3
FIG. 1. Ethyl cinnamate.
Ethyl cinnamate (Fig. 1) is a neutral molecule
currently used in creams as protection against solar
radiation. It is liquid at ambient temperature, highly
soluble in alcohol, acetone and benzene and
insoluble in water (Merck Index, 1989). Due to its
insolubility in water, intercalation of this drug in
layered clays cannot be carried out by conventional
methods using aqueous solutions; being liquid, it
cannot be ground with the clay, the method we
proposed for other drugs. In the present work, we
have studied the ethyl cinnamate/montmorillonite
systems obtained by gaseous adsorption of the
former onto the latter, and their possible application
as ultraviolet radiation blocks. The method is
probably faster and cleaner than adsorption from
organic solutions.
EXPERIMENTAL
The montmorillonite used in this work was
purchased from Fluka (Switzerland, Mont-
morillonite K-10, ref. 69866), and the <2 mm
size-fraction saturated with Na+ was selected. Its
specific surface area is 274 m2 g 1. Its cation
exchange capacity is 86 mEq/100 g and, as shown
below, it contains small amounts of illite and
kaolinite impurity. Ethyl cinnamate was also
purchased from Fluka (ref. 96410), and was used
without further purification.
The gaseous adsorption method was carried out
in a desiccator connected to a vacuum pump and
kept at 608C to vapourize the drug. Six glass dishes
were placed in the upper part of the desiccator, each
one containing 500 mg of montmorillonite, and a
beaker containing 10 ml of ethyl cinnamate was
placed in the lower part. Samples were removed
after 10 and 30 min, 1 and 2 h, and 1 and 3 days,
respectively. Once prepared, the samples were
characterized by different experimental techniques.
The powder X-ray diffraction (XRD) patterns of the
unoriented solids were recorded using a Siemens
D-500 diffractometer, with a Cu anode (Ka1, l =
1.54050 A) equipped with a graphite monochro-
mator (30 mA, 40 kV, 2 7082y range, scan step
0.058, 1.5 s); the diffractometer was connected to a
DACO-MP microprocessor and to a personal
computer; the pattern corresponding to the Ka1
radiation was separated from the diffraction
originated by radiation Ka2 using the software
facilities of the Difract-AT package. The differential
thermal analysis (DTA) and thermogravimetric
analysis (TG) curves were recorded in DTA-7 and
TG-7 instruments, respectively, from Perkin-Elmer,
and were analysed using the commercial Pyris
program, also provided by Perkin Elmer. About
20 30 mg of sample were used, and the heating
rate was 108C min 1; the analyses were performed
in O2 (from LAir Liquide, Spain); commercial
alumina previously calcined at 13008C was used as
a reference in the DTA experiments. The FT-IR
spectra were recorded in a Perkin-Elmer FT-1730
instrument, using the KBr pellet technique with a
nominal resolution of 4 cm 1 and 100 scans were
averaged to improve the signal-to-noise ratio.
The ability of the systems prepared to absorb
visible-ultraviolet (V-UV) radiation was checked by
recording the V-UV spectra of the solids following
the Diffuse Reflectance technique (V-UV/DR) in
the 900 190 nm range, using a Shimadzu UV-240
spectrophotometer, with MgO as the reference and
a slit of 5 nm.
RESULTS AND DISCUSSION
The XRD diagrams for the original montmorillon-
ite, and for the samples prepared after 10 min, 2 h,
and 24 h adsorption are included in Fig. 2. As
mentioned above, the clay contains small amounts
of illite and kaolinite, as identified by the peaks
recorded at 9.87 and 7.13 A, respectively, and is
rather disordered, as concluded from the broadness
of the peaks. The basal diffraction of mont-
morillonite develops a rather broad peak close to
15.3 A, and this peak does not shift for samples
equilibrated with the drug for 10 min or even 2 h,
suggesting that in these samples the drug has not
entered the interlayer space of the clay or
sufficiently ordered structures have not been
formed. However, the XRD trace for the sample
equilibrated with ethyl cinnammate for 24 h shows
a shift of this peak from its original position, at
15.3 A, to ~20 A, thus indicating that swelling of
the clay has taken place, probably by intercalation
of drug molecules. This result indicates that the
drug is not merely adsorbed onto the external
 Gas-solid adsorption of drugs
FIG. 2. XRD patterns of the original montmorillonite and of the samples obtained after equilibrating with ethyl
cinnamate vapour for 10 min, 2 h and 1 day. The traces have been displaced vertically for clarity.
surface of the clay crystallites, but that it actually
enters the interlayer space of the clay. Most of the
data provided in this paper will refer to the sample
equilibrated for 24 h.
Figure 3 shows the DTA and TG curves for the
original montmorillonite and for the drug/clay
complex (24 h). The DTA curve for the former
shows an intense, rather sharp, endothermic effect
with a minimum at 1068C. The TG curve indicates
a weight loss of ~7% in this temperature range
which corresponds to the loss of interlayer water
molecules from the clay. A second weight loss,
extending up to 6008C, represents ~3% of the
original sample weight. A weak DTA minimum is
recorded at 5008C, corresponding to removal of
structural water from montmorillonite and kaolinite
(MacKenzie, 1970), existing as impurity in the
sample, together with structural dehydroxylation of
montmorillonite. A weak endothermic effect is
recorded at ~9008C, corresponding to destruction
of the layered structure.
The thermal effects in the DTA curve for the
drug/clay complex (24 h), as shown in Fig. 3, are
noticeably stronger than for the original mont-
morillonite. The endothermic effect originally due
to removal of interlayer water has almost vanished,
and the curve is now dominated by a strong, but
543
structured, endothermic effect with minimum
slightly above 4008C, with shoulders below this
temperature. In fact, this effect seems to begin at
temperatures as low as 1008C. The first shoulder
might be due to removal of physisorbed drug and,
on comparison with the curve for the pure drug (del
Hoyo, 1995), the other shoulders can be ascribed to
consecutive removal of fragments of the drug
molecule. The weight loss recorded up to 2508C
is ~15% of the original sample weight, while in the
case of the pure montmorillonite the value was 7%,
and total weight loss was ~24% (11% for the
original montmorillonite). These results indicate
that adsorption has taken place, but probably in at
least two different forms: one weakly bonded,
which is removed at low temperature giving rise
to the first weight loss, but without involving much
energy (the drug molecules removed in this
temperature range are probably physisorbed on the
external surface of the crystallites), and another
strongly bonded, probably in the interlayer space of
montmorillonite (as suggested by the XRD data
mentioned above), which would be removed at
higher temperature, thus accounting for the intense
endothermic effect around 4008C and the weight
loss recorded between ~250 and 8008C. Removal of
these strongly held molecules probably occurs at
544 C. del Hoyo et al.
FIG. 3. Differential thermal analysis (right) and thermogravimetric analysis (left) curves of montmorillonite (solid
lines) and the sample equilibrated for 1 day with ethyl cinnamate (dashed lines).
the same time as the decomposition of the drug
molecule, accounting for the DTA steps recorded in
this temperature range.
Quantitative calculations of the amount of drug
intercalated in the interlayer of the clay can be
performed using the TG data above described for
the original montmorillonite and for the drug-clay
system. Assuming (see FTIR results below) that
intercalation of ethyl cinnamate has mostly
removed the interlayer water molecules, and that
the amount of structural hydroxyl groups remains
constant, the amount of intercalated drug can be
calculated as ~8 8.6 g drug/100 g montmorillonite.
Figure 4 shows the FT-IR spectra of the original
drug, the original montmorillonite, and the drug/
clay system (24 h).
With respect to the drug, the sharp bands
recorded can easily be ascribed as follows:
-ester function modes: at 1713 cm 1 n(C=O) of
the a,b-unsaturated ester and conjugation of the
aromatic ring with the double bond of the molecule,
and n(C O) at 1203 and 1176 cm 1
-olefinic modes: n(C H) at 3029, out-of-plane
d(C H) at 980, in-plane d(C H) at 1311, and
n(C=C) at 1639 cm 1.
-methyl group modes: n(C H) at 2981 and
2873 cm 1, and d(C H) at 1477 cm 1
-methylene modes: n(C H) at 2937, and d(C H)
at 1465 cm 1
-aromatic ring: n(C H) at 3084 and 3062 cm 1,
out-of-plane d(C H) at 768 and 712 cm 1
-skeletal vibrations at 1578, 1496 and
1450 cm 1.
The spectrum of montmorillonite can be also
interpreted easily: the strong, broad band at
3446 cm 1 is due to the n(OH) mode of structural
and water hydroxyl groups, involved in hydrogen
bonding; the rather sharp peak at 3627 cm 1 is due
to the valence vibration of structural OH groups
(Farmer, 1974). The deformation mode of mole-
cular water is responsible for the medium intensity
band recorded at 1636 cm 1. Bands due to the
lattice vibrations of the silicate are recorded in the
1100 450 cm 1 range (Farmer, 1974). The very
intense band at 1049 cm 1 is due to the Si O Si
stretching; the weak band at 799 cm 1 is due to
Si O stretching, the band at 525 cm 1 is due to
Si O R3+ and R3+ OH vibrations, and the main
band in this low wavenumber region at 469 cm 1 is
due to Si O Fe and Fe OH groups (Cicel &
Kranz, 1981).
With respect to the spectrum of the drug/clay
sample, it should be noted that it resembles the
superimposition of the spectra corresponding to the
drug and to the clay. In fact, sharp bands are simply
developed on the broader peaks due to the clay, but
they do not shift from the positions in the pure ethyl
cinnamate (see Fig. 4). This lack of modification of
 Gas-solid adsorption of drugs 545

FIG. 4. FT-IR spectra of the original montmorillonite, ethyl cinnamate and the sample equilibrated for 1 day. The
traces have been displaced vertically for clarity.

the spectra indicates that the interaction between the montmorillonite. The pure drug shows two broad
drug and the clay is rather weak. It is also worth absorptions, and in the spectrum of the sample
noting that that band due to the deformation mode of equilibrated for 1 day with ethyl cinnamate vapour,
molecular water, originally recorded at 1636 cm 1 a remarkable increase in the energy absorption
in the spectrum of montmorillonite is much weaker,
and might be overlapped by the intense doublet of
the drug at 1713 and 1639 cm 1, suggesting that
intercalation has displaced (probably not completely)
the water molecules from the interlayer space. Such
a displacement may be merely a substitution, but it
will be also favoured by the hydrophobic character
of the drug. Even the relative intensity of the broad
peak due to n(OH) in hydrogen-bonded hydroxyl has
decreased, although a contribution from structural
hydroxyl groups to this band cannot be ruled out.
As mentioned earlier, the ultimate aim of this
work was the preparation of these drug/clay systems
as potential blocks against UV radiation. The V-
UV/DR spectra of the samples prepared after
1 days equilibration with gaseous ethyl cinnamate
are included in Fig. 5. For comparison, the spectra
recorded for the original, unloaded montmorillonite,
and for the pure drug, are also shown.
The original montmorillonite shows a broad
absorption extending into the ultraviolet range FIG. 5. Visible-UV/DR spectra of the original mon-
below ~330 nm, which is ascribed to charge tmorillonite, ethyl cinnamate and the sample equili-
transfer processes in the lattice structure of the brated for 1 day.
546 C. del Hoyo et al.
ability is observed, especially for wavelengths
lower than ~320 nm, i. e. the so-called C range
of UV light. The absorption shown by the drug/clay
system is much larger than that shown by the pure
drug, despite the fact that the amount of drug was
lower in the first case.
CONCLUSIONS
The drug-clay complex obtained following the 24 h
gaseous method shows an appreciable improvement
in the protective properties of ethyl cinnamate and
clay against UV radiation, especially in the high-
energy range (C radiations, 290 190 nm). Results
from the thermal analysis, FT-IR and V-UV
spectroscopies, and XRD have shown that the
drug has entered in the interlayer space of the
clay by substitution of water molecules, although
such an intercalation does not modify substantially
the electronic state of the drug. On the other hand,
because the drug is insoluble in water, it will be
difficult to remove from the clay, and so it should
last longer as a radiation block.
ACKNOWLEDGMENTS
We are grateful to Mrs Pilar Rodrguez, Mr Luis
Fernando Lorenzo, Mr Angel Gonzalez and Mr Jose
Manuel Ordax from IRNA (CSIC) for their help and
collaboration in this work.
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