Application of Thermal Analysis to Study the Compatibility

of Sodium Diclofenac with Different Pharmaceutical Excipients

BOGDAN TITA,1* ADRIANA FULIAS,1 GEZA BANDUR,2 IONUT LEDETI,1DUMITRU TITA1
1
University of Medicine and Pharmacy Victor Babe, Faculty of Pharmacy, Eftimie Murgu Square 2, Timioara, 300041, Timisoara,
Romania
2
Politehnica University of Timioara, Industrial Chemistry and Environmental Engineering Faculty, 2 Victoriei Square, 300006,
Timioara, Romania

Thermal analysis is a routine method for analysis of drugs and substances of pharmaceutical interest.
Thermogravimetry / derivative thermogravimetry (TG/DTG) and differential scanning calorimetry (DSC) are
thermoanalytical methods which offer important information about the physical properties of drugs (stability,
compatibility, phase transitions, polymorphism, kinetic analysis etc). In the present work, TG/DTG and DSC
were used as screening techniques for assessing the compatibility between sodium diclofenac (DC) and its
physical association as binary mixtures with some common excipients. Based on their frequent use in
pharmacy, several different excipients as: starch, microcrystalline cellulose (PH101 and PH102), colloidal
silicon dioxide, lactose (monohydrate and anhydre), polyvinylpyrrolidone (povidone K30 or PVP), magnesium
stearate and talc were blended with DC. Samples were prepared by mixing the analyte and excipients in a
proportion of 1:1 (w:w). In order to investigate the possible interactions between the components, the TG/
DTG and DSC curves of DC and each selected excipient were compared with those of binary mixtures, in
order to evaluate any possible solid state modification. The Fourier transformed infrared spectroscopy (FTIR) and X-ray powder diffractometry (XRPD) were used as complementary techniques to adequately
implement and assist in interpretation of the thermal results. On the basis of DSC results, confirmed by FT
IR and X-ray analyses, sodium diclofenac was found to be incompatible with lactose monohydrate,
respectively anhydre, povidone K30 and magnesium stearate.
Keywords: sodium diclofenac, thermal analysis, compatibility, excipient-drug interaction

Diclofenac sodium {2-[(2,6-dichlorophenyl)aminophenyl]acetate} is a potent non-steroidal antiinflammatory drug (NSAID), therapeutically used in
inflammatory and painful diseases of rheumatic and nonrheumatic origin. The anti-inflammator y activity of
diclofenac and most of its other pharmacological effects
are related to the inhibition of the conversion of arachidonic
acid to prostaglandins, which are mediators of the
inflammatory process. Diclofenac is a potent inhibitor of
cyclo-oxygenase in vitro and in vivo, thereby decreasing
the synthesis of prostaglandins, prostacyclin, and
thromboxane products [1,2]. The structural formula for
sodium diclofenac is shown in figure 1.
Fig.1. The chemical
structure of the
sodium diclofenac

The structure of diclofenac consists of a phenylacetic

acid group, a secondary amino group, and a phenyl ring,
both ortho positions of which are occupied by chlorine
atoms. Moser et al. [3] studied 36 congeners of diclofenac
as inhibitors of cyclooxygenase and the in vivo inhibition of
rat adjuvant arthritis and found that both activities can be
explained by lipophilicity and twisting of the two aromatic
rings. These findings allowed the rationalization of the high
activity of diclofenac [46].

Incompatibility between drugs and excipients can alter

stability of drugs, thereby, affecting its safety and/or
efficacy. Drug-excipient compatibility testing at an early
stage helps in the selection of excipients that increase the
probability of developing a stable dosage-form. In particular,
the low availability of drug and the time constraints
associated with the early stages of formulation
development have made such predictability particularly
desirable [711].
Despite the importance of drug-excipient compatibility
testing, there is no universally accepted protocol for this
purpose. The term thermal analysis refers to a group of
techniques in which a physical property of a substance
and/or a reaction product is measured as a function of
temperature whilst the substance is subjected to a
controlled temperature program [1215].
In our previous papers we provided the importance of
the thermal analysis in estimation on the thermal behaviour
of different pharmaceuticals, respectively their possible
interaction with excipients [1624].
Differential scanning calorimeter (DSC) technique
involves the application of a heating or a cooling signal to a
sample and a reference, can evaluate the energy
associated with various thermal events (e.g., melting, glass
transition temperature, crystallization, etc). This method
has been extensively reported in the literature for testing
compatibility of excipients with number of drugs [13
15,25]. The use of DSC has been proposed as a rapid
method for evaluating the physico-chemical interaction
between two components. However, the caution needs to
be exercised in the interpretation of DSC results. This is

* email: bogdantita@yahoo.com
REV. CHIM. (Bucharest) 62 No. 4 2011

http://www.revistadechimie.ro

443

because of temperature conditions required, superior to

ambient temperature, respectively the lack of moisture.
Therefore, the use of other analytical techniques, such as
FT-IR spectroscopy, X-ray powder difractometry and
scanning electron microscopy (SEM) as complementary
tools to assist in the interpretation of DSC findings is
necessary [2628].
Though DSC cannot replace chemical methods for
quantitative determination of drug concentration in longterm stability test, it gives fast and adequate data to classify
acceptable and unacceptable excipients through the
appearance, shift, or disappearance of endothermic or
exothermic peaks, as well as variations in the relevant
enthalpy values, in DSC profiles of drug-excipient
combinations.
In two previous works, it was studied the thermal
stability and kinetic analysis of sodium diclofenac under
non-isothermal [17], respectively isothermal conditions
[24].
In this work, the sodium diclofenac characterization and
compatibility studies have been investigated using a variety
of techniques including thermal analysis (TG/DTG and
DSC), Fourier transform infrared spectroscopy (FTIR) and
X-ray powder diffraction (XRPD).
Experimental part
Materials and samples
The sodium diclofenac (DC) and the excipients: starch;
microcrystalline cellulose PH 101 (MC101) and PH 102
(MC102); colloidal silicon dioxide (CSD); lactose
monohydrate (lactose); lactose anhydre (lactose);
polyvinylpyrrolidone K30 (PVP K30 or PVP); magnesium
stearate (MS) and talc were obtained from Terapia S.A./
Ranbaxy, Cluj-Napoca, Romania as pure compounds, able
to be used for medical purpose.
Physical mixtures of diclofenac with each selected
excipient were prepared in the 1:1 (w:w) ratio by simple
mixture of the components in an agate mortar with pestle
for approximately 5 min.

Methods
Thermal analysis
The TG/DTG/DTA curves were recorded using a
Netzsch-STA 449 TG/DTA instrument in the temperature
range of 20500C, under a dynamic atmosphere of nitrogen
(20 mLmin1) and at a heating rate () of 10C . min1,
using platinum crucibles and weighed 20 mg of samples.
DSC experiments were carried out with a Netzsch
differential scanning calorimeter, model DSC204, using
aluminium crucibles with approximately 3 mg of samples,
under dynamic nitrogen atmosphere (50 mLmin1) and a
heating rate of 10Cmin1, up to a temperature of 500C.
Fourier transformed infrared spectroscopy (FTIR) and Xray diffraction
FTIR spectra of drug, excipients and drug-excipients
blends were recorded on a PerkinElmer Model 1600
apparatus using KBr discs in the range of 4000400 cm1.
Xray diffraction patterns (XRPD), for the same category
of substances, were obtained with a Bruker D8 Advance
X-ray diffractometer using MoK radiation (Zr filter on the
diffracted beam, 50 kV and 40 mA) in a BraggBrentano
:2 configuration, with Soller and fixed slits and a NaI
(Tl) scintillation detector. The measurements of 2 ranged
between 0 and 30. Data analysis and acquisition were
performed using DIFFRACTplus software from Bruker AXS.
Results and discussions
The TG/DTG and DTA curves obtained for sodium
diclofenac are presented in figure 2.
The first process corresponds to the dehydration and
take place between 42.2 and 87.5C with Tpeak DTG=78.5C
and a mass loss of 8%. The decomposition of sodium
diclofenac occurs in 270390C range with Tpeak DTG=300C
and this process has an exothermal nature.
Over 400C, the TG/DTG curves indicate a slow and
continuous mass loss caused by elementary carbon
formation from decomposition step, as consequence of
the rupture of the aromatic ring.

Fig.2. TG/DTG/DTA curves of pure sodium diclofenac

444

http://www.revistadechimie.ro

REV. CHIM. (Bucharest) 62 No. 4 2011

Fig.3. TG curves of all substances

used in compatibility study

The DTA curve of diclofenac (for =10Cmin1) presents

a sharp endothermic event at 84.4C which corresponds to
the dehydration (Hfus=491.1 J . g-1). Further, it occurs the
melting process (T peak DTA=285.9C), which is an
endothermic process and this process is followed
immediately by an exothermic process corresponding to
the decomposition process.
Compatibility study with excipients
Thermal behaviour of the mentioned excipients is more
or less known that in this paper it was studied the thermal
behaviour of the correspondent mixtures. For this purpose,
the thermal curves of DC and excipients were compared
with the curves obtained for 1:1 (w:w) physical mixtures.

Figures 35 show the TG, DTG and DSC curves of the

substances used in the compatibility study. Each curve
shows a specific behaviour depending on the
characteristics of each excipient.
The TG/DTG curves of starch show a dehydration
between 33120C (m=7.2%; DTGpeak=65C), followed
by the process of decomposition between 295375C
(DTGpeak=325C; m=79.7%). Initially the DSC curve
exhibits a wide endothermic peak representing dehydration
(Tpeak=94C) [9,12,29].
The thermal behaviour of microcrystalline cellulose PH101 and respectively PH-102 is the same. Absorbed water
(about 5%) is lost below 110C, between 35 and 110C,
apparently in a single, endothermic and spread-out process

Fig.4. DTG curves of all

substances used in
compatibility study

Fig.5. DSC curves of all

substances used in
compatibility study

REV. CHIM. (Bucharest) 62 No. 4 2011

http://www.revistadechimie.ro

445

(DSC peak =72C). No other thermal phenomena are

observed before the beginning of decomposition, between
307 and 385C (DTG peak =355C and m=88%),
respectively DSCpeak=320C [9,11,30].
In the case of the colloidal silicon dioxide, on the
thermoanalytical curves, no peak was observed in the
range of 25500C [9,11,31].
The amorphous form of lactose was identified by the
presence of an exothermic peak at 167C, which
represented the transformation of amorphous to crystalline
form. It is followed by two endothermic peaks, one at 210
and the other at 216C. These melting peaks belong to
alpha and beta-lactose respectively. It confirmed the
transformation of the amorphous form of lactose to the
two types of crystalline form by heating [3133].
The 100% crystalline lactose, according to XRPD,
contains and forms.
According to the thermogram, the water-content
(m=4.5%) of -lactose monohydrate is evolved between
100 and 170C (DTG peak =161C). The water-free
compound is stable up to about 265C, then it decomposes
up to 365C and DTGpeak=315C. The DSC curve shows a
first sharp endothermic peak (Tpeak=145C) corresponding
to the dehydration reaction, followed by two endothermic
peaks, from the first sharp endothermic peak
(DSCpeak=215C), which corresponds to the melting of lactose, the second weak peak (DSC peak =224C)
represents the melting of -lactose [9, 11,32,33].
On the DSC curve, the -lactose presents a small
endothermic peak (Tpeak=145C) with an insignificant
mass loss on the TG curve, followed by two peaks, the first
light corresponds to the melting of -lactose (Tpeak=215C),
respectively the second represent the melting of the lactose (Tpeak=224C). The decomposition process takes
place in the temperature range of 275 and 365C
(DTGpeak=312C), accompanied by an endothermic event
on the DSC curve (Tpeak=318C) [9,11,33,34].
The TG/DSC curves of PVP, below 150C display on initial
mass loss of 9%. This mass loss is accompanied by a
broad endothermic phenomena (DSCpeak=82C) over an
ill-defined baseline which makes evaluation of the
dehydration enthalpy quite uncertain. The sample readily
dehydrates and its initial mass depends upon the moisture
content of the atmosphere. Apparently, dehydration is
completed at 110C (DTGpeak=164C) in N2. However, a
second loss stage (2%) begins past 150C and completes
around 250C. Thermal analysis, SEM and XRPD all show
that the compound is in a vitreous phase with glass
transition near 200C. Decomposition begins around 384C
(DTGpeak=442C, m=86%) up to 485C [30,3537].

Simultaneous TG/DSC curves of magnesium stearate

show several dehydration stages below 110C. The first
endothermic effect is due to the release of a small amount
of surface water. Around 50C begins the first dehydration
stage of structural water, which partially overlaps with a
second stage at higher temperature. The overall mass loss
due to surface water and to the first stage is 3%, while
the amplitude of the second stage is1.5% of the initial
mass. DSC curve of magnesium stearate initially show
wide endothermic effect (T peak=75C), representing
dehydration. Melting begin at 110C and produce an
endothermic peak with a shoulder in the high temperature
side which is caused by melting of magnesium palmitate
or high-melting polymorphs. The decomposition of the
sample begin around 311C (DTGpeak=362C) and to 480C,
92.5% of sample mass is lost. Corresponding to the
decomposition process, the DSC curve presents a sharp
endothermic with Tmax=372C [9,30,33,34,37].
The TG/DTG and DSC curves of talc present any
significant events under the conditions in the present work
[9,11,33,34,37].
The experimental data obtained for each excipient
correspond to those from the speciality literature
[9,11,12,2937], which confirms the purity of substances
and the correctness of the used methods.
TG, DTG and DSC curves of the pure diclofenac and the
1:1 drug:excipient physical mixture are shown in figures
68.
In the 1:1 physical mixtures when there is no any
interaction between drug and excipient the Tpeak value of
melting event (DSC curve) and the first stage of the
decomposition (Tonset and Tpeak of TG/DTG curves) should
remain practically unchanged, similarly when the drug is
alone. In this case the thermal profiles of the mixture can
be considered as a superposition of the curves of the
diclofenac and excipients. Thus, in the DSC curve of DC
and mixtures, the Tpeak value of melting, a reference
constant, is the same.
According to the thermal curves (fig.68), especially
DSC curves that provide the most complete information, it
is found some smaller or larger differences (the case of
the mixtures with -lactose, -lactose, PVP and MS)
regards to the melting temperature values and those of
the dehydration, respectively of the thermal decomposition
ranges. Basically, all the other excipients present some
differences, however small, on the melting temperature,
dehydration temperature, respectively the value of the
dehydration enthalpies (table 1). These differences may
be due to the small interactions that have not been
confirmed by FTIR spectroscopy and X-ray diffraction
patterns.

Fig.6. TG curves of
diclofenac and its 1:1
physical mixtures

446

http://www.revistadechimie.ro

REV. CHIM. (Bucharest) 62 No. 4 2011

Fig.7. DTG curves of diclofenac

and its 1:1 physical mixtures

Fig.8. DSC curves of diclofenac and

its 1:1 physical mixtures

In the case of mixtures with lactose monohydrate (lactose), respectively anhydre (-lactose), povidone (PVP)
and magnesium stearate (MS), the DSC curves
demonstrated differences in the thermal profile of the DC,
such as absence of drugs melting event. The TG curves
demonstrated that excipients influence the decomposition
process of the DC by displacing the Tonset, respectively
DTGpeak of the first mass loss event at a lower temperature
than the isolated drug. Frequently, this displacing is due to
structural change and indicates interaction,
incompatibilities between the compounds [3133,36].
The DSC curve of the physical mixture of DC with lactose and -lactose demonstrated the disappearance of
the characteristic DC fusion peak. Initially, the curve
presents a broad and strong peak which corresponds to
the elimination of the adsorbed water, between 45115C
with DSCpeak=76.5C, respectively 84.5C. This event is
followed by a broad and strong peak for the -lactose
which corresponds to the elimination of the crystallisation
water between 125165C (DSCpeak=150C), respectively
a broad and weak peak for the -lactose which
corresponds to the elimination of the crystallinity water
(from -lactose) between 115160C (DSCpeak=137.5C)
(fig.8).
For the DC mixtures with PVP and MS, the DSC curves
show the disappearance of the melting peak of DC
(285.9C). Also, the peaks which correspond to the
dehydration are shifted to higher temperatures (97C,
respectively 89.4C) and the decomposition intervals are
wider. The differences are attributed to the interaction
between the components as happens in the case of PVP
and MS interaction with other drugs [9,11,12,29,30,3739].

REV. CHIM. (Bucharest) 62 No. 4 2011

The results taken from the TG/DTG and DSC curves for
the binary mixtures are collected in table 1.
Increasing values of Hdehydration is due to the addition of
the dehydration effect (in most of the cases), as well as to
of the phenomena of co-crystallization of DC, which is
confirmed by the IR and RX spectra.
The FTIR spectroscopy was used as a supplementary
technique in order to investigate the possible chemical
interaction between drug-excipient and to confirm the
results obtained by the thermal analysis. It is the most
suitable technique of the non-destructive spectroscopic
methods and has become an attractive method in the
analysis of pharmaceutical solids, since the materials are
not subject to thermal or mechanical energy during sample
preparation, therefore preventing solid-state
transformations. The appearance of new absorption
band(s), broadening of band(s), and alteration in intensity
are the main characteristics to evidence interactions
between drug and excipients [7,9,11,33,40,41].
FT-IR spectra were drawn for diclofenac, excipients,
respectively for the corresponding mixtures. Further, it will
be presented only the spectra for the cases where the
thermal analysis indicates a possible interaction, namely:
sodium diclofenac, lactose monohydrate and anhydre,
povidone, magnesium stearate and the corresponding
mixtures (Fig.912).
The DC spectrum was in accordance with the literature,
which in the region of 3500 cm-1 describes a large band
attributed to OH group from the absorbed water as well as
to the NH stretching vibration. In the region of 1650-1500
cm-1, there are four bands which correspond to:
- a strong asymmetrical stretching band of carboxylate
anion (COO);
- NH bending (scissoring) vibration;

http://www.revistadechimie.ro

447

Table 1
THERMOANALYTICAL DATA OF SODIUM DICLOFENAC AND DRUG:EXCIPIENT PHYSICAL MIXTURES

Fig.9. IR spectra of lactose monohydrate, DC

and 1:1 blend as simple mixture of DC and
lactose monohydrate

Fig.10. IR spectra of lactose anhydre, DC

and 1:1 blend as simple mixture of DC and
lactose anhydre

- a strong C=O stretching vibrations. The bands from

1453 and 1393 cm1 correspond to the scissoring vibration
of the CH2 group adjacent to the carbonyl. The doublet from
1305 and 1284 cm-1 corresponds to CO stretching band,
as well as to CN stretching absorption, together with CH
bend (in plane) from aromatic ring. The strong bands from
769, respectively 747 cm-1 correspond to the out-of-plane
CH bend.
The spectra of lactose monohydrate, respectively
lactose anhydre, are virtually identical with the observation
448

that the lactose monohydrate shows a sharp medium band

at 3528 cm -1 due to the vibration of OH bond of
crystallization water. The main bands appear at:
- 3380 and 3343 cm-1, as strong and large band (3500
3000 cm -1) attributed to OH stretch: intermolecular
hydrogen bonded;
- a triplet at 2977, 2933 and 2900 cm-1 that corresponds
to the CH stretch: methylene;
- the range of 14201330 cm-1 corresponding to the O
H bending vibrations (in plane).

http://www.revistadechimie.ro

REV. CHIM. (Bucharest) 62 No. 4 2011

Fig.11. IR spectra of PVP, DC and 1:1 blend as

simple mixture of DC and PVP

Fig.12. IR spectra of MS, DC and 1:1 blend as

simple mixture of DC and MS

- the range of 1260100 cm-1 which characterises the

stretching vibrations CO (in fact COC).
- 892 and 876 cm-1 that corresponds to out-of-plane C
H bend.
In respect of the povidone, it presents the following
bands, at:
- 3460 cm1 a large band attributed to the OH group
from the crystallization water;
- 2977 cm1 that corresponds to the C=O bending;
- 1669 cm1 that corresponds to the carbonyl amidic
group;
- 1495; 1465; 1422 cm 1 these correspond to
asymmetrical vibration (as CH3);
- 1291 cm1 that corresponds to the in-plane CH
bending.
Magnesium stearate presents a weak and large band in
the region 3600-3100 cm-1 (the maximum at 3421 cm-1).
At 2918 and 2850 cm-1, there were observed two sharp
bands with maximum absorption due to the CH2CH3
vibrations. In the 15701468 cm-1 region, it showed an
asymmetric stretch corresponding to the carboxyl anion.
Other bands that must be maintained have their peaks
at 2956 cm-1 corresponding to the asymmetrical vibration
of CH bond in methyl group, respectively those at 721
cm-1 which correspond to rocking deformation (HC
H)n; n>3.
For the binary mixture with -lactose, there were
showed the following differences:
- the disappearance of the bands from 3528, 2978, 2933
and 2900 cm-1, for the -lactose spectrum.
- the bands at 3464 cm-1 (DC), respectively 3380-3340
cm-1 (-lactose) are greatly enlarged, corresponding to the
3650-2500 cm-1 range.
- the bands from 1652452 cm-1 corresponding to DC,
respectively those from 1655403 cm-1 corresponding to
REV. CHIM. (Bucharest) 62 No. 4 2011

-lactose, are grouped into three areas: 1653-1250 cm-1;

1250-915 cm-1 and 915-404 cm-1, from which the last two
in particular are in the form of two wide bands with a low
number for so-called maximum and a lot of shoulders. For
most of the maximums, the intensity is not significantly
reduced.
In the case of the mixture with -lactose, were found
similar differences as for -lactoses mixture. Thus:
- the broad bands for DC (3464 cm-1) and for -lactose
(34543293 cm-1) are greatly enlarged, corresponding to
the range of 36502500 cm-1.
- the triplet bands at 2977; 2901 and 2878 cm-1 from the
spectrum of -lactose disappears.
- the bands from the range: 1652452 cm-1 (DC) and
1600418 cm-1 (-lactose) are grouped into three areas:
1600-1200 cm-1; 1200-870 cm-1 and 870-418 cm-1. In this
case, the first area is in the form of broad bands too, with
less of so-called maximum than the summation of the
two spectra (DC and -lactose).
For the mixture of DC with PVP, it is found that:
- the broad bands at 3464 cm-1 (DC) and 3447 cm-1 (PVP)
are more wider than those corresponding to the range of
37002700 cm -1.
- the relatively large band corresponding to the
maximum 2955-2886 cm-1 from the spectrum of PVP
disappears.
- the intense band at 1662 cm-1 from the PVPs spectrum
disappears.
- the bands from the range: 16041284 cm-1 (DC) and
14961293 cm-1 (PVP) are reduced in number and they
are in the form of a wide band with multiple maximums.
- also the bands from 770452 cm-1 range (DC) and 747
406 cm-1 (PVP) do not return to baseline in the case of the
mixture, forming a band almost as wide at the top as the
base.

http://www.revistadechimie.ro

449

Fig.13. X-ray diffractogram of lactose monohydrate, DC and 1:1

blend as simple mixture of DC and lactose monohydrate.

Fig.15. X-ray diffractogram of PVP, DC and 1:1 blend as simple

mixture of DC and PVP

Fig.16. X-ray diffractogram of MS, DC and 1:1 blend as simple

mixture of DC and MS
Fig.14. X-ray diffractogram of lactose anhydre, DC and 1:1 blend as
simple mixture of DC and lactose anhydre.

In the case of DC-MS mixture, the main change is the

fact that the doublet at 2918 and 2850 cm-1 of MS spectra
with maximum absorption disappears. At the same time,
the two broad bands of 3464 cm-1 (DC), respectively 3421
cm-1 (MS) are greatly enlarged (36502700 cm-1) and they
include the doublet which was mentioned above, but their
intensity is reduced only with 10-15%. Also, the absorption
bands at 1571 and 1468 cm -1 in the MS spectrum
(absorption significantly as approx. 75%) together with the
15761393 cm-1 (MS) are found as a broad band with a
small number of maximums. In the same way, the bands
at 770-408 cm-1 are of the form of a band with the base
wide as the top. The FTIR spectra from the figures 912
indicate some chemical interactions between DC and
mentioned excipients.
To investigate the possible interaction of diclofenac with
-lactose, -lactose, povidone and magnesium stearate,
besides the FT-IR spectroscopy which is a qualitative
analysis technique, the X-ray powder diffraction has been
450

used for qualitative and quantitative identification of

crystallinity [31,32,35,36,39,41]. The X-ray diffraction
patterns of sodium diclofenac, -lactose, lactose,
povidone, magnesium stearate and of the binary mixtures
are shown in figures 1316.
The additional prominent DSC peaks in the mixtures of
the drugs and excipients are a positive indication of
chemical interaction of the drugs with excipients. Such
interaction should result in the partial or complete
disappearance of the reactant phases and appearance of
new phases, which can be inferred from X-ray diffraction
patterns. X-ray diffraction patterns of the mixture, prepared
at room temperature, when compared with those of its
individual components showed appearance of new lines
and disappearance of some of the lines present in the
individual components.
The X-ray patterns of diclofenac-lactose mixture
prepared at room temperature shows the lines in addition
to those present in patterns of the individual components

http://www.revistadechimie.ro

REV. CHIM. (Bucharest) 62 No. 4 2011

Table 2
X-RAY DIFFRACTION DATA FOR DICLOFENAC,
LACTOSE MONOHYDRATE AND
DICLOFENAC LACTOSE MONOHYDRATE (1:1)
MIXTURE

Table 3
X-RAY DIFFRACTION DATA FOR
DICLOFENAC, LACTOSE ANHYDRE AND
DICLOFENAC LACTOSE ANHYDRE (1:1)
MIXTURE

REV. CHIM. (Bucharest) 62 No. 4 2011

http://www.revistadechimie.ro

451

Table 4
X-RAY DIFFRACTION DATA FOR DICLOFENAC,
MAGNESIUM STEARATE AND DICLOFENACMS (1:1)
MIXTURE

(table 2). However, the number of lines present in the XRD

patterns of the individual components was found missing
in the similar pattern recorded for the mixture. The
significant difference in the X-ray patterns of the drugexcipient mixtures compared to those of individual drugs
and excipient indicates possible incompatibility of the
drugs with the excipient, even at room temperature. The
presence of majority of the lines of the parent substances
in the thoroughly ground mixture prepared at room
temperature, however, suggests the interaction of the drug
with the excipient at room temperature, which could
increase with the increased temperature.

452

Also, for the binar y mixture: DC-lactose, the

diffractogram (fig.14) and the X-ray diffraction data (table
3) show the interaction of these two substances. The
number of new lines appeared in DCPVP, respectively
DCMS mixtures are shown in tables 4 and 5. The same
tables indicate disappearance of some of the diffraction
lines of higher, moderate and lower intensities in the
mixture which are originally present in the X-ray diffraction
patterns of the individual components which indicates the
interaction of DC with PVP and MS.

http://www.revistadechimie.ro

REV. CHIM. (Bucharest) 62 No. 4 2011

Table 5
X-RAY DIFFRACTION DATA FOR
DICLOFENAC, PVP AND DICLOFENACPVP
(1:1) MIXTURE

Conclusions
This paper presents an issue of great importance, met
more and more often in the speciality literature: the
compatibility of the drugs with different excipients.
The study refers to the compatibility of the DC with a
range of excipients mentioned in the paper. As methods of
study, there were used: the thermal methods of analysis,
the FTIR spectroscopy and X-ray diffraction patterns.
According to the thermal curves, especially DSC curves,
one can say that all excipients present lower or higher
interactions, with IB. This fact is supported by the
differences between the values of Tdehydration and Tfusion,
respectively of the enthalpies of dehydration.
The disappearance of the characteristic DC fusion peak
for the mixtures with -lactose, -lactose, PVP and MS
certainly shows an interaction with DC. In the same
context, the starch interaction occurs in a certain extent,
while other excipients interaction is unlikely.
Considering that the enthalpies of dehydration are
quantitative data since they may be expressed as a
fractional change, it could be said that all excipients interact
with DC. Taking into account these differences correlated
with the water content of the excipients as well as with
the differences between the values of Tdehydration, it can
sustain the level of interaction which was mentioned above.
The interaction of -lactose, -lactose, PVP and MS with
DC was confirmed by FTIR spectroscopy and by X-ray
diffraction patterns. In terms of starch interaction with DC,
this wasnt confirmed by the two techniques mentioned,
probably because of limited modifications.
REV. CHIM. (Bucharest) 62 No. 4 2011

This study shows the incompatibility of DC with lactose, -lactose, PVP and MS.
References
1. FINI, A., FAZIO, G., BENETTI L., CHEDINI, V., Thermochim. Acta,
464, 2007, p. 65
2. KOVALA-DEMERTZI, D., J. Organomet. Chem., 691, 2006, p. 1767.
3. MOSER, P., SALLMANN, A.,WISENBERG, I., J. Med. Chem., 33, 1990,
p. 2358
4. BOGDAN, D., MORARI, C., Physics Letters A, 366, 2007, p. 454.
5. KENAWI, I.M., BARSOUM, B.N., YOUSSEF, M.A., Eur. J. Pharm. Sci.,
26, 2005, p. 341
6. KENAWI, I.M., J. Mol. Struc., 754, 2005, p. 61
7. NETO, H.S., NOVK, CS., MATOS, J.R., J. Therm. Anal. Cal., 97,
2009, p. 367
8. OLIVEIRA, P.R., STULZER, H.K., BERNARDI, L.S., BORGMANN,
S.H.M., CARDOSO, S.G., SILVA, M.A.S., J. Therm. Anal. Cal., 100, 2010,
p. 277
9. BERTOL, C.D., CRUZ, A.P., STULZER, H.K., MURAKANI, F.S., SILVA,
M.A.S., J. Therm. Anal. Cal., 102, 2010, p. 187
10. LIRA, A.M., ARAJO, A.A.S., BASLIO, I.D.J., SANTOS, B.L.L.,
SANTANA, D.P., MACEDO, R.O., Thermochim Acta, 457, 2007, p. 1
11. BARBOZA, F., VECCHIA, D.D., TAGLIARI, M.P., SILVA, M.A.S.,
STULZER, H.K, Pharm. Chem. J., 43, 2009; p. 363.
12. MORA CORVI, P., CIRRI, M., MURA, P., J. Pharm. Biomed. Anal., 42,
2006, p. 3
13. NETO, H.S., BARROS, F.A.P., DE SOUSA CARVALHO, F.M., MATOS,
J.R., J. Therm. Anal. Cal. 2010;doi:10.1007/s10973-009-0419-3.

http://www.revistadechimie.ro

453

14. MOURA, E.A., CORREIA, L.P., PINTO, M.F., PROCOPIO, J.V.V., DE

SOUSA F.S., MACEDO R.O., J. Therm. Anal. Cal., 2010, doi 10.1007/s
10973-009-0473-X.
15. PICCIOCHI, R., DIOGO, H.P., DA PIEDADE, M.E.M., J. Therm. Anal.
Cal., 99, 2010, p. 391
16. TIA, B., FULIA, A., MARIAN, E., TIA, D., Rev. Chim. (Bucharest),
60, no. 4, 2009, p. 419
17. TIA, B., FULIA, A., MARIAN, E., TIA, D., Rev. Chim. (Bucharest),
60,no. 5, 2009, p. 524
18. FULIA, A., TIA, B., BANDUR, G., TIA, D., Rev. Chim. (Bucharest),
60, no. 10, 2009, p. 1079
19. TIA, B., FULIA, A., RUSU G., TIA, D., Rev. Chim. (Bucharest),
60,no. 11, 2009, p. 1210
20. TIA, B., FULIA, A., BANDUR, G., RUSU G., TIA, D, Rev. Roum.
Chim., 55, 2010, p. 553
21. TIA, B., FULIA, A., TIA, D., Rev. Chim. (Bucharest), 61, no. 11,
2010, p. 1037
22. TIA, D., FULIA, A., TIA, B., J. Therm. Anal. Cal., in press.
23. TIA, B., FULIA, A., SZABADAI, Z., RUSU G., BANDUR, G., TIA, D,
J. Therm. Anal. Cal., in press
24. TIA, B., FULIA, A., TEFNESCU, M., MARIAN, E., TIA, D., Rev.
Chim. (Bucureti), in press
25. YING, Y.C., YI, L., CHENG, Z.J., DAN, Z., Biol. Trace Elem. Res.,
122, 2008, p. 82
26. BANNACH, G., CERVINI, P., CAVALHEIRO, E.T.G., IONASHIRO, M.,
J. Therm. Anal. Cal., 2010; doi:10.007/s10973-009-0595-1
27. ILIESCU, T., BAIA, M., MICLU, V., Eur. J. Pharm. Sci., 22, 2004, p.
487
28. BANNACH, G., CERVINI, P., CAVALHEIRO, E.T.G., IONASHIRO, M.,
Thermochim. Acta, 499, 2010, p.123.

454

29. BERNARDI, L.S., OLIVEIRA, P.R., MURAKAMI, F.S., SILVA, M.A.S.,

BORGMANN, S.H.M., CARDOSO, S.G., J. Therm. Anal. Cal., 97, 2009,
p. 729
30. TOMASSETTI, M., CATALANI, A., ROSSI, V., VECCHIO, S., J. Pharm.
Biomed. Anal., 37, 2005, p. 949
31. MOYANO, M.A., BROUSSALIS, A.M., SEGALL, A.I., J. Therm. Anal.
Cal., 2010;doi 10.1007/s 10973-009-0351-6
32. BALESTRIERI, F., MAGRI, A.D., MAGRI, A.L., MARINI, D., SACCHINI,
A., Thermochim. Acta, 285, 1996, p. 337
33. CIDES, L.C.S., ARAJO, A.A.S., SANTOS-FILHO, M., MATOS, J.R., J.
Therm. Anal. Cal., 84, 2006, p. 441
34. OLIVEIRA, G.G.G., FERRAZ, H.G., MATOS, J.S.R., J. Therm. Anal.
Cal., 79, 2005, p. 267
35. MARINI, A ., BERBENNI, V., PEGORETTI, M., BRUNI, G.,
COFRANCESCO, P., SINISTRI, C., VILLA, M., J. Therm. Anal. Cal., 73,
2003, p. 547
36. BRUNI, G., AMICI, L., BERBENNI, V., MARINI, A., ORLANDI, A., J.
Therm. Anal. Cal., 68, 2002, p. 561
37. NUNES, R.S., SEMAAN, F.S., RIGA, A.T., CAVALHEIRO, .T.G., J.
Therm. Anal. Cal., 97, 2009, p. 349
38. STULZER, H.K., TAGLIARI, M.P., CRUZ, A.P., SILVA, M.A.S.,
LARANJEIRA, M.C.M., Pharm. Chem. J., 42, 2008, p.215
39. STULZER, H.K., RODRIGUES, P.O., CARDOSO, T.M., MATOS, J.S.R.,
SILVA, M.A.S., J. Therm. Anal. Cal., 91, 2008, p. 323
40. FREIRE, F.D., ARAGAO, C.F.S., DE LIMA E MOURA T.F.A., RAFFIN,
F.N., J. Therm. Anal. Cal., 97, 2009, p. 355
41. ABBAS, D., KALOUSTIAN, J., ORNETO, C., PICCERELLE, P.,
PORTUGAL, H., NICOLAY, A., J. Therm. Anal. Cal., 93, 2008, p.353
Manuscript received: 15.12.2010

http://www.revistadechimie.ro

REV. CHIM. (Bucharest) 62 No. 4 2011