Characterization of Ibuprofen as a Nontraditional Plasticizer

of Ethyl Cellulose
C. DE BRABANDER,1 G. VAN DEN MOOTER,2 C. VERVAET,1 J.P. REMON1
1
Laboratory of Pharmaceutical Technology, Ghent University, Harelbekestraat 72, 9000 Gent, Belgium
2
Laboratorium voor Farmacotechnologie en Biofarmacie, K.U. Leuven, Campus Gasthuisberg O N, Herestraat 49,
3000 Leuven, Belgium

Received 8 November 2001; revised 4 February 2002; accepted 8 February 2002

ABSTRACT: This study describes the characterization of the plasticizing properties of

ibuprofen (IBP) on hot-melt extruded ethyl cellulose (EC). The thermal behavior of hot-
melt extrudates containing 0, 5, 10, and 20% (w/w) IBP was evaluated using modulated
temperature differential scanning calorimetry. By means of comparison, co-evaporates
containing the same concentrations of IBP and EC, were also evaluated. Both methods
yielded solid solutions having one glass transition temperature indicating compatibility
between drug and polymer. A similar decrease in glass transition temperature was
noticed with increasing IBP concentration in the solid solutions prepared via both
methods, indicating its plasticizing effect. The plasticizing efficiency was of the same
magnitude as for the traditionally used plasticizers. Infrared spectroscopy was performed
for better understanding of the chemical interactions in the molecular dispersions and
confirmed the existence of hydrogen bonds between IBP and EC. Overall, the study has
highlighted the plasticizing properties of IBP on EC during hot-melt extrusion. 2002
Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 91:16781685, 2002
Keywords: ibuprofen (IBP); ethyl cellulose (EC); plasticizer; hot-melt extrusion; solid
solution; MTDSC

INTRODUCTION Whereas the behavior and properties of tradi-

The use of plasticizers is one of the most efficient
ways to modify the thermal and mechanical
properties of polymers. Plasticizers are often low-
molecular-weight compounds that lower the glass
transition temperature (Tg) and convert rigid
polymers into flexible ones. To be effective, a plas-
ticizer must distribute itself between the polymer
chains and interact with functional groups,
thereby reducing the interaction between the
polymer chains and softening the matrix.1 Plas-
ticizers are required for nearly all polymers used
in film coating to reduce the polymers brittleness,
improve flow, import flexibility and increase
toughness, strength, as well as shear resistance.
Correspondence to: J.P. Remon (Telephone: 32-9-264-8054;
Fax: 32-9-222-8236; E-mail: jeanpaul.remon@rug.ac.be)
Journal of Pharmaceutical Sciences, Vol. 91, 16781685 (2002)
2002 Wiley-Liss, Inc. and the American Pharmaceutical Association
tional plasticizers such as phthalates have been
well documented, some drugs were found to have a
plasticizing effect. After film formation via organic
solution or aqueous dispersion casting, Eudragit1
E 100 was plasticized by lidocaine HCl,2 whereas
Eudragit1 RS 30 D was plasticized by methylpar-
aben and chlorpheniramine maleate.3 Lidocaine
HCl was also able to lower the Tg of hot-melt
extruded Eudragit1 E 100 films,2 whereas hydro-
cortisone and chlorpheniramine maleate softened
the matrix structure of hydroxypropylcellulose.4
In 1994, Bodmeier and Paeratakul5 reported on
the migration of ibuprofen (IBP) toward an ethyl
cellulose (EC)-based coating (Aquacoat1) after
curing. This was attributed to the affinity of IBP
for EC, and an intermediate seal coating had to be
applied to reduce the drugs diffusion into the
coating. Wu and McGinity3 defined the affinity of
IBP for polymers like acrylate polymers as being

1678 JOURNAL OF PHARMACEUTICAL SCIENCES, VOL. 91, NO. 7, JULY 2002

 THERMAL BEHAVIOR OF HOT-MELT EXTRUDATES WITH IBP
a non-traditional plasticizer during film forma-
tion. These plasticizing properties were physically
and mechanically determined and IBP was iden-
tified as having a plasticizing effect on acrylate
polymers in the making of films from aqueous
colloidal polymer dispersions.3
The discovery of these drugs as being nontradi-
tional plasticizers should be situated in the
research area of coated solid dosage forms,
where possible drug migration out of the dosage
form into the coat might take place over time,
inducing stability problems. Therefore, coatings
are exhaustively studied to elucidate the drugs
effect (possible plasticizer) on the relationship
between Tg, minimum film forming temperature,
and processing conditions.
The plasticizing effect of drugs could provide a
technological advantage during a hot-melt ex-
trusion process because extrusion of a hydroxy-
propylcellulose-polyethyleneoxide mixture6 was
possible at a lower temperature when vitamin E
TPGS (TPGS, D-a-tocopheryl polyethylene glycol
1000 succinate) was added because this drug
lowered the Tg of the polymer mixture.
A similar phenomenon was observed when this
technique was applied during the development
of sustained release mini-matrices with EC as
carrier material and IBP as model drug. During
hot-melt extrusion, IBP/EC blends containing
60% IBP could unexpectedly be extruded at a
temperature of 608C, far below the Tg of EC
(1338C). This behavior of IBP/EC blends during
hot-melt extrusion led to the assumption that IBP
interacts with EC, lowering the polymers Tg.
Although hot-melt extrusion is recently receiv-
ing increased attention in the pharmaceutical
field, the influence of IBP as a nontraditional
plasticizer on the thermal behavior of hot-melt
extruded EC has not been investigated yet.
The aim of this work was to examine the plas-
ticizing effect of IBP on EC extrudates. By means
of comparison, co-evaporates consisting of IBP
and EC were also prepared. Both the extrudates
and the co-evaporates were studied using modu-
lated temperature differential scanning calori-
metry (MTDSC).
MATERIALS AND METHODS
Materials
IBP (Fig. 1) (diameter: 25 mm) (pharmaceutical
grade) was obtained from Knoll Pharmaceuticals
1679
Figure 1. Chemical structure of IBP.
(Nottingham, UK). EC (Fig. 2) [ethoxyl content:
4849.5% (w/w); viscosity: 911 MPa
s (5% solu-
tion in toluene/EtOH, 80:20, 258C)] was pur-
chased from Fluka Chemie (Bornem, Belgium)
(preparation of co-evaporates) and from Dow
Chemical (Midland, MI) (preparation of extru-
dates). Methylene chloride was obtained from
Acros Organics (Geel, Belgium).
Preparation of IBP/EC Co-Evaporates
To prepare solid dispersions containing 0, 5, 10,
and 20% (w/w) IBP, the drug, and the polymer
were dissolved in methylene chloride. The poly-
mer solutions (total solids content: 0.5 g in
150 mL) were transferred into a Teflon flask, and
a rotavapor (Buchi EL, Flawil, Switzerland) was
used to remove the solvent under reduced pres-
sure at 408C. The films were peeled from the PFA
(per fluor alkoxy) surface of the flask and stored in
a vacuum oven at 408C for 2 days. Subsequently,
the films were pulverized in a mortar using liquid
nitrogen, further dried at 508C until a constant
weight, and stored in a desiccator before subject-
ing the samples to thermal analysis.
For Fourier-Transform infrared (FT-IR) analy-
sis, binary molecular dispersions were prepared
by dissolving drug and polymer in methylene
chloride. The solids fraction of these 5% (w/v)
solutions contained either IBP (10, 20, and
30%, w/w), diethyl phtalate, or dibutylsebacate
Figure 2. Chemical structure of EC.
JOURNAL OF PHARMACEUTICAL SCIENCES, VOL. 91, NO. 7, JULY 2002
1680 DE BRABANDER ET AL.

(10%, w/w). The solutions were spray-dried using The Netherlands) and analyzed by a MELZ LCD-
a self-constructed laboratory spray dryer.7 After 212 refractive index detector. The flow was
collection, the spray-dried powder was further maintained at 1 mL/min. Polystyrene of known
dried at 508C until a constant weight and stored molecular weights was used as reference material.
in a desiccator until IR analysis. In both cases, the
residual solvent was less than 2 ppm. Thermal Analysis
The Tg of pure IBP was determined by heating
Hot-Melt Extrusion of IBP/EC Mixtures 5-mg samples [closed aluminum pans (TA Ins-
truments, Brussels, Belgium)] at 108C/min to
Blends of IBP/EC in ratios of 0:100, 5:95, 10:90,
908C, followed by quench cooling to 1008C (indi-
and 20:80 (w/w) were prepared in a planetary
cated cooling rate on the apparatus: 1008C/min)
mixer (Kenwood Chef, Hampshire, UK). These
and subsequent reheating at 58C/min to 858C
powder blends were processed using a laboratory
using a Perkin Elmer DSC-7 differential scanning
scale co-rotating twin screw extruder (MP 19 TC-
calorimeter (Perkin Elmer, Norwalk, CT) equipped
25; APV Baker, New Castle-under-Lyme, UK),
with an LNCA (liquid nitrogen cooling accessory)
with a length-to-diameter ratio of 25. The IBP/EC
(Perkin Elmer). Data were treated mathematically
blends were put in the hopper and extruded. The
using the Pyris Software version 3.80 (Perkin
extrusion parameters were set at a screw speed of
Elmer).
30 rpm and a powder feed rate of 360 g/h. The
The thermal behavior of the polymer films and
temperature of the five heating zones along the
the extrudates was evaluated using a modulated
extrusion barrel was set at 80-100-130-130-1308C
(temperature) differential scanning calorimeter
from the first heating element toward the die exit.
(2920 Modulated DSC; TA Instruments, Leather-
After extrusion, the extrudates were cooled and
head, UK) equipped with a refrigerated cooling
stored at room temperature. The extrudates were
sytem. The flow rates of helium through the DSC
randomly sampled, ground into a fine powder
cell and of dry nitrogen through the refrigerated
using a mortar and liquid nitrogen and subjected
cooling sytem unit were 40 and 150 mL/min,
to thermal analysis.
respectively. Samples (611 mg) were run in
aluminum open pans supplied by TA Instruments
Chemical Stability (Leatherhead, UK). The experimental method
consisted of an initial 20-min isothermal period
The chemical stability of IBP after hot-melt
at 608C to ensure the complete removal of methyl-
extrusion was determined by using high-pressure
ene chloride followed by an equilibration period at
liquid chromatography (HPLC). The HPLC sys-
258C. During the subsequent heating run, the
tem (Merck Hitachi, Darmstadt, Germany) con-
following experimental parameters were used: an
sisted of an L-7100 solvent pump and a reversed
underlying heating rate of 28C/min from 258 to
phase C-18 column (Licrospher1, 125  4 mm
2008C, a modulation amplitude of 0.2128C, and a
5 mm). Online analysis was performed at 221 nm
period of 40 s. Temperature calibration was per-
using an L-7450 diode array spectrophotometer. A
formed with octadecane, benzoic acid, and indium
solution of 0.1 M KH2PO4 (adjusted to pH 7.0 with
standards; enthalpic calibration was performed
2 M NaOH) and acetonitrile (ratio 11:4, v/v) was
with indium standard, whereas calibration of heat
used as mobile phase. All chemicals were of
capacity was performed with a sapphire standard.
analytical or HPLC grade.
The results were analyzed using the TA Instru-
Ten milligrams of hot-melt extruded IBP was
ments Universal Analysis Software (TA Instru-
dissolved in 100 mL of ethanol. An aliquot of
ments, Leatherhead, UK). Measurements were
100 mL of this solution was injected onto the
performed in duplicate (unless otherwise stated).
column to determine the IBP concentration. Using
Both Tg values (midpoint values) are reported.
these data, the percentage of IBP present in the
sample was calculated.
IR Spectroscopy
The molecular weight of EC before and after
hot-melt extrusion was determined by gel permea- FT-IR spectra were obtained using a PerkinElmer
tion chromatography using Waters equipment 2000 FT-IR system using the KBr disk method
(Brussels, Belgium). Polymer solutions in tetra- (0.4% sample in a 200-mg KBr disk). The scan-
hydrofuran (10 mg/mL) were injected into a Mixed ning range was 5004000 cm1 and the resolution
C5 mm column (Polymer Laboratories, Heerlen, 1 cm1.

JOURNAL OF PHARMACEUTICAL SCIENCES, VOL. 91, NO. 7, JULY 2002

 THERMAL BEHAVIOR OF HOT-MELT EXTRUDATES WITH IBP
RESULTS AND DISCUSSION
Although the possible plasticizing effect of IBP on
EC was noticed during hot-melt extrusion of a
formulation containing 60% drug, this composi-
tion could not be used for an in-depth study
because the endothermal melting peak of the
crystalline fraction still present in the matrix
overlapped with the thermal phenomena of inter-
est. Consequently, for a fundamental understand-
ing of the effect of IBP on the Tg of EC, IBP/EC
blends at a lower drug concentration were re-
quired, hence co-evaporates and hot-melt extru-
dates were prepared at drug concentrations of 5,
10, and 20% (w/w).
Chemical Stability
As both the drug and polymer were subjected to
heat and mechanical stress during hot-melt extru-
sion, their chemical stability was evaluated.
HPLC analysis showed that 98.97  1.40% (n 7)
IBP was recovered after extrusion. In addition,
the UV spectrum of extruded IBP coincided with
the spectrum of unprocessed drug as shown by
diode array analysis (correlation: 0.9983).
The polydispersity indices (Mw/Mn) of 3.406
and 3.129 and a similar molecular weight (Mw) of
64,000 for hot-melt extruded and unprocessed EC,
respectively, indicated no significant changes in
the width of the molecular weight distribution.
This confirmed that no degradation occurred dur-
ing extrusion of EC at these conditions. Follonier
and co-workers8 reported that degradation of EC
was only observed at higher temperatures: an
onset decomposition temperature of 1908C, a 2.1%
weight loss at 2008C, and a discoloration above
2058C. Moreover, the relative stability of EC after
various treatments was already reported by other
authors.9,10
Thermal Analysis of IBP/EC Co-Evaporates
The Tg of unprocessed EC powder was 133.38C
(Fig. 3, profile A), whereas the Tg of the EC film
(without plasticizer) ranged between 128.6 and
129.38C (Fig. 3, profile B). Dubernet and co-
workers11,12 also reported a slight decrease in Tg
of EC microspheres compared with EC powder
and concluded that this phenomenon only pro-
vided information about polymer aging. The
addition of IBP, a highly crystalline drug with a
melting endotherm of about 768C resulted in an
amorphous transparent polymer film, indicating
that film casting yielded a molecular dispersion or
1681
Figure 3. MTDSC curves of EC powder (A), molecu-
lar dispersions containing 0% (B), 5% (C), 10% (D), and
20% (E) (w/w) IBP.
solid solution. The effect of IBP on the Tg of EC is
shown in Figure 3. The Tg decreased with
increasing concentrations of IBP, as the drug
included in the polymer film acted as a plasticizer.
Adding 5, 10, and 20% (w/w) of IBP lowered the Tg
interval of EC to 105.8109.2 (n 2), 84.687.1
(n 3), and 52.866.28C (n 5), respectively.
Increasing the amount of IBP from 0 to 5% and
from 5 to 10% resulted in a decrease of the Tg of
approximately 208C.
The DSC curves of all formulations (Fig. 3) only
revealed a single Tg, indicating compatibility
between drug and polymer. It is well known that
Tg of compatible mixtures varies between the Tg
values of the individual components.
The experimental Tg values (square symbols,
Fig. 4) were compared with those predicted (solid
line, Fig. 4) according to the Gordon-Taylor
equation13:
Tg1 w1 KTg2 w2
Tg mix
w1 Kw2
where w1 and w2 are the weight fractions of IBP
and EC, respectively, and Tg1 and Tg2 are the
glass transition temperatures of IBP and EC,
respectively. After quench cooling of liquid IBP,
the Tg of amorphous IBP was determined at
43.68C. The Tg of an EC co-evaporate without
plasticizer was used in this equation. K is defined
as the ratio of the differences in expansion co-
efficient (Da) at Tg of the drug and polymer.
However, when weight fractions are used instead
of volume fractions, and when it is assumed that
DaTg is constant, K becomes14:
JOURNAL OF PHARMACEUTICAL SCIENCES, VOL. 91, NO. 7, JULY 2002
1682 DE BRABANDER ET AL.
Figure 4. Tg as a function of IBP concentration (%;
w/w) in solid dispersions with EC. The full line
represents the theoretical values calculated with the
Gordon Taylor equation for binary compatible mix-
tures. The symbols represent the experimental values
determined by MTDSC: squares and circles for the co-
evaporates and extrudates, respectively.
Tg1 r1
K (F).
Tg2 r2
r represents the density of the amorphous drug
(r1) and of the polymer (r2). The density of EC and
of amorphous IBP, estimated from its crystalline
density reduced by 5%, was measured using a
He-pycnometer (AccuPycTM 1330; Mircomeritics,
Brussels, Belgium).
It is obvious from Figure 4 that the experi-
mental values are lower than the predicted ones
for the co-evaporates. This suggests that the
interactions between drug and polymer are not
of the same magnitude as those between indivi-
dual polymer or drug molecules, hence the
requirement of volume additivity is not fulfilled
given the structure of the polymer and drug. The
negative deviation from the predicted ideal be-
havior might be caused by hydrogen bonding
between drug and polymer, resulting in a change
of free volume of the system.15 The bonding
strength within the new structure is weaker
than between identical molecules.
In general, to obtain good miscibility between
two components, the solubility parameters should
be similar or differ less than  6.5 Mpa1/2.16 The
solubility parameter of IBP was calculated at
19.5 Mpa1/2.17 The calculated value for EC was re-
ported to be 21.1 Mpa1/2.18
To get a better understanding of the physical
structure of the molecular dispersions, IR analy-
JOURNAL OF PHARMACEUTICAL SCIENCES, VOL. 91, NO. 7, JULY 2002
Figure 5. FT-IR spectra of EC (A), crystalline IBP
(B), () IBP (C), solid dispersion 10% IBP (D), solid
dispersion 20% IBP (E), and solid dispersion 30% IBP
sis was performed. The data are shown in
Figure 5. The IR spectrum of pure crystalline
IBP is characterized by the absorption band
caused by asymmetric stretching of the carbonyl
group at 1722 cm1. The localization of this band
is typical for carboxylic acid groups involved in
cyclic dimerization.
A strong signal in the region of the carbonyl
stretching is also observed in the spectra of the
molecular dispersions. However, in contrast to
pure drug it is located at a higher wavenumber,
1737 cm1. Given the structure of IBP and EC and
taking into account that the polymer has several
proton donor/acceptor possibilities per monomeric
unit, the shift of the carbonyl stretching fre-
quency can be explained by hydrogen bonding
between the two entities, together with a decrease
or absence of cyclic dimerization of the drug.
Similar to the observations made by Taylor and
Zografi19 for indomethacinpolyvinylpyrrolidone
dispersions, the peak at 1737 cm1 can be attri-
buted to non-hydrogen bonded carbonyl. How-
ever, because of the abundance of hydrogen
bonding possibilities on the polymer, it can be
assumed that the hydroxyl group of the drug is
involved in hydrogen bonding with EC. Given the
fact that ether groups are poorer acceptors
 THERMAL BEHAVIOR OF HOT-MELT EXTRUDATES WITH IBP
compared with hydroxyl functions, hydrogen
bonding is likely to occur with the polymer hy-
droxyl function. Whereas the peak at 1635 cm1
originates from the polymer, a second signal as a
function of drug concentration appeared at
1707 cm1: at 10% drug loading, it can be seen
as a shoulder, whereas at 30% drug loading, it is a
distinguishable peak. The ratio of the intensity of
the peak at 1737 cm1 to that at 1707 cm1 de-
creases with increasing drug concentration. The
location of the peak at 1707 cm1 suggests that it
is caused by stretching vibration of another
carbonyl. To explain the origin of this band, the
possibility of formation of enantiomers of IBP
was investigated. IR analysis of () IBP showed a
peak corresponding to its carbonyl stretching at
1706 cm1 (Fig. 5). This band corresponds to the
extra signal observed in the molecular disper-
sions, thus strongly suggesting that () IBP is
gradually formed during extrusion with EC.
Thermal Analysis of IBP/EC Extrudates
Extrusion of IBP/EC mixtures yielded glassy and
transparent extrudates. Complete miscibility be-
tween drug and polymer was not limited to film
formation, but was also obtained during hot-melt
extrusion, because the thermograms demonstra-
ted a single glass transition during heating
(Fig. 6). The effect of IBP on Tg of the extrudates
is shown in Figure 6. A decrease in Tg was ob-
tained with increasing IBP concentrations, indi-
cating its plasticizing effect during hot-melt
extrusion. The Tg (n 2) ranged between 126.3
127.8, 103.7108.4, 78.378.7, and 57.664.58C
for the extruded IBP/EC formulations containing
0, 5, 10, and 20% (w/w) drug, respectively.
Figure 6. MTDSC curves of EC extrudates contain-
ing 0% (A), 5% (B), 10% (C), and 20% (D) (w/w) IBP.
1683
Comparing the Tg shifts of the co-evaporates
and the extrudates showed that the plasticizing
efficiency of IBP was similar in both methods,
indicating that intense intermolecular mixing
not only occurred with the solvent evaporation
method (after complete dissolution of drug and
polymer), but also during the hot-melt extrusion
process ensuring complete miscibility of IBP and
EC. Contrary to these data, Aitken-Nichol and
co-workers2 reported that lidocaine HCl was a
more effective plasticizer in solution cast films
rather than in the extruded films during the
production of thin, flexible acrylic films for topical
drug delivery. They suggested that intermolecu-
lar mixing was better in a solution cast film than
in a highly viscous melt. Secondly, at each IBP/EC
ratio, similar Tg widths were noticed for the co-
evaporates and the extrudates. But the Tg width
increased with increasing IBP concentrations.
Both production techniques yielded a Tg width
lying between 35408C and 47538C for the 0:100
and 20:80 IBP/EC (w/w) compositions, respecti-
vely. A comparable DCp decrease for the co-evapo-
rates/extrudates was seen with increasing IBP
concentrations for each IBP/EC ratio. A negative
deviation from the predicted ideal behavior was
also noticed for the solid solutions formed after
hot-melt extrusion (Fig. 4, circles).
During this procedure, a powder formulation
(consisting of IBP and EC) became a solid solu-
tion under the combined influence of heat
(heating segments of the extrusion barrel) and
shear (screw speed).
The plasticizing effect of IBP on EC was com-
pared with two traditional plasticizers, diethyl
phtalate and dibutylsebacate. The Tgs of the solid
dispersions containing 10% (w/w) dibutylsebacate
and diethyl phtalate were 83.1 and 89.38C,
respectively, establishing the equivalent plasti-
cizing efficiency of IBP as the Tg value of an EC/
IBP co-evaporate containing 10% IBP varied
between 84.6 and 87.88C.
It was interesting to notice that a second
endothermic transition was observed in the DSC
heating curves of EC at approximately 1788C
(Fig. 3, profiles A and B; Fig. 6, profile A). Subse-
quent heatingcooling steps through this transi-
tion demonstrated the reproducibility of this
event (Fig. 7). A similar reproducible endothermic
transition was observed by Nyamweya and Hoag20
for hydroxypropyl cellulose. Although not explain-
ed, they hypothesized that this event was either
due to melting of a crystalline phase or a liquid
crystal isotropic transition. In the case of EC,
JOURNAL OF PHARMACEUTICAL SCIENCES, VOL. 91, NO. 7, JULY 2002
1684 DE BRABANDER ET AL.
Figure 7. DSC curves (A) heating run 108C/min, (B)
cooling run 108C/min) of EC.
hot-stage microscopy using polarized light,
undoubtedly indicated that the endothermic
transition was caused by melting of a crystalline
phase and that no liquid crystalline phase was
present (data not shown). The enthalpy of fusion
of the crystalline phase was determined at 4.2
( 0.2) J/g, whereas the crystallization enthalpy
measured after cooling of the liquid phase at a
rate of 108C/min was 3.6 ( 0.3) J/g. This crystal-
line phase gradually decreased with increasing
IBP concentration in the polymer matrix (Fig. 7).
At 20% drug loading, the crystalline melting
transition completely disappeared. This observa-
tion shows that incorporation of IBP influences
the physical structure of the polymer, not only
the amorphous regions, but also the crystalline
domains are affected. Indeed, melting of the pure
polymer leads to reversible partial crystallization,
whereas in the presence of the drug, partial crys-
tallization is no longer possible because the drug
is homogeneously dispersed on a molecular level
in the polymer matrix.
CONCLUSIONS
The present study showed that IBP was able to
plasticize EC-based films and extrudates as Tg
shifted toward lower temperatures with increas-
ing IBP concentrations. The presence of a single
concentration-dependent Tg lying between the
Tgs of the individual components establish-
ed complete miscibility between IBP and EC.
MTDSC was an excellent method for measuring
this change in Tg. The FT-IR results proved the
presence of hydrogen bonding between IBP and
EC.
JOURNAL OF PHARMACEUTICAL SCIENCES, VOL. 91, NO. 7, JULY 2002
The main advantage of the plasticizing pro-
perties of IBP during hot-melt extrusion is its
ability to reduce the extrusion temperature,
hence the drug itself can be seen as an excellent
processing aid in the development of sustained
release mini-matrices.
ACKNOWLEDGMENTS
The authors thank Loes Verheyden for valuable
assistance during the experiments.
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JOURNAL OF PHARMACEUTICAL SCIENCES, VOL. 91, NO. 7, JULY 2002