Taste-masked orally disintegrating tablets of prednisolone/Asian Journal of Pharmaceutical Sciences 2007, 2 (6): 227-238

Preparation and evaluation of taste-masked orally

disintegrating tablets of prednisolone
V. Ananda, *, R. Kandarapub, S. Gargc
a
Department of Pharmaceutics, Seth G. L. Bihani S. D. College of Technical Education, Sri Ganganagar, Rajasthan, India
b
Research and Development, Dr. Reddy’s Laboratories Ltd. (Generics), Bachupally, Hyderabad, India
c
School of Pharmacy, University of Aukland, New Zealand
Received 20 June 2007; Revised 18 September 2007; Accepted 13 October 2007
_____________________________________________________________________________________________________________

Abstract

Purpose: To prepare taste-masked orally disintegrating tablets (ODTs) of prednisolone (PDL) by incorporation of microspheres in the
tablets for use in specific populations viz. pediatrics, geriatrics and patients experiencing difficulty in swallowing. Methods: Microspheres
containing PDL were prepared by the solvent evaporation method using acetone as solvent for pH-sensitive polymer and light liquid
paraffin as the encapsulating medium. Prepared microspheres were characterized with regard to the yield, drug content, particle size and
size distribution, surface features, in vitro drug release and taste. Tablets, prepared by direct compression containing microspheres, were
evaluated with regard to crushing strength, friability, disintegration time, drug content and in vitro drug release and taste. Results: The
results obtained showed that the average size of microspheres is influenced greatly by the speed of stirring. Microspheres prepared by the
solvent evaporation method in acetone were of a regular spherical shape with satisfactory results in terms of the size and size distribution.
The comparison of the dissolution profiles of microspheres in different media shows that microspheres produce a retarding effect in pH 6.8
buffer. Taste evaluation studies confirmed that microspheres of PDL having a drug to polymer ratio of 1: 10 are tasteless and these were
further used for formulation into ODTs. Compression of microspheres resulted in breaking of a fraction of the microspheres but this did
not adversely affect the taste. Conclusion: Effective taste-masking was achieved for PDL using the technique of microencapsulation and
ODTs of acceptable characteristics were obtained by disintegrant addition and direct compression.

Keywords: Taste masking; Orally disintegrating tablets; Prednisolone; Microspheres; Solvent evaporation; pH sensitive polymer
_____________________________________________________________________________________________________________

1. Introduction
Asthma, an inflammatory disease of the airways, is the
most common chronic disease of childhood. Children
reported to have had asthma at some time in their lives
in the Indian subcontinent account for 6.1% of the 13–14
year age group and 5.2% of the 6–7 year age group [1].
A worldwide increase in the prevalence of asthma is
being reported with an increase at rate of 0.28% per
year in the 13–14 year age group and by 0.18% per year
in the 6–7 year age group [1]. Prednisolone effectively
controls the inflammation by inhibition of T cell function [2]
and, thus, provides good control of asthma. Well contro-
lled asthma allows normal growth in children as asthma
__________
*Corresponding author. Address: Department of Pharmaceutics,
Committee for Higher Education Guidance, Seth G. L. Bihani S.
D. College of Technical Education, Sri Ganganagar, Rajasthan,
India. Tel.: +91-154-2466777; Fax: +91-154-2466774.
E-mail: vikas.pharmaceutics@gmail.com
itself retards the growth [3]. Despite the side effects,
oral prednisolone is a treatment of choice due to its
advantages of reliability, simplicity, convenience, and
low cost [4]. It can be used for the treatment of acute,
chronic and moderately severe asthma in adults as well
as children [5, 6]. Moreover, it is an alternative for child-
ren unable to use a metered inhaler. The main problem
with the prednisolone formulations is their extremely
bitter taste, a critical factor as far as compliance is
concerned. Studies have shown that prednisolone taste-
masked or flavored formulations are better tolerated than
crushed tablets in the treatment of acute severe asthma
in children [7].
Various taste-masking technologies have been exten-
sively reviewed [8-10]. Solvent evaporation is a relative-
ly simple and convenient method for the preparation of
taste-masked microspheres. The drug particles are
surrounded by a polymer which prevent leaching of the
drug into the saliva but allow the release of the drug in

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 Taste-masked orally disintegrating tablets of prednisolone/Asian Journal of Pharmaceutical Sciences 2007, 2 (6): 227-238
the stomach. The most widely used solvent systems in
solvent evaporation process are methylene chloride/
water [11] and acetone/light liquid paraffin [12-15]. This
technology has been applied to mask the bitter taste of
antibiotics such as bacampicilin [12, 16], pseudoephe-
drine [11] and cefuroxime axetil [14].
In the present work, prednisolone (PDL) was micro-
encapsulated by the solvent evaporation method using
Eudragit E100 to mask the taste of the drug. Eudragit
E100 [poly(butyl methacrylate, (2-dimethyl aminoethyl)
methacrylate, methyl methacrylate) 1: 2: 1] (Rohm Gm-
bH), is a cationic copolymer with an average molecular
weight of about 150,000. It becomes water soluble via
salt formation with acids, thus providing gastro-soluble
film coatings. Eudragit E films swell and are permeable
in water and buffer solutions above pH 5. At salivary
pH, the polymer is insoluble in water but permeable.
Eudragit E100 prevents the release of drug in the mouth
and thus it prevents the bitter taste sensation. Moreover,
its gastro-soluble nature allows the release of PDL in
the gastric environment. Therefore, it does not retard
the release of PDL from the formulation to an extent
that may affect its bioavailability. Microspheres, micro-
crystalline cellulose, disintegrants and other excipients
are mixed and ODTs were prepared by the direct com-
pression method.
2. Materials and methods
2.1. Materials
The materials used were: prednisolone (obtained as a
gift from Arbro Pharmaceuticals, Delhi, India), eudragit
E100 (Rohm Pharma, Germany), light liquid paraffin (Loba
Chemie, Bombay), acetone (Qualigens Fine Chemicals,
Mumbai), magnesium stearate (kindly supplied by Uni-
chem, New Delhi), microcrystalline cellulose (Avicel
PH 102, FMC, Belgium), croscarmellose sodium (Vivasol
Type A, J. Rettenmaier & Sohne, Rosenberg, Germany),
sodium starch glycollate (Vivastar P5,000, A. J. Retten-
maier & Sohne, Rosenberg, Germany), L-hydroxypropyl-
cellulose (Type LH11, Shin Etsu, Japan), cross linked
polyvinylpyrollidone (Polyplasdone XL, ISP Pharma),
aspartame (Ajinomoto Co., Inc., Japan), sodium chlor-
228
ide (Ranbaxy, New Delhi), menthol (All-Wells Chemi-
cals, Chandigarh), orange dry mix flavor (Lux flavors,
Chennai), and color sunset yellow (Arun Chemical
Industries, New Delhi).
2.2. Compatibility studies
2.2.1. Preparation of samples for thermal stress testing
All ingredients had been previously passed through a
sieve number 60 before the start of the study to ensure the
uniform mixing of drug and excipients. Avicel PH101,
L-HPC, sodium starch glycollate, and Eudragit E100
were separately placed in vials and blended with PDL
(1: 1 ratio) without added water. Stressed samples were
covered with aluminium foil containing pores. Stressed
samples were stored at 40˚C temperature & 75% relative
humidity (RH) in stability chambers for 4 weeks. In a
similar fashion, another set of samples (control) were
prepared, screw capped and stored at 5˚C in the refriger-
ator. A specific quantity of each ingredient was weighed
separately and monitored to note any change in the
physical and chemical characteristics.
2.2.2. Thermal analysis of the samples
Thermal analysis was carried out with the help of DSC
equipment (DSC821e Mettler Toledo) calibrated using
indium as a standard with a melting point (Tfus) of
156.63˚C and a calibration energy ∆fus of 28.89 J/g. The
temperature was increased from 25˚C to 300˚C at a heat-
ing rate of 10˚C/min under a flow of nitrogen (80 ml/min).
From each stressed sample and control sample vials,
approximately 5 mg of the sample was weighed and
subjected to DSC.
2.3. Preparation of microspheres
Microspheres were prepared by the solvent evapora-
tion method previously reported and modified for our
purpose [14, 16]. Eudragit E100 and PDL were co-
dissolved in acetone followed by dispersion of magne-
sium stearate in polymer drug solution. The dispersion
was poured slowly into light liquid paraffin at a low
 Taste-masked orally disintegrating tablets of prednisolone/Asian Journal of Pharmaceutical Sciences 2007, 2 (6): 227-238

stirring speed. After complete addition, the speed was 2.5. Drug content determination in microspheres
increased and the stirring rate was maintained for 8 h
until all the acetone evaporated. n-Hexane was added Microspheres (50 mg) were dissolved in 10 ml
to the system for hardening of the microspheres and 0.07 mol/l HCl by vigorous shaking and the volume
to accelerate settling. Microspheres were separated by was made up to 25 ml. The solution was further diluted
decantation following filtration. Microspheres were then with 0.07 mol/l HCl (1 ml diluted to 10 ml) and the
washed with n-hexane and the washed microspheres absorbance was determined spectrophotometrically (Per-
were dried in an oven maintained at 37˚C for 24 h. kin Elmer Lambda 20 UV Visible Spectrophotometer).
Dried microspheres were stored at room temperature. The PDL content of the microspheres was calculated
The formulation parameters and process parameters for using a standard calibration curve.
different batches of microspheres are given in Table 1.
2.6. Micromeritics of microspheres
2.4. Percentage yield determination
The size distribution and average size of the micro-
After complete drying of microspheres, the percentage spheres were determined by sieve analysis using British
yield was determined by the formula given below. standard sieves (BSS) mounted on a sieve shaker unit.
Weight of the dried microspheres
_______________________________________________
Yield% = ×100
Weight of (PDL + Eudragit E 100 + magnesium stearate)

Table 1
Taste-masked PDL microsphere ingredients, process parameters and evaluation.

Microsphere ingredients and process parameters Microsphere evaluation parameters

Formulation
Stirring Beaker Loading PDL
code PDL Eudragit Magnesium Light liquid Acetone Yield Diameter
speed volume efficiency loading
(mg) E100 (g) stearate (g) paraffin (ml) (mg) (%) (µm)
(r/min) (ml) (%) (%)
VMP/01A 200 2 0.2 2000 250 80 20 79.8 360 81.5 8.5
VMP/02A 100 2 0.1 2000 250 40 10 80.9 ― 81.6 8.4
VMP/03A 200 2 0.2 2000 250 80 20 80.3 299.1 80.7 8.4
VMP/04A 200 2 0.2 2000 250 80 20 79.0 258.6 79.8 8.4
VMP/05A 400 4 0.4 2000 250 150 40 80.0 270.6 79.8 8.3
VMP/06A 1500 15 1.5 4000 1000 500 150 84.2 288.9 85 8.4
VMP/7A 1500 15 1.5 4000 1000 500 150 80.8 307.5 85.7 8.8
VMP/8A 1500 15 1.5 4000 1000 500 150 78.3 338.4 78.1 8.3
VMP/9A 1500 15 1.5 4000 1000 500 150 78.7 333.3 77.9 8.3
VMP/10A 1500 15 1.5 4000 1000 500 150 78.6 329.1 77.9 8.3
VMP/01X 0 15 1.5 4000 1000 500 200 ― ― ― ―
RVMP/01 750 11.25 1 3000 500 250 150 79.4 290.7 85.1 6.2
RVMP/02 750 3.75 0.75 3000 500 250 100 85.6 235.3 85.3 14.2
VMP/OPT/01 1500 15 1.5 4000 1000 500 200 82.1 270.9 84.1 8.5
VMP/OPT/02 1500 15 1.5 2000 1000 500 200 Batch failed
VMP/OPT/03 1500 15 1.5 4000 1000 500 100 82.9 353.3 81.5 8.2
VMP/OPT/04 1500 15 0.8 4000 1000 500 200 74.7 361 75.1 8.4

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2.7. Microscopic evaluation
Microspheres of different batches were observed at
magnifications of × 100 times and × 250 under a Leika
photomicroscope (Leitz Labor Lux S, Germany) fitted
with an MPS 52 camera.
2.8. In vitro release studies
In vitro drug release studies were carried out using
USP XXIV dissolution apparatus II (Model, TDT-06T,
Electrolab, Mumbai, India). Accurately weighed PDL
microspheres were added to the medium under test. The
tests were carried out in pH 1.5 buffer (1,000 ml) and
pH 6.8 buffer (1,000 ml) equilibrated at 37˚C ± 0.5˚C.
The paddles were rotated at 100 r/min. At specific times,
5 ml aliquots of the dissolution medium were withdrawn
and replaced with 5 ml of fresh dissolution medium. The
collected samples were analyzed spectrophotometrically
at 247 nm.
2.9. Taste evaluation of microspheres
A protocol for conducting taste assessment by taste
panel studies was submitted to the Institutional Ethical
Committee of NIPER. Taste assessment studies were
conducted according to the approved protocol on twelve
healthy human volunteers recruited among the students
and staff at NIPER. All the volunteers signed an informed
consent form.
Pure drug (2 mg), PDL microspheres (equivalent to
2 mg prednisolone), and blank microspheres (without
drug) were provided randomly to 12 healthy volunteers
divided into three different groups, each of four volun-
teers. The sequence of the taste testing was different for
each group to avoid any bias pure drug (taste score 4)
and placebo (taste score 1) were used as positive and
negative controls, respectively. Subjects scored the inten-
sity of bitterness by placing the given amount of sample
on the tongue, tasting it for one minute, and thoroughly
rinsing their mouths with water after each sample evalua-
tion. Each volunteer judged the taste of the sample using
a score involving a five point scale which ranged from
0 to 4 (0 = pleasant, 1 = tasteless, 2 = slightly bitter,
230
3 = moderately bitter and 4 = extremely bitter).
2.10. Compression of microspheres
In initial experiments, PDL microspheres were mixed
with different diluents, like avicel, mannitol, advantose
and lactose, and the resulting mixture was compressed
into tablets of 8 mm diameter and weighing 100 mg.
The results obtained from the initial studies were used in
the selection of a suitable diluent for compression of the
microspheres. A prototype of the tablet formulation was
developed. Different batches of tablets were prepared
using different combinations of disintegrants to achieve
ODTs. Microspheres of batches VMP/06A to VMP/10A
(five batches) were pooled and used for preparing ODTs.
The composition of the tablets prepared with pooled
PDL microspheres are given in Table 2. Microspheres
were incorporated into the tablets on the basis the drug
loading so as to give the required dose of 10 mg/tablet.
The PDL microspheres were blended along with the
other excipients (super-disintegrants, sweeteners, flavors,
and lubricants) and processed to allow direct compre-
ssion tabletting in a single punch tablet machine (Model:
CMS H/437/96, Cadmach, Ahmedabad, India).
2.11. Evaluation of tablets
2.11.1. Determination of tablet crushing strength
The compression force applied diametrically to crush
the tablet was determined in KiloPascal (KP) using an
Erweka hardness tester (Model TBH 220, Erwka GmbH,
Heusenstamm).
2.11.2. Determination of tablet friability
Tablet friability was reported as the percentage weight
loss from ten tablets after 100 rotations in a friabilator
(Model EF-2, Electrolab, Mumbai, India).
2.11.3. Measurement of disintegration time
A single tablet was placed in the mouth to determine in
vivo disintegration time of the tablet. As soon as it disin-
 Taste-masked orally disintegrating tablets of prednisolone/Asian Journal of Pharmaceutical Sciences 2007, 2 (6): 227-238

tegrated it was spat out and the disintegration time was
recorded [17, 18]. The in vitro disintegration time was
determined in 10 ml DM water in a 50 ml glass beaker.
2.11.4. Drug content analysis
Five tablets were crushed to a powder and powder
equivalent to 10 mg PDL was taken and extracted with
0.07 mol/l HCl. After suitable dilution, the drug content
was analyzed by UV spectrophotometry.
HCl and pH 6.8 buffer. A USP XXIV Type II (Model,
TDT-06T, Electrolab, Mumbai, India) apparatus was
used. The speed of rotation (100 r/min), temperature of
the bath (37.0˚C ± 0.5˚C), and the volume of the dissolu-
tion medium (1,000 ml) were kept constant throughout
the study. At predetermined time intervals, 5 ml of the
samples was withdrawn and the samples were immedi-
ately analyzed or refrigerated until analyzed. The samples
were then diluted and the concentrations determined by
spectrophotometry using the calibrated standard curve.

2.11.5. Dispersion test 3. Results and discussion

Uniformity of dispersion was checked according to 3.1. Compatibility studies

the procedure in the Indian Pharmacopoeia [19]. Two
tablets were placed in 100 ml water (at 25˚C in a beaker).
The tablets were allowed to disintegrate and the disper-
sion was stirred with a glass rod until a smooth dispersion
was obtained. The dispersion was passed through a
710 µm sieve (No. 22) and the sieve screen was checked
for any material retained.
2.11.6. Dissolution studies
The drug release from the tablets was evaluated by
carrying out in vitro dissolution studies in 0.07 mol/l
No color change or difference in color in the stress
samples and control samples was observed during or
after a 4-week storage period, indicating the absence of
any incompatibility between the mixture components.
The DSC trace of PDL shows one endothermic peak at
242.94, which is associated with the melting of PDL.
There was no change in the peak of PDL when it was
subjected to stress conditions for 4 weeks (peak at 236.80),
indicating the stability of drug under these conditions.
In the DSC of Eudragit E100 and PDL control and
stress mixtures, the changes in the endothermic peak

Table 2
Compositions of prepared ODTs.
Amount (%, w/w)
Ingredients VMP/ VMP/ VMP/ VMP/ VMP/ VMP/ VMP/ VMP/
TAB/11 TAB/12 TAB/13 TAB/14 TAB/15 TAB/16 TAB/17 TAB/18
PDL Microspheres 30 30 30 30 30 30 30 30
Avicel PH 102 45 45 45 45 45 45 41 41
L-HPC 10 10 10 ― ― ― 10 10
Sodium starch glycollate ― 5 ― ― 7.5 10 ― ―
Croscarmellose sodium 5 ― ― 5 7.5 ― ― ―
Polyplasdone XL ― ― 5 10 ― 5 5 5
Aspartame 3 3 3 3 3 3 5 5
Menthol 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1
Sodium chloride 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5
Flavor 4.4 4.4 4.4 3.9 4.1 4.4 6.2 6.2
Aerosil 2 2 2 2 2 2 2 2
Color (Sunset yellow) ― ― ― 0.50 0.33 ― 0.25 0.25

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of the PDL were well preserved with little change in
sharpening, broadening or shifting towards a lower tem-
perature (Fig. 1). These slight changes in the melting
endotherm of the drug may be attributed to the mixing
process, which lowers the purity of each component in
the mixture, thus resulting in slightly broader and lower
melting points, but not truly representing any incom-
patibility [20].
3.2. Preparation of microspheres
Acetone and liquid paraffin (i.e., the polymer solvent
and encapsulating medium, respectively) are poorly
miscible, since acetone has a dielectric constant of 20.7
and liquid paraffin one of about 2) [21]. Therefore,
acetone has a poor compatibility with liquid paraffin,
dispersing a core substance (PDL) in the resulting
solution. Once the desired oil phase droplet size and
emulsion stability was obtained, the system was stirred
at a constant rate for a sufficient time to allow solvent
evaporation. Most of the acetone disappeared by eva-
poration. Evaporation was allowed to take place in an
open system. The amount of the liquid paraffin to be
used as the encapsulating medium was found to be 4 to
15 times that of the dispersion liquid of the core sub-
stance in the polymer solution; if it is too small, the
capsules easily adhere to each other and form lumps
while, if it is too large, the production and recovery of
the capsules become complicated [21]. We were able to
obtain free flowing microspheres even at a light liquid
paraffin: acetone ratio of 2.5. Magnesium stearate is
widely used to prevent electrification and flocculation in
the preparation of microcapsules [13, 16]. Satisfactory
results were obtained and spherical solid PDL micro-
capsules could be prepared by adding a small amount
of magnesium stearate (1: 1 ratio with the drug).
3.3. Percentage yield and drug content
High yields of free flowing, non-aggregated micro-
spheres were obtained. For final five batches prepared
under the same conditions the percentage yield obtained
was 80.12% ± 2.47% (mean ± SD). The loading efficiency
was 77.88 to 85.74 for microspheres with PDL-Eudragit
232
E100 in a ratio of 1:10 while the loading efficiency
for PDL-Eudragit E100 in ratios of 1: 5 and 1: 10 were
85.31 and 85.09, respectively. The yield, percentage
loading and loading efficiency for different batches of
microspheres are given in Table 1.
3.4. Micromeritics of microspheres
The average diameter (Dav) of microspheres determined
by sieve analysis is given in Table 1. On increasing the
stirring rate, the mean diameter of the microspheres was
found to decrease. A drastic reduction in stirring speed
resulted in a batch failure (e.g., VMP/OPT/02). The size
distribution of microspheres prepared under identical
conditions is represented by the histogram in Fig. 2.
3.5. Microscopic evaluation
Photomicrographs of PDL microspheres of several
batches are presented in Fig. 3. The effect of microsphere
size on the sphericity is shown in Fig. 4. All microspheres
appeared porous in nature and the sphericity of the micro-
spheres varied with the size and from batch to batch.
Microspheres were spherical in the size range of
355–710 µm (fraction # 22/44) and 250–355 µm (# 44/60,
major fraction) and microspheres of other sieve fractions
180–250 µm (# 60/85) and 150–180 µm (# 85/100) were
not perfect spheres. A PDL: Eudragit E100 ratio of 1: 10
resulted in the best spherical microspheres. Other ratios,
1: 5 and 1: 15, resulted in asymmetric microsphere (Fig. 5).
A reduction in the volume of acetone for preparing the
drug polymer solution produced aggregated micro-
spheres. The impressions produced by microspheres
sticking can be seen in Fig. 6 (c).
Magnesium stearate acts as a deflocculating agent in
the preparation of microspheres by solvent evaporation.
Addition of a low amount of magnesium stearate to the
dispersion media results in agglomeration of micro-
spheres. The sphericity of microspheres was also reduced
when quantity of magnesium stearate was reduced by
half. Formulation of microspheres also reduces the
microsphere sphericity. Completely spherical micro-
spheres were obtained for batch VMP/OPT/01 [Fig. 6(a)
and Fig. 6(b)]. Thereafter, all batches were prepared
 Taste-masked orally disintegrating tablets of prednisolone/Asian Journal of Pharmaceutical Sciences 2007, 2 (6): 227-238

PDL (C)

PDL (S)

Polymer Z
20 mW

Polymer Z + PDL (C)

Polymer Z + PDL (S)

50 100 150 200 250 300 350 ˚C

0 5 10 15 20 25 30 35 min
Fig. 1. DSC thermograms of PDL with Eudragit E100 (polymer Z). The c and s in parenthesis after the name of each drug or mixture
refer to control samples and stressed samples respectively.

80

70

60
Percentage (%)

50

40

30

20

10

0
18/22 22/44 44/60 60/85 85/100 100/120 120/150
Sieve fraction
Fig. 2. Histogram representing the size distribution of PDL microspheres. Each value represents a mean of five determinations with
different batches. Error bars represent the standard error of mean.

(a) (b) (c)

Fig. 3. Photomicrographs of different batches of PDL microspheres (magnification 100 ×). (a) Batch VMP02A; (b) Batch VMP03A; (c)
Batch VMP05A.

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(a) (b)
Fig. 4. Photomicrographs showing the shape of microspheres of different sizes of PDL microspheres (magnification 100 ×). (a) Sieve
Fraction #22/44; (b) Sieve Fraction #85/100.

(a) (b)
Fig. 5. Photomicrographs of PDL microspheres with different drug loading showing the effect of drug loading on the shape of
microspheres (magnification 100 ×). (a) PDL to Eudragit E100 ratio 1:15; (b) PDL to Eudragit E100 ratio 1:5.

(a) (b)

(c) (d)
Fig. 6. Photomicrographs of PDL microspheres prepared using the optimizing process parameters. (a) Batch VMP/OPT/01 (magnification
100 ×); (b) Batch VMP/OPT/02 (magnification 250 ×); (c) Batch VMP/OPT/03 (magnification 100 ×); (d) Batch VMP/OPT/04
(magnification 100 ×).

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under the same formulation and processing variables as
those used in VMP/OPT/01.
3.6. Dissolution studies with microspheres
Dissolution studies of PDL microspheres (Batch VMP/
07A) were performed in two different pH media (pH 1.5
hydrochloric acid buffer and pH 6.8 phosphate buffer).
The dissolution profiles of these studies are given in Fig. 7.
Eudragit E100 is soluble in an acidic environment by
formation of salts. Therefore, the drug is released from
the microspheres very rapidly in pH 1.5 medium. Appro-
ximately 90% of the drug was released within 10 min.
Drug release in pH 6.8 buffer was comparatively slower
than that in pH 1.5 medium. About 31.34% PDL was
released in 10 min in pH 6.8 medium. Eudragit E100
is insoluble in media with a pH greater than 5 but it
becomes permeable and allows the release of PDL.
The gastric emptying time ranges from 32–87 min in
fasted states for particles with a size in the micron range
and the corresponding value is 34–75 min in fed state [22].
The dissolution profile in hydrochloric buffer pH 1.5
indicated that > 94% of the drug was released from the
microspheres after 30 min. Therefore, it is expected that
as soon as the polymer dissolves in the acidic contents
of stomach, the drug will be release in the stomach and
then absorbed from the gastrointestinal tract.
3.7. Taste evaluation of microspheres
Taste evaluation results for microspheres with different
drug to polymer ratios are given in Table 3. Microspheres
having a drug: polymer ratio of 1: 10 and 1: 15 were
tasteless to most of the volunteers. Four volunteers rated
microspheres with a drug polymer ratio 1: 10 moderately
bitter. A further increase in polymer did not significantly
affect the taste of the microspheres as three volunteers
reported a moderately bitter taste when the drug polymer
ratio was kept at 1: 15. Microspheres having a 1: 10 drug
polymer ratio were chosen for development of ODTs.
3.8. Preparation and evaluation of ODTs
In several initial experimental runs, the diluent avicel
235
was found to be the most suitable and this was used for
the compression of microspheres without significant
damage (breaking or cracking) to the microspheres.
Other, diluents such as mannitol, advantose and lactose,
were these produced tablets with damaged microspheres.
Formulations containing avicel as the diluent were less
susceptible to pressure effects while capable of accept-
ing larger quantities of microcapsules. A prototype com-
position for compression of microspheres was developed
based on these preliminary results. L-HPC and cross
linked PVP in combination produced the fastest disinte-
grating tablets with an in vitro disintegration time of 15 s
and a time 25 s for disintegration in saliva (mouth).
Tablets prepared from the microspheres were evaluated
with regard to various parameters and the results are
given in Table 4. All of the prepared batches passed the
dispersion test. The final composition of formulations
was decided on the basis of the disintegration time of
tablets. Accordingly, the final batch was prepared and
evaluated for taste.
3.9. Dissolution studies
Dissolution studies of prepared tablets were conducted
in pH 6.8 buffer. The drug release from in-house tablets
was retarded at a salivary pH of 6.8. but the release of
PDL from the marketed product (Wysolone tablets) was
immediate. The comparative dissolution profile is shown
in Fig. 8. The release of PDL from in-house tablets in
pH 1.5 buffer was immediate (Fig. 9). It is proposed
that once the drug is released in the gastric medium it
will remain in the free form and become bioavailable.
Therefore, the release profile obtained proved that the
tablet could provide effective taste-masking characteris-
tics without compromising the bioavailability.
3.10. Taste evaluation of ODTs
Eight out of twelve volunteers rated the tablets pleasant
while the others reported a slightly bitter taste (Table 5).
The slightly bitter taste could be due to some crushed and
broken microspheres, which released drug rapidly in the
oral cavity. A slight grittiness was also reported which
could be due to the insoluble nature of the Eudragit E100
 Taste-masked orally disintegrating tablets of prednisolone/Asian Journal of Pharmaceutical Sciences 2007, 2 (6): 227-238

Table 3
Taste panel scores for taste assessment of microspheres.
PDL microspheres Blank
Volunteer code Volunteer group PDL
D: P = 1:5 D: P = 1:5 D: P = 1:15 microspheres

100964 I 4 2 2 1 1
189767 I 4 3 2 1 1
130063 I 3 1 2 2 1
969067 I 4 2 1 1 1
989563 II 4 2 1 1 1
39865 II 4 2 1 2 1
920168 II 4 3 1 2 1
919468 II 4 2 1 1 1
989564 III 4 1 1 1 1
209265 III 4 3 2 1 1
980163 III 4 3 1 1 1
149762 III 4 2 1 1 1

Table 4
Evaluation of prepared ODTs.
VMP/ VMP/ VMP/ VMP/ VMP/ VMP/ VMP/ VMP/
Parameters
TAB/11 TAB/12 TAB/13 TAB/14 TAB/15 TAB/16 TAB/17 TAB/18
Friability (%) 1.54 1.99 2.10 1.80 2.92 1.60 1.56 1.80
Average hardness (kP) 8.18 5.34 6.22 5.70 4.06 5.96 5.66 5.82
Assay (%) 100.7 98.1 100.9 103.1 101.4 98.2 102.0 107.4
In vivo (Oral) DT (s) 60 80 25 30 40 60 28 32
In vitro DT (s) 20 22 15 20 25 25 18 18

120

100
Cumulative release of PDL (%)

80

60

40

in pH 1.5 hydrochloric acid buffer

20
in pH 6.8 phosphate buffer

0
0 10 20 30 40 50 60 70
Time (min)
Fig. 7. Dissolution profiles of PDL taste-masked microspheres in pH 1.5 hydrochloric acid buffer and pH 6.8 phosphate buffer. Each
value represents an average of three determinations. Error bars represent the standard error of the mean.

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 Taste-masked orally disintegrating tablets of prednisolone/Asian Journal of Pharmaceutical Sciences 2007, 2 (6): 227-238

Table 5
Taste panel scores for taste-masked PDL ODTs.

Volunteer code Volunteer group Marketed tablets PDL in-house formulation Placebo tablets
989564 I 3 0 0
919468 I 4 0 0
980163 I 4 0 0
209265 I 4 2 2
920168 II 4 0 0
39865 II 4 0 0
130063 II 4 2 0
189767 II 4 2 0
100964 III 4 0 0
149762 III 4 2 0
989563 III 4 0 0
969067 III 4 0 0

120 105

90
Cumulative release of PDL (%)

100
Cumulative release of PDL (%)

75
80
60
60
45
in pH 1.5
40 hydrochloric acid buffer
30
In-house PDL ODTs
20 Wysolone tablets 15

0 0
0 15 30 45 60 0 20 40 60 80 100 120
Time (min) Time (min)
Fig. 8. Comparison of the dissolution profiles of in-house PDL Fig. 9. Dissolution profile of PDL ODTs in pH 1.5 hydrochloric
ODTs and Wysolone tablets in pH 6.8 phosphate buffers. Each acid buffer. Each value represents an average of three determina-
value represents an average of three determinations. Error bars tions. Error bars represent the standard error of the mean.
represent the standard error of the mean.

and other water insoluble excipients. Three out of twelve
volunteers rated ODTs moderately bitter while the
remaining volunteers found them pleasant tasting. On
comparison of the results for the taste evaluation of
microspheres, it was concluded that the addition of
sweetener to ODTs further suppressed the bitter taste
and provided a pleasant sweet taste. One volunteer (Volun-
teer code 209265) rated ODT and the placebo tablet
moderately bitter and it was rather difficult to explain
why the placebo tablet was rated moderately bitter. From
this result it was concluded that there was no difference
in the rating of taste between the placebo tablet and
ODT. Effective taste-masking was achieved for PDL
using the microencapsulation technique. It is suggested
that this technique may be used for masking the bitter
taste of other drugs. Other dosage forms like granules,
dry syrup or suspensions or non aqueous suspensions
may also be formulated in this way.

237
 Taste-masked orally disintegrating tablets of prednisolone/Asian Journal of Pharmaceutical Sciences 2007, 2 (6): 227-238
4. Conclusions
Eudragit E microspheres loaded with PDL can be
easily prepared by the use of the solvent evaporation
method. The procedure gave satisfactory results in terms
of the size, shape, and size distribution of the micro-
spheres. The dissolution experiment showed that the
release of drug is retarded in pH 6.8 media and, therefore,
the drug is not expected to be released in saliva after
oral administration. Taste evaluation of the microspheres
confirmed this. ODTs containing taste-masked PDL
microspheres, disintegrants, sweetener and other exci-
pients were prepared by the direct compression method.
Characterization of the ODTs confirmed that adequate
taste masking and faster disintegration could be achieved
for PDL. Novel taste-masked formulations and ODTs
would be helpful in increasing drug compliance in child-
ren and other special populations.
Acknowledgements
We gratefully acknowledge the financial assistance,
chemicals and laboratory facilities provided by NIPER.
The authors are also grateful for the gift of prednisolone
by Arbro Pharmaceuticals, New Delhi. Ms Rohm Pharma
GmbH, Dramstadt was very kind in providing us with
Eudragit E100. Ajinomoto Co. Inc., Japan kindly donated
aspartame and croscarmellose sodium (Vivasol Type A)
and sodium starch glycollate (Vivastar P5,000) were
provided by Ms. A. J. Rettenmaier & Sohne, Rosenberg,
Germany. We are also grateful to all these excipient
manufacturers for their generous support by providing
gift samples for our research. Thanks are also due to
Vikas Grover, Central Instrumentation Laboratory,
NIPER, for his help in carrying out the DSC analysis.
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